title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of VS-6063 in Subjects With Malignant Pleural Mesothelioma

acronym: COMMAND

summary: This study is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study of defactinib (VS-6063) in subjects with malignant pleural mesothelioma (MPM) who have not progressed (confirmed partial response or stable disease) following ≥ 4 cycles of treatment with pemetrexed/cisplatin or pemetrexed/carboplatin. Prior to entry and randomization to the study, each subject must have tumor Merlin status(high or low) established by immunohistochemistry performed at a central laboratory. Subjects will be randomized in a 1:1 ratio to receive oral VS-6063 400 mg twice per day, or matched placebo. Randomization will be stratified by tumor Merlin status (high versus low). Progression will be assessed both locally and by central review using the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1. Subjects will continue to receive treatment until disease progression or other discontinuation criteria are met. Following documentation of nonfatal disease progression, all subjects will be followed for overall survival by telephone contact every 2 months until end of life or the close of the study.

ReferenceCitation: Fennell DA, Baas P, Taylor P, Nowak AK, Gilligan D, Nakano T, Pachter JA, Weaver DT, Scherpereel A, Pavlakis N, van Meerbeeck JP, Cedrés S, Nolan L, Kindler H, Aerts JGJV. Maintenance Defactinib Versus Placebo After First-Line Chemotherapy in Patients With Merlin-Stratified Pleural Mesothelioma: COMMAND-A Double-Blind, Randomized, Phase II Study. J Clin Oncol. 2019 Apr 1;37(10):790-798. doi: 10.1200/JCO.2018.79.0543. Epub 2019 Feb 20.

lead_sponsor: Verastem, Inc.

location_country:
Poland
Spain
Italy
United Kingdom
Australia
New Zealand
Canada
Sweden
United States
France
South Africa
Norway
Belgium
Japan
Netherlands

location_facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

location_facility: Centrum Pulmonologii Ii Torakochirurgii w Bystrej

location_facility: Iatros International / Bloemfontein Medi-Clinic

location_facility: University of California San Francisco Medical Center

location_facility: Canterbury Regional Cancer & Haematology Service

location_facility: Institut Oncològic del Vallés Consorci Hospitalari Parc Tauli

location_facility: Mary Potter Oncology Center, Little Company of Mary Hospital

location_facility: Kent Oncology Centre, Maidstone Hospital

location_facility: Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis

location_facility: Hospital Madrid Norte- Sanchinarro, Centro Integral Oncológico Clara Campal (CIOCC)

location_facility: Princess Alexandra Hospital +61(0)7 3176 5054

location_facility: Universitaire Ziekenhuizen Leuven (University Hospitals Leuven)


type: EudraCT Number

title: An Extension Study to Evaluate the Sustainability of Clinical Benefits, Safety and Tolerability of Secukinumab in Patients With Active Ankylosing Spondylitis

acronym: MEASURE 1 ext

summary: This 3-year extension study aims at making available the treatment with secukinumab in prefilled syringes (PFS) to patients with ankylosing spondylitis who took part in phase III study CAIN457F2305, defined as "core study", as well as to generate additional data on the sustainability of clinical benefits, safety and tolerability during long-term administration of secukinumab.

study_start_date_type: Actual

status: Completed

study_completion_date_type: Actual

study_type: Interventional

design_allocation: Randomized

primary_purpose: Treatment

enrollment_type: Actual

ReferenceType: derived

ReferenceCitation: Baraliakos X, Van den Bosch F, Machado PM, Gensler LS, Marzo-Ortega H, Sherif B, Quebe-Fehling E, Porter B, Gaillez C, Deodhar A. Achievement of Remission Endpoints with Secukinumab Over 3 Years in Active Ankylosing Spondylitis: Pooled Analysis of Two Phase 3 Studies. Rheumatol Ther. 2021 Mar;8(1):273-288. doi: 10.1007/s40744-020-00269-6. Epub 2020 Dec 22.

ReferenceCitation: Tseng JC, Wei JC, Deodhar A, Martin R, Porter B, McCreddin S, Talloczy Z. Secukinumab Demonstrates Sustained Efficacy and Safety in a Taiwanese Subpopulation With Active Ankylosing Spondylitis: Four-Year Results From a Phase 3 Study, MEASURE 1. Front Immunol. 2020 Nov 26;11:561748. doi: 10.3389/fimmu.2020.561748. eCollection 2020.

ReferenceCitation: Kvien TK, Conaghan PG, Gossec L, Strand V, Østergaard M, Poddubnyy D, Williams N, Porter B, Shete A, Gilloteau I, Deodhar A. Secukinumab and Sustained Reduction in Fatigue in Patients With Ankylosing Spondylitis: Long-Term Results of Two Phase III Randomized Controlled Trials. Arthritis Care Res (Hoboken). 2022 May;74(5):759-767. doi: 10.1002/acr.24517. Epub 2022 Mar 10.

ReferenceCitation: Baraliakos X, Braun J, Deodhar A, Poddubnyy D, Kivitz A, Tahir H, Van den Bosch F, Delicha EM, Talloczy Z, Fierlinger A. Long-term efficacy and safety of secukinumab 150 mg in ankylosing spondylitis: 5-year results from the phase III MEASURE 1 extension study. RMD Open. 2019 Sep 3;5(2):e001005. doi: 10.1136/rmdopen-2019-001005. eCollection 2019.

ReferenceCitation: Braun J, Baraliakos X, Deodhar A, Poddubnyy D, Emery P, Delicha EM, Talloczy Z, Porter B. Secukinumab shows sustained efficacy and low structural progression in ankylosing spondylitis: 4-year results from the MEASURE 1 study. Rheumatology (Oxford). 2019 May 1;58(5):859-868. doi: 10.1093/rheumatology/key375.

ipd_sharing: Undecided

ipd_sharing_description:
Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

lead_sponsor: Novartis Pharmaceuticals

location_country:
Taiwan
United Kingdom
Italy
Russian Federation
Mexico
Netherlands
Canada
United States
France
Peru
Turkey
Belgium
Germany
Bulgaria

intervention_type: Biological

lead_sponsor_type: industriel

status_simplified: Completed


title: Long-term Extension Study of BOTOX® in the Treatment of Urinary Incontinence Due to Neurogenic Detrusor Overactivity in Patients 5 to 17 Years of Age

lead_sponsor: Allergan

source: euctr

design_allocation: Non-Randomized

location_country:
Poland
Italy
Canada
France
United States
Turkey
Belgium
Czechia

location_facility: Copernicus Podmiot Leczniczy Sp. z o. o. Kliniczny Oddział Chirurgii i Urologii Dzieci i Młodzieży GUMed

location_facility: St. Louis Children's Hospital Division of Urology

location_facility: Children's Hospital of Wisconsin Department of Pediatric Urology

location_facility: Cincinnati Children's Hospital Medical Center Cincinnati Center for Clinical Research and Outpatient Clinic

location_facility: CHU de Limoges - HÃ´pital MÃ¨re et l'Enfant

location_facility: William Beaumont Hospital Research Institute

location_facility: University of Alabama at Birmingham Division of Urology Research Office

location_facility: Ann & Robert H. Lurie Children's Hospital of Chicago

summary: This study will evaluate the long-term safety and efficacy of onabotulinumtoxinA (botulinum toxin Type A; BOTOX®) for the treatment of urinary incontinence due to neurogenic detrusor overactivity in participants who successfully completed Study 191622-120 (NCT01852045).


title: Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis (TOPAS Study Phase III)

summary:
Low-flow, low-gradient (LF-LG) aortic stenosis (AS) may occur with depressed (i.e. Classical LF; CLF) or preserved (i.e. Paradoxical LF; PLF) LV ejection fraction (LVEF) and both situations are amongst the most challenging encountered in patients with valvular heart disease. Although, CLF-LG AS is recognized has an important clinical entity, current ACC/AHA-ESC guidelines however do not provide precise recommendations for clinical management of these patients . PLF-LG AS is a new entity recently described by our group, which is characterized by more pronounced LV concentric remodeling with smaller LV cavity size and a restrictive physiology leading to impaired LV filling, altered myocardial function, and a low-flow state. Up to recently, this entity was often misdiagnosed, leading to underestimation of AS severity and inappropriate delays for aortic valve replacement surgery (SAVR). The two main challenges in patients with CLF- or PLF- LG AS are to distinguish between a true-severe (TS) versus a pseudo-severe (PS) stenosis and to accurately quantify the extent of myocardial impairment. Unfortunately, the traditional resting and stress echocardiographic parameters currently used to assess the severity of valvular and myocardial dysfunction in patients with LF-LG AS are far from being optimal, and as a consequence, quantification of disease severity and therapeutic management may not be appropriate in a substantial proportion of these patients.

THE GENERAL OBJECTIVES of the TOPAS study are to develop and validate new parameters and biomarkers to improve the assessment of stenosis severity and myocardial impairment, the risk-stratification, and the clinical decision making in patients with LF-LG AS and to assess the impact of the different therapeutic strategies on patient outcomes.

status: Recruiting

study_completion_date_type: Anticipated

study_type: Observational

time_perspective: Prospective

enrollment_type: Anticipated

ReferenceType: background

ReferenceCitation: Blais C, Dumesnil JG, Baillot R, Simard S, Doyle D, Pibarot P. Impact of valve prosthesis-patient mismatch on short-term mortality after aortic valve replacement. Circulation. 2003 Aug 26;108(8):983-8. Epub 2003 Aug 11.

ReferenceCitation: Mohty D, Dumesnil JG, Echahidi N, Mathieu P, Dagenais F, Voisine P, Pibarot P. Impact of prosthesis-patient mismatch on long-term survival after aortic valve replacement: influence of age, obesity, and left ventricular dysfunction. J Am Coll Cardiol. 2009 Jan 6;53(1):39-47. doi: 10.1016/j.jacc.2008.09.022.

ReferenceCitation: Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P. Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival. Circulation. 2007 Jun 5;115(22):2856-64. Epub 2007 May 28.

ReferenceCitation: Hachicha Z, Dumesnil JG, Pibarot P. Usefulness of the valvuloarterial impedance to predict adverse outcome in asymptomatic aortic stenosis. J Am Coll Cardiol. 2009 Sep 8;54(11):1003-11. doi: 10.1016/j.jacc.2009.04.079.

ReferenceCitation: Pibarot P, Dumesnil JG. Low-flow, low-gradient aortic stenosis with normal and depressed left ventricular ejection fraction. J Am Coll Cardiol. 2012 Nov 6;60(19):1845-53. doi: 10.1016/j.jacc.2012.06.051. Epub 2012 Oct 10. Review.

ReferenceCitation: Dumesnil JG, Pibarot P, Carabello B. Paradoxical low flow and/or low gradient severe aortic stenosis despite preserved left ventricular ejection fraction: implications for diagnosis and treatment. Eur Heart J. 2010 Feb;31(3):281-9. doi: 10.1093/eurheartj/ehp361. Epub 2009 Sep 8. Review.

ReferenceCitation: Dumesnil JG, Pibarot P. Evaluation of aortic stenosis severity: new challenges, new solutions. J Am Soc Echocardiogr. 2011 Sep;24(9):992-4. doi: 10.1016/j.echo.2011.07.011.

ReferenceCitation: Pibarot P, Dumesnil JG. Assessment of aortic stenosis severity: when the gradient does not fit with the valve area. Heart. 2010 Sep;96(18):1431-3. doi: 10.1136/hrt.2010.195149.

ReferenceCitation: Pibarot P, Dumesnil JG. Paradoxical low-flow, low-gradient aortic stenosis adding new pieces to the puzzle. J Am Coll Cardiol. 2011 Jul 19;58(4):413-5. doi: 10.1016/j.jacc.2011.01.057.

ReferenceCitation: Pibarot P, Dumesnil JG. Improving assessment of aortic stenosis. J Am Coll Cardiol. 2012 Jul 17;60(3):169-80. doi: 10.1016/j.jacc.2011.11.078. Review.

ReferenceCitation: Picano E, Pibarot P, Lancellotti P, Monin JL, Bonow RO. The emerging role of exercise testing and stress echocardiography in valvular heart disease. J Am Coll Cardiol. 2009 Dec 8;54(24):2251-60. doi: 10.1016/j.jacc.2009.07.046.

ReferenceCitation: Rodriguez-Gabella T, Nombela-Franco L, Auffret V, Asmarats L, Islas F, Maes F, Ferreira-Neto AN, Paradis JM, Dumont E, Côté M, Jiménez-Quevedo P, Macaya C, Pibarot P, Rodés-Cabau J. Transcatheter Aortic Valve Implantation in Patients With Paradoxical Low-Flow, Low-Gradient Aortic Stenosis. Am J Cardiol. 2018 Aug 15;122(4):625-632. doi: 10.1016/j.amjcard.2018.04.044. Epub 2018 May 17.

ReferenceCitation: Annabi MS, Clisson M, Clavel MA, Pibarot P. Workup and Management of Patients With Paradoxical Low-Flow, Low-Gradient Aortic Stenosis. Curr Treat Options Cardiovasc Med. 2018 May 2;20(6):49. doi: 10.1007/s11936-018-0642-y. Review.

ReferenceCitation: Ribeiro HB, Lerakis S, Gilard M, Cavalcante JL, Makkar R, Herrmann HC, Windecker S, Enriquez-Sarano M, Cheema AN, Nombela-Franco L, Amat-Santos I, Muñoz-García AJ, Garcia Del Blanco B, Zajarias A, Lisko JC, Hayek S, Babaliaros V, Le Ven F, Gleason TG, Chakravarty T, Szeto WY, Clavel MA, de Agustin A, Serra V, Schindler JT, Dahou A, Puri R, Pelletier-Beaumont E, Côté M, Pibarot P, Rodés-Cabau J. Transcatheter Aortic Valve Replacement in Patients With Low-Flow, Low-Gradient Aortic Stenosis: The TOPAS-TAVI Registry. J Am Coll Cardiol. 2018 Mar 27;71(12):1297-1308. doi: 10.1016/j.jacc.2018.01.054.

ReferenceCitation: Annabi MS, Touboul E, Dahou A, Burwash IG, Bergler-Klein J, Enriquez-Sarano M, Orwat S, Baumgartner H, Mascherbauer J, Mundigler G, Cavalcante JL, Larose É, Pibarot P, Clavel MA. Dobutamine Stress Echocardiography for Management of Low-Flow, Low-Gradient Aortic Stenosis. J Am Coll Cardiol. 2018 Feb 6;71(5):475-485. doi: 10.1016/j.jacc.2017.11.052.

ReferenceCitation: Dahou A, Clavel MA, Dumesnil JG, Capoulade R, Ribeiro HB, O'Connor K, Mathieu P, Beaudoin J, Larose É, Rodés-Cabau J, Pibarot P. Impact of AVR on LV Remodeling and Function in Paradoxical Low-Flow, Low-Gradient Aortic Stenosis With Preserved LVEF. JACC Cardiovasc Imaging. 2017 Jan;10(1):88-89. doi: 10.1016/j.jcmg.2016.07.009. Epub 2016 Nov 9.

ReferenceCitation: Dahou A, Toubal O, Clavel MA, Beaudoin J, Magne J, Mathieu P, Philippon F, Dumesnil JG, Puri R, Ribeiro HB, Larose É, Rodés-Cabau J, Pibarot P. Relationship Between QT Interval and Outcome in Low-Flow Low-Gradient Aortic Stenosis With Low Left Ventricular Ejection Fraction. J Am Heart Assoc. 2016 Oct 20;5(10). pii: e003980.

ReferenceCitation: Dahou A, Clavel MA, Capoulade R, Bartko PE, Magne J, Mundigler G, Bergler-Klein J, Burwash I, Mascherbauer J, Ribeiro HB, O'Connor K, Baumgartner H, Sénéchal M, Dumesnil JG, Rosenhek R, Mathieu P, Larose E, Rodés-Cabau J, Pibarot P. Right ventricular longitudinal strain for risk stratification in low-flow, low-gradient aortic stenosis with low ejection fraction. Heart. 2016 Apr;102(7):548-54. doi: 10.1136/heartjnl-2015-308309. Epub 2016 Jan 13.

ReferenceCitation: Dayan V, Vignolo G, Magne J, Clavel MA, Mohty D, Pibarot P. Outcome and Impact of Aortic Valve Replacement in Patients With Preserved LVEF and Low-Gradient Aortic Stenosis. J Am Coll Cardiol. 2015 Dec 15;66(23):2594-2603. doi: 10.1016/j.jacc.2015.09.076.

ReferenceCitation: Le Ven F, Thébault C, Dahou A, Ribeiro HB, Capoulade R, Mahjoub H, Urena M, Nombela-Franco L, Allende Carrera R, Clavel MA, Dumont É, Dumesnil J, De Larochellière R, Rodés-Cabau J, Pibarot P. Evolution and prognostic impact of low flow after transcatheter aortic valve replacement. Heart. 2015 Aug;101(15):1196-203. doi: 10.1136/heartjnl-2014-307067. Epub 2015 May 21.

ReferenceCitation: Dahou A, Magne J, Clavel MA, Capoulade R, Bartko PE, Bergler-Klein J, Sénéchal M, Mundigler G, Burwash I, Ribeiro HB, O'Connor K, Mathieu P, Baumgartner H, Dumesnil JG, Rosenhek R, Larose E, Rodés-Cabau J, Pibarot P. Tricuspid Regurgitation Is Associated With Increased Risk of Mortality in Patients With Low-Flow Low-Gradient Aortic Stenosis and Reduced Ejection Fraction: Results of the Multicenter TOPAS Study (True or Pseudo-Severe Aortic Stenosis). JACC Cardiovasc Interv. 2015 Apr 20;8(4):588-96. doi: 10.1016/j.jcin.2014.08.019. Epub 2015 Mar 26.

ReferenceCitation: Dahou A, Bartko PE, Capoulade R, Clavel MA, Mundigler G, Grondin SL, Bergler-Klein J, Burwash I, Dumesnil JG, Sénéchal M, O'Connor K, Baumgartner H, Pibarot P. Usefulness of global left ventricular longitudinal strain for risk stratification in low ejection fraction, low-gradient aortic stenosis: results from the multicenter True or Pseudo-Severe Aortic Stenosis study. Circ Cardiovasc Imaging. 2015 Mar;8(3):e002117. doi: 10.1161/CIRCIMAGING.114.002117.

ReferenceCitation: Clavel MA, Berthelot-Richer M, Le Ven F, Capoulade R, Dahou A, Dumesnil JG, Mathieu P, Pibarot P. Impact of classic and paradoxical low flow on survival after aortic valve replacement for severe aortic stenosis. J Am Coll Cardiol. 2015 Feb 24;65(7):645-53. doi: 10.1016/j.jacc.2014.11.047.

ReferenceCitation: Mohty D, Boulogne C, Magne J, Pibarot P, Echahidi N, Cornu E, Dumesnil J, Laskar M, Virot P, Aboyans V. Prevalence and long-term outcome of aortic prosthesis-patient mismatch in patients with paradoxical low-flow severe aortic stenosis. Circulation. 2014 Sep 9;130(11 Suppl 1):S25-31. doi: 10.1161/CIRCULATIONAHA.113.007819.

ReferenceCitation: Clavel MA, Côté N, Mathieu P, Dumesnil JG, Audet A, Pépin A, Couture C, Fournier D, Trahan S, Pagé S, Pibarot P. Paradoxical low-flow, low-gradient aortic stenosis despite preserved left ventricular ejection fraction: new insights from weights of operatively excised aortic valves. Eur Heart J. 2014 Oct 7;35(38):2655-62. doi: 10.1093/eurheartj/ehu152. Epub 2014 Apr 21.

ReferenceCitation: Mohty D, Magne J, Deltreuil M, Aboyans V, Echahidi N, Cassat C, Pibarot P, Laskar M, Virot P. Outcome and impact of surgery in paradoxical low-flow, low-gradient severe aortic stenosis and preserved left ventricular ejection fraction: a cardiac catheterization study. Circulation. 2013 Sep 10;128(11 Suppl 1):S235-42. doi: 10.1161/CIRCULATIONAHA.112.000031.

ReferenceCitation: Le Ven F, Freeman M, Webb J, Clavel MA, Wheeler M, Dumont É, Thompson C, De Larochellière R, Moss R, Doyle D, Ribeiro HB, Urena M, Nombela-Franco L, Rodés-Cabau J, Pibarot P. Impact of low flow on the outcome of high-risk patients undergoing transcatheter aortic valve replacement. J Am Coll Cardiol. 2013 Aug 27;62(9):782-8. doi: 10.1016/j.jacc.2013.05.044. Epub 2013 Jun 12.

ReferenceCitation: Clavel MA, Ennezat PV, Maréchaux S, Dumesnil JG, Capoulade R, Hachicha Z, Mathieu P, Bellouin A, Bergeron S, Meimoun P, Arsenault M, Le Tourneau T, Pasquet A, Couture C, Pibarot P. Stress echocardiography to assess stenosis severity and predict outcome in patients with paradoxical low-flow, low-gradient aortic stenosis and preserved LVEF. JACC Cardiovasc Imaging. 2013 Feb;6(2):175-83. doi: 10.1016/j.jcmg.2012.10.015.

ReferenceCitation: Williams TE, O'Day DM, Head WS, Robinson RD. Measurements of antifungal levels in corneal tissue: a simplified bioassay for amphotericin B. Graefes Arch Clin Exp Ophthalmol. 1990;228(6):538-40.

ReferenceCitation: Clavel MA, Burwash IG, Mundigler G, Dumesnil JG, Baumgartner H, Bergler-Klein J, Sénéchal M, Mathieu P, Couture C, Beanlands R, Pibarot P. Validation of conventional and simplified methods to calculate projected valve area at normal flow rate in patients with low flow, low gradient aortic stenosis: the multicenter TOPAS (True or Pseudo Severe Aortic Stenosis) study. J Am Soc Echocardiogr. 2010 Apr;23(4):380-6. doi: 10.1016/j.echo.2010.02.002.

ReferenceType: result

ReferenceCitation: Blais C, Burwash IG, Mundigler G, Dumesnil JG, Loho N, Rader F, Baumgartner H, Beanlands RS, Chayer B, Kadem L, Garcia D, Durand LG, Pibarot P. Projected valve area at normal flow rate improves the assessment of stenosis severity in patients with low-flow, low-gradient aortic stenosis: the multicenter TOPAS (Truly or Pseudo-Severe Aortic Stenosis) study. Circulation. 2006 Feb 7;113(5):711-21.

ReferenceCitation: Clavel MA, Webb JG, Rodés-Cabau J, Masson JB, Dumont E, De Larochellière R, Doyle D, Bergeron S, Baumgartner H, Burwash IG, Dumesnil JG, Mundigler G, Moss R, Kempny A, Bagur R, Bergler-Klein J, Gurvitch R, Mathieu P, Pibarot P. Comparison between transcatheter and surgical prosthetic valve implantation in patients with severe aortic stenosis and reduced left ventricular ejection fraction. Circulation. 2010 Nov 9;122(19):1928-36. doi: 10.1161/CIRCULATIONAHA.109.929893. Epub 2010 Oct 25.

ReferenceCitation: Clavel MA, Fuchs C, Burwash IG, Mundigler G, Dumesnil JG, Baumgartner H, Bergler-Klein J, Beanlands RS, Mathieu P, Magne J, Pibarot P. Predictors of outcomes in low-flow, low-gradient aortic stenosis: results of the multicenter TOPAS Study. Circulation. 2008 Sep 30;118(14 Suppl):S234-42. doi: 10.1161/CIRCULATIONAHA.107.757427.

ReferenceCitation: Bergler-Klein J, Mundigler G, Pibarot P, Burwash IG, Dumesnil JG, Blais C, Fuchs C, Mohty D, Beanlands RS, Hachicha Z, Walter-Publig N, Rader F, Baumgartner H. B-type natriuretic peptide in low-flow, low-gradient aortic stenosis: relationship to hemodynamics and clinical outcome: results from the Multicenter Truly or Pseudo-Severe Aortic Stenosis (TOPAS) study. Circulation. 2007 Jun 5;115(22):2848-55. Epub 2007 May 21.

ReferenceCitation: Burwash IG, Lortie M, Pibarot P, de Kemp RA, Graf S, Mundigler G, Khorsand A, Blais C, Baumgartner H, Dumesnil JG, Hachicha Z, DaSilva J, Beanlands RS. Myocardial blood flow in patients with low-flow, low-gradient aortic stenosis: differences between true and pseudo-severe aortic stenosis. Results from the multicentre TOPAS (Truly or Pseudo-Severe Aortic Stenosis) study. Heart. 2008 Dec;94(12):1627-33. doi: 10.1136/hrt.2007.135475. Epub 2008 Apr 1.

ReferenceCitation: Clavel MA, Webb JG, Pibarot P, Altwegg L, Dumont E, Thompson C, De Larochellière R, Doyle D, Masson JB, Bergeron S, Bertrand OF, Rodés-Cabau J. Comparison of the hemodynamic performance of percutaneous and surgical bioprostheses for the treatment of severe aortic stenosis. J Am Coll Cardiol. 2009 May 19;53(20):1883-91. doi: 10.1016/j.jacc.2009.01.060.

ReferenceCitation: Clavel MA, Rodés-Cabau J, Dumont É, Bagur R, Bergeron S, De Larochellière R, Doyle D, Larose E, Dumesnil JG, Pibarot P. Validation and characterization of transcatheter aortic valve effective orifice area measured by Doppler echocardiography. JACC Cardiovasc Imaging. 2011 Oct;4(10):1053-62. doi: 10.1016/j.jcmg.2011.06.021.

ReferenceCitation: Clavel MA, Dumesnil JG, Capoulade R, Mathieu P, Sénéchal M, Pibarot P. Outcome of patients with aortic stenosis, small valve area, and low-flow, low-gradient despite preserved left ventricular ejection fraction. J Am Coll Cardiol. 2012 Oct 2;60(14):1259-67. doi: 10.1016/j.jacc.2011.12.054. Epub 2012 May 30.

ReferenceCitation: Annabi MS, Côté N, Dahou A, Bartko PE, Bergler-Klein J, Burwash IG, Orwat S, Baumgartner H, Mascherbauer J, Mundigler G, Fukui M, Cavalcante J, Ribeiro HB, Rodès-Cabau J, Clavel MA, Pibarot P. Comparison of Early Surgical or Transcatheter Aortic Valve Replacement Versus Conservative Management in Low-Flow, Low-Gradient Aortic Stenosis Using Inverse Probability of Treatment Weighting: Results From the TOPAS Prospective Observational Cohort Study. J Am Heart Assoc. 2020 Dec 15;9(24):e017870. doi: 10.1161/JAHA.120.017870. Epub 2020 Dec 8.

ReferenceCitation: Dahou A, Clavel MA, Capoulade R, O'Connor K, Ribeiro HB, Côté N, Le Ven F, Rodés-Cabau J, Dumesnil JG, Mathieu P, Pibarot P. B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin for Risk Stratification in Low-Flow, Low-Gradient Aortic Stenosis: A Substudy of the TOPAS Study. JACC Cardiovasc Imaging. 2018 Jul;11(7):939-947. doi: 10.1016/j.jcmg.2017.06.018. Epub 2017 Oct 5.

lead_sponsor: Laval University

location_country:
Austria
Canada
United States
France
Belgium
Germany

location_facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec

intervention_type: Other

lead_sponsor_type: academique

status_simplified: Ongoing


status: Terminated

intervention_type: Drug

title: Phase 1b/2, Multicenter, Open-label Study of Oprozomib and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma

lead_sponsor: Amgen

type: Other Identifier

ReferenceCitation: Hari P, Paba-Prada CE, Voorhees PM, Frye J, Chang YL, Moreau P, Zonder J, Boccia R, Shain KH. Efficacy and safety results from a phase 1b/2, multicenter, open-label study of oprozomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma. Leuk Res. 2019 Aug;83:106172. doi: 10.1016/j.leukres.2019.106172. Epub 2019 Jun 17.

location_country:
United States
France

location_facility: University of Kansas Cancer Center and Medical Pavilion

location_facility: Froedtert Hospital and the Medical College of Wisconsin

location_facility: CHU Hotel Dieu - Service d'Hematologie Clinique

location_facility: CHRU, Hopital Huriez - Department of Hematology

location_facility: Division of Hematology/ Oncology, UNC at Chapel Hill

location_facility: H. Lee Moffitt Cancer Center & Research Institute

summary:
The primary objectives are:

Phase 1b:

To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of oprozomib given orally, once daily, on 2 different schedules.
To evaluate safety and tolerability

Phase 2:

To estimate the overall response rate (ORR).
To evaluate safety and tolerability

status_simplified: Unknown


title: International Long-term Follow-up Study of Patients Implanted With a Portico™ Valve

summary: This study will further assess the performance and safety profile of the commercially available Portico Valve implanted, using the Delivery System and the Loading System, in patients with severe symptomatic aortic stenosis through 5 years of follow-up.

status: Active, not recruiting

ReferenceCitation: Søndergaard L, Rodés-Cabau J, Hans-Peter Linke A, Fichtlscherer S, Schäfer U, Kuck KH, Kempfert J, Arzamendi D, Bedogni F, Asch FM, Worthley S, Maisano F. Transcatheter Aortic Valve Replacement With a Repositionable Self-Expanding Prosthesis: The PORTICO-I Trial 1-Year Outcomes. J Am Coll Cardiol. 2018 Dec 11;72(23 Pt A):2859-2867. doi: 10.1016/j.jacc.2018.09.014. Epub 2018 Sep 24.

ipd_sharing: No

lead_sponsor: Abbott Medical Devices

location_country:
Denmark
Spain
Italy
United Kingdom
Australia
Netherlands
Canada
Lithuania
Switzerland
France
Israel
Belgium
Germany

location_facility: Hospital Clinico Universitario Virgen de Arrixaca

location_facility: Herzzentrum Dresden GmbH Universitatsklinik

location_facility: Morriston hospital-ABM University Health Board

location_facility: Fondazione Toscana Gabriele Monasterio - Ospedale del Cuore

location_facility: Klinikum der Johann Wolfgang Goethe-Universitat Frankfurt

location_facility: Saint John Regional Hospital - New Brunswick Heart Centre

location_facility: Immanuelklinikum Bernau und Herzzentrum Brandenburg

location_facility: Institut de Cardiologie de Quebec (Hospital Laval)

location_facility: Deutsches Herzzentrum Munchen des Freistaates Bayern

location_facility: Stadtisches Klinikum Karlsruhe gGmbH Medizinischen Klinik I

location_facility: Universitatsmedizin Berlin - Campus Benjamin Franklin (CBF)

location_facility: Vilnius University Hospital Santarisku KLinikos

location_facility: Institut de Cardiologie de Montreal (Montreal Heart Inst.)

location_facility: Azienda Ospedali V. Emanuele Ferrarotto E S. Bambino

location_facility: UKE Hamburg (Universitatsklinik Eppendorf)

intervention_type: Procedure


title: Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of AZD9291 in Patients With Advanced Non Small Cell Lung Cancer Who Progressed on Prior Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent

acronym: AURA

summary: This study will treat patients with advanced NSCLC who have already received at least one course of specific anti-cancer treatment but the tumour has started to re-grow following that treatment. This is the first time this drug has ever been tested in patients, and so it will help to understand what type of side effects may occur with the drug treatment, it will measure the levels of drug in the body, it will also measure the anti-cancer activity. By using these pieces of information together the best dose of this drug to use in further clinical trials will be selected.

ReferenceCitation: Martin ML, Correll J, Walding A, Rydén A. How patients being treated for non-small cell lung cancer value treatment benefit despite side effects. Qual Life Res. 2022 Jan;31(1):135-146. doi: 10.1007/s11136-021-02882-6. Epub 2021 May 31.

ReferenceCitation: Ahn MJ, Han JY, Kim DW, Cho BC, Kang JH, Kim SW, Yang JC, Mitsudomi T, Lee JS. Osimertinib in Patients with T790M-Positive Advanced Non-small Cell Lung Cancer: Korean Subgroup Analysis from Phase II Studies. Cancer Res Treat. 2020 Jan;52(1):284-291. doi: 10.4143/crt.2019.200. Epub 2019 Jul 23.

ReferenceCitation: Ahn MJ, Tsai CM, Shepherd FA, Bazhenova L, Sequist LV, Hida T, Yang JCH, Ramalingam SS, Mitsudomi T, Jänne PA, Mann H, Cantarini M, Goss G. Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: Long-term follow-up from a pooled analysis of 2 phase 2 studies. Cancer. 2019 Mar 15;125(6):892-901. doi: 10.1002/cncr.31891. Epub 2018 Dec 4.

ReferenceCitation: Oxnard GR, Hu Y, Mileham KF, Husain H, Costa DB, Tracy P, Feeney N, Sholl LM, Dahlberg SE, Redig AJ, Kwiatkowski DJ, Rabin MS, Paweletz CP, Thress KS, Jänne PA. Assessment of Resistance Mechanisms and Clinical Implications in Patients With EGFR T790M-Positive Lung Cancer and Acquired Resistance to Osimertinib. JAMA Oncol. 2018 Nov 1;4(11):1527-1534. doi: 10.1001/jamaoncol.2018.2969.

ReferenceCitation: Kiura K, Yoh K, Katakami N, Nogami N, Kasahara K, Takahashi T, Okamoto I, Cantarini M, Hodge R, Uchida H. Osimertinib in patients with epidermal growth factor receptor T790M advanced non-small cell lung cancer selected using cytology samples. Cancer Sci. 2018 Apr;109(4):1177-1184. doi: 10.1111/cas.13511. Epub 2018 Feb 27.

ReferenceCitation: Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crinò L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Jänne PA, Yang JC. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018 Mar 1;29(3):687-693. doi: 10.1093/annonc/mdx820.

ReferenceCitation: Ramalingam SS, Yang JC, Lee CK, Kurata T, Kim DW, John T, Nogami N, Ohe Y, Mann H, Rukazenkov Y, Ghiorghiu S, Stetson D, Markovets A, Barrett JC, Thress KS, Jänne PA. Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 Mar 20;36(9):841-849. doi: 10.1200/JCO.2017.74.7576. Epub 2017 Aug 25.

ReferenceCitation: Thress KS, Jacobs V, Angell HK, Yang JC, Sequist LV, Blackhall F, Su WC, Schuler M, Wolf J, Gold KA, Cantarini M, Barrett JC, Jänne PA. Modulation of Biomarker Expression by Osimertinib: Results of the Paired Tumor Biopsy Cohorts of the AURA Phase I Trial. J Thorac Oncol. 2017 Oct;12(10):1588-1594. doi: 10.1016/j.jtho.2017.07.011. Epub 2017 Jul 24.

ReferenceCitation: Dearden S, Brown H, Jenkins S, Thress KS, Cantarini M, Cole R, Ranson M, Jänne PA. EGFR T790M mutation testing within the osimertinib AURA Phase I study. Lung Cancer. 2017 Jul;109:9-13. doi: 10.1016/j.lungcan.2017.04.011. Epub 2017 Apr 19.

ReferenceCitation: Ballard P, Yates JW, Yang Z, Kim DW, Yang JC, Cantarini M, Pickup K, Jordan A, Hickey M, Grist M, Box M, Johnström P, Varnäs K, Malmquist J, Thress KS, Jänne PA, Cross D. Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity. Clin Cancer Res. 2016 Oct 15;22(20):5130-5140. Epub 2016 Jul 19.

ReferenceCitation: Oxnard GR, Thress KS, Alden RS, Lawrance R, Paweletz CP, Cantarini M, Yang JC, Barrett JC, Jänne PA. Association Between Plasma Genotyping and Outcomes of Treatment With Osimertinib (AZD9291) in Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2016 Oct 1;34(28):3375-82. doi: 10.1200/JCO.2016.66.7162. Epub 2016 Jun 27.

ReferenceCitation: Thress KS, Brant R, Carr TH, Dearden S, Jenkins S, Brown H, Hammett T, Cantarini M, Barrett JC. EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291. Lung Cancer. 2015 Dec;90(3):509-15. doi: 10.1016/j.lungcan.2015.10.004. Epub 2015 Oct 9.

ReferenceCitation: Kim TM, Song A, Kim DW, Kim S, Ahn YO, Keam B, Jeon YK, Lee SH, Chung DH, Heo DS. Mechanisms of Acquired Resistance to AZD9291: A Mutation-Selective, Irreversible EGFR Inhibitor. J Thorac Oncol. 2015 Dec;10(12):1736-44. doi: 10.1097/JTO.0000000000000688.

ReferenceCitation: Yu HA, Tian SK, Drilon AE, Borsu L, Riely GJ, Arcila ME, Ladanyi M. Acquired Resistance of EGFR-Mutant Lung Cancer to a T790M-Specific EGFR Inhibitor: Emergence of a Third Mutation (C797S) in the EGFR Tyrosine Kinase Domain. JAMA Oncol. 2015 Oct;1(7):982-4. doi: 10.1001/jamaoncol.2015.1066.

ReferenceCitation: Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1689-99. doi: 10.1056/NEJMoa1411817.

ipd_sharing: Yes

ipd_sharing_description:
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

lead_sponsor: AstraZeneca

location_country:
Taiwan
Spain
Italy
United Kingdom
Australia
Korea, Republic of
United States
France
Japan
Germany


title: A Three-Part, Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Sequential Adaptive, Phase II Study to Evaluate the Safety, Tolerability and Efficacy of OPN-305, a Humanised Monoclonal Antibody That Blocks Toll-Like Receptor 2, in Renal Transplant Patients at High Risk of Delayed Graft Function

summary:
When a patient receives a kidney transplant particularly if the kidney is from an older donor or one who has had the kidney removed after their heart has stopped, there is a risk that the newly transplanted kidney may not function immediately. If the delay in function means that dialysis is needed in the first 7 days after the transplantation then this is known as delayed graft function or dDGF. Also delayed graft function that does not require dialysis but is present because the serum creatinine does not fall sufficiently is known as functional delayed graft function or fDGF. This problem is often due to an excessive inflammatory reaction to not having had a blood supply between the time of donation and transplant.

OPN-305 is a monoclonal antibody that blocks Toll-like Receptor 2 which is thought to be partly responsible for increasing the risk of this inflammation. It is hoped that the effects of the inflammation will be reduced and therefore prevent dDGF and fDGF from occurring.

The purpose of the study is to explore how effective OPN-305 is in preventing dDGF and fDGF as well as improving other measures of kidney function and the overall safety of the antibody. In the first part of the study, each patient received an Infusion of one of three possible doses of OPN-305 or a placebo and in the second part the most suitable dose of OPN-305 and a placebo would be used. The purpose of this second part of the study is to find out if a dose of OPN-305 which has already been tested in an earlier part of this study can prevent kidney graft dysfunction. For the purposes of this study, kidney function will be assessed using the composite of delayed graft function (dDGF) because dialysis is necessary in the first 7 days and functional delayed graft function that does not require dialysis but is present because the serum creatinine, a key measure of renal function, does not fall sufficiently (fDGF) in the first 7 days post-transplant.

Protocol OPN305-103 follows out to 12 months post-transplant the clinical status and graft function of patients who have completed the 6-month post-transplant period under Part A or Part B of OPN305-102.

primary_purpose: Prevention

lead_sponsor: Opsona Therapeutics Ltd.

location_country:
Poland
Spain
United Kingdom
Austria
Netherlands
Czech Republic
Switzerland
France
United States
Belgium
Germany


title: A Retrospective, Observational, Non-interventional Trial to Assess Eculizumab Treatment Effect in Patients With Atypical Hemolytic Uremic Syndrome (aHUS)

summary: The objective of this retrospective trial is to assess safety and efficacy of eculizumab in aHUS patients treated outside of an Alexion-sponsored controlled clinical trial.

time_perspective: Retrospective

lead_sponsor: Alexion Pharmaceuticals

location_country:
Spain
Austria
Netherlands
Canada
Switzerland
United States
France
Germany


title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Subjects With Heterozygous Familial Hypercholesterolemia

summary: The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneously once every 2 weeks (Q2W) and once monthly (QM), compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with heterozygous familial hypercholesterolemia (HeFH).

ReferenceCitation: Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R, Djedjos C, Wu Y, Geller M, Uhart M, Somaratne R, Wasserman SM; PROFICIO Investigators. Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies. Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1.

ReferenceCitation: Kuchimanchi M, Grover A, Emery MG, Somaratne R, Wasserman SM, Gibbs JP, Doshi S. Population pharmacokinetics and exposure-response modeling and simulation for evolocumab in healthy volunteers and patients with hypercholesterolemia. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):505-522. doi: 10.1007/s10928-018-9592-y. Epub 2018 May 7.

ReferenceCitation: Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7. Review.

ReferenceCitation: Wasserman SM, Sabatine MS, Koren MJ, Giugliano RP, Legg JC, Emery MG, Doshi S, Liu T, Somaratne R, Gibbs JP. Comparison of LDL-C Reduction Using Different Evolocumab Doses and Intervals: Biological Insights and Treatment Implications. J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):423-432. doi: 10.1177/1074248418774043. Epub 2018 May 16.

ReferenceCitation: Raal FJ, Stein EA, Dufour R, Turner T, Civeira F, Burgess L, Langslet G, Scott R, Olsson AG, Sullivan D, Hovingh GK, Cariou B, Gouni-Berthold I, Somaratne R, Bridges I, Scott R, Wasserman SM, Gaudet D; RUTHERFORD-2 Investigators. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Jan 24;385(9965):331-40. doi: 10.1016/S0140-6736(14)61399-4. Epub 2014 Oct 1.

ReferenceCitation: Shapiro MD, Minnier J, Tavori H, Kassahun H, Flower A, Somaratne R, Fazio S. Relationship Between Low-Density Lipoprotein Cholesterol and Lipoprotein(a) Lowering in Response to PCSK9 Inhibition With Evolocumab. J Am Heart Assoc. 2019 Feb 19;8(4):e010932. doi: 10.1161/JAHA.118.010932.

ReferenceCitation: Stroes E, Robinson JG, Raal FJ, Dufour R, Sullivan D, Kassahun H, Ma Y, Wasserman SM, Koren MJ. Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies. Clin Cardiol. 2018 Oct;41(10):1328-1335. doi: 10.1002/clc.23049. Epub 2018 Oct 21.

location_country:
Hong Kong
Spain
United Kingdom
Australia
Netherlands
Canada
New Zealand
Switzerland
Sweden
United States
France
South Africa
Norway
Germany


title: A Double-blind, Randomized, Multicenter Study to Evaluate Safety and Efficacy of AMG 145, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor

summary: The primary objective was to evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab every 2 weeks (Q2W) and monthly (QM), compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic adults unable to tolerate an effective dose of a statin (HMG-CoA (5-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors).

ReferenceCitation: Cho L, Dent R, Stroes ESG, Stein EA, Sullivan D, Ruzza A, Flower A, Somaratne R, Rosenson RS. Persistent Safety and Efficacy of Evolocumab in Patients with Statin Intolerance: a Subset Analysis of the OSLER Open-Label Extension Studies. Cardiovasc Drugs Ther. 2018 Aug;32(4):365-372. doi: 10.1007/s10557-018-6817-7.

ReferenceCitation: Cho L, Rocco M, Colquhoun D, Sullivan D, Rosenson RS, Dent R, Xue A, Scott R, Wasserman SM, Stroes E. Design and rationale of the GAUSS-2 study trial: a double-blind, ezetimibe-controlled phase 3 study of the efficacy and tolerability of evolocumab (AMG 145) in subjects with hypercholesterolemia who are intolerant of statin therapy. Clin Cardiol. 2014 Mar;37(3):131-9. doi: 10.1002/clc.22248. Epub 2014 Jan 29.

ReferenceCitation: Stroes E, Colquhoun D, Sullivan D, Civeira F, Rosenson RS, Watts GF, Bruckert E, Cho L, Dent R, Knusel B, Xue A, Scott R, Wasserman SM, Rocco M; GAUSS-2 Investigators. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol. 2014 Jun 17;63(23):2541-2548. doi: 10.1016/j.jacc.2014.03.019. Epub 2014 Mar 30.

ReferenceCitation: Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, López JAG, Banach M. Effect of Evolocumab on Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a): A Pooled Analysis of Phase 2 and Phase 3 Studies. J Am Heart Assoc. 2020 Mar 3;9(5):e014129. doi: 10.1161/JAHA.119.014129. Epub 2020 Mar 2.

ReferenceCitation: Koren MJ, Jones PH, Robinson JG, Sullivan D, Cho L, Hucko T, Lopez JAG, Fleishman AN, Somaratne R, Stroes E. A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies. Cardiol Ther. 2020 Dec;9(2):447-465. doi: 10.1007/s40119-020-00181-8. Epub 2020 Jun 20.

location_country:
Denmark
Poland
Hong Kong
Spain
United Kingdom
Australia
Netherlands
Canada
Switzerland
United States
France
South Africa
Belgium
Germany


title: Attain Performa(TM) Quadripolar Lead Study

summary: The purpose of the study is to evaluate the safety and efficacy of the Medtronic Attain Performa Quadripolar Leads (Model 4298, 4398, and 4598) during and post the implant procedure. This study will also assess the interactions of the Attain Performa leads with the entire Medtronic CRT-D system.

lead_sponsor: Medtronic Cardiac Rhythm and Heart Failure

location_country:
Serbia
Saudi Arabia
Italy
Spain
United Kingdom
United States
Romania
Belgium
South Africa
Slovenia
Austria
Australia
India
Israel
Norway
Malaysia
Slovakia
Canada
Switzerland
Hungary
Germany
Denmark
Greece
Finland
France
Chile
Netherlands

intervention_type: Device


title: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-CENTER TRIAL OF PREGABALIN AS ADJUNCTIVE THERAPY IN PEDIATRIC AND ADULT SUBJECTS WITH PRIMARY GENERALIZED TONIC-CLONIC SEIZURES - PROTOCOL A0081105

summary: The study is designed to evaluate the safety, tolerability and efficacy of two doses of pregabalin as add-on treatment in pediatric and adult subjects with Primary Generalized Tonic-Clonic (PGTC) seizures as compared to placebo. It is hypothesized that both doses of pregabalin will demonstrated superior efficacy when compared to placebo by reducing PGTC seizure frequency and that pregabalin will be safe and well tolerated.

ReferenceCitation: Driscoll J, Almas M, Gregorian G, Kyrychenko A, Makedonska I, Liu J, Patrick J, Scavone JM, Antinew J; 1105 Study Group. Pregabalin as adjunctive therapy in adult and pediatric patients with generalized tonic-clonic seizures: A randomized, placebo-controlled trial. Epilepsia Open. 2021 Jun;6(2):381-393. doi: 10.1002/epi4.12492. Epub 2021 May 16.

ipd_sharing_description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

lead_sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

location_country:
Croatia
Serbia
Spain
United Kingdom
Ukraine
United States
Romania
Philippines
Montenegro
Poland
Austria
Russian Federation
India
Turkey
Malaysia
Slovakia
Bosnia and Herzegovina
Lebanon
Hungary
China
Bulgaria
Denmark
Belarus
Greece
Korea, Republic of
France

location_facility: Oblasnyi klinichnyi tsentr neirokhirurhii ta nevrolohii,

location_facility: Komunalne nekomertsiine pidpryiemstvo Kharkivskoi oblasnoi rady "Oblasna klinichna psykhiatrychna li

location_facility: Celal Bayar University School of Medicine, Neurology Department

location_facility: Komunalnyi zaklad Lvivskoi oblasnoi rady "Lvivska oblasna klinichna likarnia"

location_facility: Komunalna ustanova "Odeska oblasna psykhiatrychna likarnia 2"

location_facility: Eskisehir Osmangazi University Medical Faculty Department Of Neurology

location_facility: Pediatric Epilepsy Center of Central Florida

location_facility: University General Hospital of Thessaloniki "AHEPA"

location_facility: Military Medical Academy - Multiprofile Hospital for Active Treatment

location_facility: SBHI of Saint Petersburg Psychoneurological Dispensary #5

location_facility: SPHI Leningrad Regional Psychoneurological Dispensary

location_facility: Shanghai Huashan Hospital, Neurology Department

location_facility: Dokuz Eylul Ün. Tip Fakültesi İç Hastalıkları

location_facility: Csongrad Megyei Egeszsegugyi Ellato Kozpont Hodmezovasarhely-Mako

location_facility: Spitalul Clinic de Urgenta "Prof. Dr. Nicolae Oblu"

location_facility: Komunalne nekomertsiine pidpryiemstvo "Odeskyi oblasnyi

location_facility: GBOU VPO "Kazan State Medical University" of Roszdrav

location_facility: Ivano-Frankivska oblasna dytiacha klinichna likarnia

location_facility: Komunalna ustanova "Miska klinichna likarnia #2", nevrolohichne viddilennia

location_facility: Spitalul Clinic de Urgente pentru Copii "Sf. Maria"

location_facility: Multiprofile Hospital for Active Treatment Puls AD

location_facility: LLC City Neurological Center "Sibneiromed"

location_facility: ABMU Local Health Board, Morriston Hospital

location_facility: Scott & White Memorial Hospital and Clinic

location_facility: GBOU VPO Smolensk State Medical University

location_facility: Regional State Budgetary Institution of Ministry of Health

location_facility: Marmara University Pendik Training and Research Hospital

location_facility: Mangala Hospital & Mangala Kidney Foundation

location_facility: Centrul Medical de Diagnostic si Tratament Ambulator Neomed

location_facility: Public Health Institution Hospital Dr Mladen Stojanovic

location_facility: The Barberry National Centre for Mental Health

location_facility: Semmelweis Egyetem, I. Sz. Gyermekgyogyaszati Klinika

location_facility: The First Affiliated Hospital of Chongqing Medical University

location_facility: RSBHI Smolensk Regional Clinical Hospital

location_facility: Neurologicka ambulancia MUDr. Eva Gasparova

location_facility: Derzhavnyi zaklad "Ukrainskyi medychnyi tsentr reabilitatsii ditei z

location_facility: MAHI of the Order of the Red Banner of Labor City Clinical Hospital No. 1

location_facility: CMI Neurologie, Neurofiziologie (EEG, EMG, PEC) Roceanu Adina Maria

location_facility: P D Hinduja National Hospital and Medical Research Centre

location_facility: Komunalnyi zaklad "Dnipropetrovska oblasna dytiacha klinichna likarnia"

location_facility: Instytut Medycyny Wsi im. Witolda Chodzki w Lublinie

location_facility: Barts Health NHS Foundation Trust, The Royal London Hospital

location_facility: Cebu Doctors' University Hospital, Rm Ph 7

location_facility: UZ Vitebsk Regional Childrens Clinical Centre

location_facility: Derzhavna ustanova "Instytut nevrolohii, psykhiatrii ta narkolohii

location_facility: The First Bethune Hospital of Jilin University

location_facility: Perm State Medical University n. a. acad. E.A. Vagner

location_facility: FSBI V.M. Bekhterev National Research Medical Center for

location_facility: St. Luke's Medical Center Cathedral Heights Building

location_facility: NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS

location_facility: Saint George Hospital - University Medical Center

location_facility: Komunalnyi zaklad "Dnipropetrovska dytiacha miska klinichna likarnia No. 5"

location_facility: University Hospital Center Split, Clinic for Neurology

location_facility: Nemocnica s poliklinikou Hlohovec, s.r.o.

location_facility: Institute for Child and Youth Healthcare of Vojvodina

location_facility: State Budgetary Healthcare Institution of Stavropol region

location_facility: Alexian Brothers Center for Psychiatric Research


title: A Phase I, Multi-center, Open-label Study of LEE011 in Patients With Malignant Rhabdoid Tumors and Neuroblastoma

location_country:
United Kingdom
Australia
United States
France
Germany

location_facility: Cincinnati Children's Hospital Medical Center Dept of Oncology

location_facility: St Jude s Childrens Research Hospital Dept of Oncology

location_facility: UCSF Medical Center Dept of Pediatic Oncology

location_facility: Childrens Healthcare of Atlanta Dept of Oncology

summary: LEE011 is a small molecule inhibitor of CDK4/6. LEE011 has demonstrated in vitro and in vivo activity in both tumor models. The primary purpose of this study was to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) in pediatric patients and to delineate a clinical dose to be used in future studies. This study was also to have assessed the safety, tolerability, PK and preliminary evidence of antitumor activity of LEE011 in patients with MRT or neuroblastoma.


title: A Randomized, Double-masked, Placebo-controlled Study of the Safety and Efficacy of Gevokizumab in the Treatment of Subjects With Non-infectious Intermediate, Posterior, or Pan-uveitis Currently Controlled With Systemic Treatment

acronym: EYEGUARD™-C

summary: The purpose of this study is to evaluate the efficacy of gevokizumab in reducing the risk of recurrent uveitic disease in subjects with non-infectious uveitis whose disease is currently controlled with systemic treatment.

lead_sponsor: XOMA (US) LLC

location_country:
Spain
Armenia
Italy
United Kingdom
United States
South Africa
Poland
Portugal
Russian Federation
Australia
Argentina
Tunisia
Israel
Turkey
Mexico
Brazil
Canada
China
Germany
Taiwan
Greece
France


title: An Open Label, Multi-center Imatinib Roll-over Protocol for Patients Who Have Completed a Previous Novartis-sponsored Imatinib Study and Are Judged by the Investigator to Benefit From Continued Imatinib Treatment

ipd_sharing_description:
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

location_country:
Hong Kong
United Kingdom
Finland
Thailand
Switzerland
United States
France
China
Turkey
Romania
Singapore

location_facility: University of Texas MD Anderson Cancer Center UT MD Anderson

location_facility: University of California at Los Angeles UCLA

location_facility: Northwestern University Clinical Research Office

location_facility: Karmanos Cancer Institute Oncology Department

location_facility: Fox Chase Cancer Center Dept.ofFoxChaseCancerCtr.

location_facility: Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Med Dept of Onc

location_facility: Weill Cornell Medical Center Dept. of Oncology

location_facility: Oregon Health and Science University Dept of Oncology

summary: The purpose of this study is to allow continued use of imatinib in patients who are on imatinib treatment in a Novartis-sponsored, Oncology Clinical Development & Medical Affairs (CD&MA) study and are benefiting from the treatment as judged by the investigator.


title: A Long-Term, Open-Label, Safety, Tolerability and Superior Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Patients With Cystinosis

lead_sponsor: Horizon Pharma USA, Inc.

ReferenceCitation: Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009 Mar;20(3):629-37. doi: 10.1681/ASN.2008030287. Epub 2009 Jan 21.

location_country:
United Kingdom
Italy
United States
France
Belgium
Netherlands

location_facility: Radboud University Nijmegen Medical Center

location_facility: California Pacific Medical Center (CPMC) Research Institute

location_facility: Baylor College of Medicine / Texas Childrens Hospital

location_facility: Ann & Robert H. Lurie Children's Hospital of Chicago

summary:
The purpose of this study is to gather information about the effectiveness (how well it works to treat cystinosis) and safety of a new form of cysteamine bitartrate called RP103, compared to the already-approved drug cystinosis patients are taking called Cystagon®.

In cystinosis, the body builds up cystine. When taken regularly, the active ingredient of Cystagon® (cysteamine bitartrate) reduces cystine in the body. RP103 has the same active ingredient as Cystagon® and is designed to reduce cystine in a similar way that Cystagon® does. To decide if RP103 is better than Cystagon®, the study will look at two types of blood tests. One test is pharmacodynamics (PD), which measures the amount of white blood cell (WBC) cystine after taking study drug. WBC cystine is a laboratory test used to find out if cysteamine bitartrate is reducing cystine levels in the body. The second test is pharmacokinetics (PK), which measures the amount of cysteamine in the blood after taking the drug.

RP103 is different from Cystagon®: Instead of the cysteamine bitartrate being absorbed from the stomach, RP103 is designed to be absorbed from the small intestine. This may make the effects of the drug last longer, so that it can be taken twice a day instead of four times a day like Cystagon®.

Some cystinosis patients have bad breath (halitosis) when they take Cystagon®. Study participants who experience bad breath with Cystagon® will be asked if they would like to participate in an optional "halitosis substudy" to investigate this issue by collecting some extra PK blood samples.


type: Registry Identifier

title: A Multinational, Open-Label, Non-Controlled Trial on Safety, Efficacy and Pharmacokinetics of NNC 0129-0000-1003 in Previously Treated Paediatric Patients With Severe Haemophilia A

summary: This trial is conducted globally. The aim of the trial is to investigate safety, efficacy and pharmacokinetics (the exposure of the trial drug in the body) of NNC 0129-0000-1003 (N8-GP) in children with severe haemophilia A who have undergone treatment with previous factor VIII (FVIII) products.

ReferenceCitation: Tosetto A, Neff A, Lentz SR, Santagostino E, Nemes L, Sathar J, Meijer K, Chowdary P, Shen C, Landorph A, Hampton K. Turoctocog alfa pegol provides effective management for major and minor surgical procedures in patients across all age groups with severe haemophilia A: Full data set from the pathfinder 3 and 5 phase III trials. Haemophilia. 2020 May;26(3):450-458. doi: 10.1111/hae.13980. Epub 2020 Apr 15.

ReferenceCitation: Saulyte Trakymiene S, Economou M, Kenet G, Landorph A, Shen C, Kearney S. Long-term safety and efficacy of N8-GP in previously treated pediatric patients with hemophilia A: Final results from pathfinder5. J Thromb Haemost. 2020 Sep;18 Suppl 1(Suppl 1):15-25. doi: 10.1111/jth.15036.

lead_sponsor: Novo Nordisk A/S

location_country:
Brazil
Portugal
United Kingdom
Greece
Italy
Canada
Lithuania
Switzerland
Ukraine
Puerto Rico
United States
France
Israel
Turkey
Japan
Malaysia


title: A Randomized, Double-Blind Study of the Efficacy and Safety of Alirocumab Added on to Atorvastatin Versus Ezetimibe Added on to Atorvastatin Versus Atorvastatin Dose Increase Versus Switch to Rosuvastatin in Patients Who Are Not Controlled on Atorvastatin

summary: This is a randomized, double-blind, active-comparator, parallel-group study in patients at high cardiovascular risk with nonfamilial hypercholesterolemia or heterozygous familial hypercholesterolemia (heFH).

ReferenceCitation: Mahmood T, Minnier J, Ito MK, Li QH, Koren A, Kam IW, Fazio S, Shapiro MD. Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies. Eur J Prev Cardiol. 2021 Jul 23;28(8):816-822. doi: 10.1177/2047487320915803. Epub 2020 Apr 10.

ReferenceCitation: Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.

ReferenceCitation: Ray KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, Eckel RH, Cannon CP. Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation. 2016 Dec 13;134(24):1931-1943. Epub 2016 Oct 24.

ReferenceCitation: Bays H, Gaudet D, Weiss R, Ruiz JL, Watts GF, Gouni-Berthold I, Robinson J, Zhao J, Hanotin C, Donahue S. Alirocumab as Add-On to Atorvastatin Versus Other Lipid Treatment Strategies: ODYSSEY OPTIONS I Randomized Trial. J Clin Endocrinol Metab. 2015 Aug;100(8):3140-8. doi: 10.1210/jc.2015-1520. Epub 2015 Jun 1.

ReferenceCitation: Robinson JG, Colhoun HM, Bays HE, Jones PH, Du Y, Hanotin C, Donahue S. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies. Clin Cardiol. 2014 Oct;37(10):597-604. doi: 10.1002/clc.22327. Epub 2014 Sep 30.

lead_sponsor: Regeneron Pharmaceuticals

location_country:
Spain
Italy
United Kingdom
Australia
Canada
United States
France
Mexico
Germany


title: A Phase 3 Evaluation of Daclatasvir in Combination With Peginterferon Lambda-1a and Ribavirin (RBV) or Telaprevir in Combination With Peginterferon Alfa-2a and RBV in Patients With Chronic Hepatitis C Genotype 1b Who Are Treatment naïve or Prior Relapsers to Alfa/RBV Therapy (the STRUCTURE Study)

acronym: STRUCTURE

summary: The purpose of this study is to determine if treatment with Pegylated Interferon Lambda-1a, given in combination with Ribavirin and Daclatasvir for 24 weeks, is as safe and effective as the standard treatment with Pegylated Interferon Alfa-2a + Ribavirin + Telaprevir in subjects who are infected with Chronic Hepatitis C virus genotype 1b and have never received any prior anti-HCV treatment, or who have relapsed after an initial, successful treatment with Pegylated Interferon Alfa + Ribavirin

ReferenceCitation: Flisiak R, Kawazoe S, Znoyko O, Assy N, Gadano A, Kao JH, Lee KS, Zwirtes R, Portsmouth S, Dong Y, Xu D, Kumada H, Srinivasan S. Peginterferon Lambda-1a/Ribavirin with Daclatasvir or Peginterferon Alfa-2a/Ribavirin with Telaprevir for Chronic Hepatitis C Genotype 1b. J Interferon Cytokine Res. 2016 Nov;36(11):635-643. Epub 2016 Jun 21.

lead_sponsor: Bristol-Myers Squibb

location_country:
Poland
Taiwan
Spain
Italy
Russian Federation
United Kingdom
Argentina
Korea, Republic of
Israel
United States
France
Japan
Germany

location_facility: Gastrointestinal Specialists Of Georgia Pc

location_facility: Premier Medical Group Of The Hudson Valley, Pc


title: A Randomized, Open-Label, Multicenter Phase II Study of Ipilimumab Retreatment Versus Chemotherapy for Subjects With Advanced Melanoma Who Progressed After Initially Achieving Disease Control With Ipilimumab Therapy

summary: The purpose of the study is to determine whether additional doses of ipilimumab have a positive effect on survival in the treatment of advanced melanoma that has progressed after successful initial treatment with ipilimumab.

location_country:
Italy
Austria
United States
France
Germany

location_facility: Birmingham Hematology & Oncology Associates Llc

location_facility: Investigative Clinical Research Of Indiana, Llc


title: An Open-label Phase II Study of BKM120 in Subjects With Relapsed and Refractory Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma and Follicular Lymphoma

summary: This is a phase II study evaluating the safety, tolerability and efficacy of BKM120 in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) or follicular lymphoma (FL).

ReferenceCitation: Younes A, Salles G, Martinelli G, Bociek RG, Barrigon DC, Barca EG, Turgut M, Gerecitano J, Kong O, Pisal CB, Tavorath R, Kim WS. Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma. Haematologica. 2017 Dec;102(12):2104-2112. doi: 10.3324/haematol.2017.169656. Epub 2017 Sep 29.

location_country:
Spain
Italy
Korea, Republic of
United States
France
Turkey
Belgium
Germany

location_facility: University of Nebraska Medical Center Univ Nebraska

location_facility: University of Texas MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(3)

location_facility: Medical University of South Carolina -Hollings Cancer Center Medical Univ of South Carolina


title: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 18-Month Safety and Efficacy Study of TRx0237 in Subjects With Mild Alzheimer's Disease

summary: The purpose of this study is to determine the safety and efficacy of TRx0237 in the treatment of subjects with mild Alzheimer's Disease.

lead_sponsor: TauRx Therapeutics Ltd

location_country:
Croatia
Spain
Italy
United Kingdom
Australia
Netherlands
Canada
Finland
United States
France
Belgium
Germany

location_facility: Neurological Associates of Albany, P. C.

location_facility: Memory Enhancement Centers of America, Inc

location_facility: Kingshill Research Centre, Victoria Hospital

location_facility: Sussex Partnership NHS Foundation Trust, Cognitive Treatment and Research Unit

location_facility: Alzheimer's Research and Treatment Center

location_facility: Premiere Research Institute (Palm Beach Neurology)

location_facility: Azienda Ospedaliera Universitaria Sant'Andrea di Roma - Unita' di Neurologia

location_facility: Fondazione Universita 'G. D'Annunzio di Chieti

location_facility: Research Center for Clinical Studies, Inc

location_facility: Ruan Neurology Clinic and Research Center

location_facility: University Hospital Centre Zagreb, Department of Neurology

location_facility: University of Eastern Finland, Brain Research Unit Mediteknia

location_facility: IRCCS San Giovanni di Dio - Fatebenefratelli

location_facility: Research Foundation for Mental Hygiene, Inc.

location_facility: Institute for Neurodegenerative Disorders

location_facility: Advanced Memory Research Institute of NJ PC

location_facility: Alzheimer Center Southwest Netherlands, Erasmus MC

location_facility: University Medicine Berlin - Charité, CBF, Neurology

location_facility: Klinik und Poliklinik für Psychiatrie und Psychotherapie Zentrum für Nervenheilkunde - Universitätsklinikum Rostock

location_facility: Clinical Neurology Department of Neuroscience (DINOGMI) - University of Genoa

location_facility: Neurozentrum Achim Dr. med. Andreas Mahler

location_facility: A.O.U. Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi

location_facility: Memory Assessment and Research Centre (MARC)

location_facility: University Hospital Gent Department of Neurology

location_facility: Xenoscience, Inc / 21st Century Neurology

location_facility: University Hospital Brussels Department of Neurology

location_facility: Discipline of Psychiatry, University of Queensland

location_facility: Neurological Research Center - Hattiesburg Clinic

location_facility: University of British Columbia Hospital, Clinic for Alzheimer Disease and Related Disorders

location_facility: Alexian Brothers Neurosciences Institute

location_facility: Clinical Neuroscience Solutions CNS Healthcare


title: THERMOCOOL® SMARTTOUCH™ Catheter for the Treatment of Symptomatic Atrial Fibrillation- Registry

summary: The primary purpose of this registry is to obtain "real world" clinical use of contact force measurements during ablation procedures.

ReferenceCitation: De Potter T, Van Herendael H, Balasubramaniam R, Wright M, Agarwal SC, Sanders P, Khaykin Y, Latcu DG, Maury P, Pani A, Hayes J, Kalman J, Nery P, Duncan E. Safety and long-term effectiveness of paroxysmal atrial fibrillation ablation with a contact force-sensing catheter: real-world experience from a prospective, multicentre observational cohort registry. Europace. 2018 Nov 1;20(FI_3):f410-f418. doi: 10.1093/europace/eux290.

lead_sponsor: Biosense Webster, Inc.

location_country:
United Kingdom
Italy
Australia
Canada
Monaco
France
Belgium
Germany

location_facility: Melbourne Health/Royal Melbourne Hospital

location_facility: University of Adelaide/Royal Adelaide Hospital

location_facility: OLV Hospital Aalst Cardiovascular Center


title: Observational Study of Optical Coherence Tomography (OCT) in Patients Undergoing Fractional Flow Reserve (FFR) and Percutaneous Coronary Intervention Stage I (ILUMIEN I)

acronym: ILUMIEN I

summary: The purpose of this study is to define and evaluate optical coherence tomography (OCT) stent guidance parameters through prospective data collection in percutaneous coronary intervention (PCI) procedures of de novo lesions.

ReferenceCitation: Wijns W, Shite J, Jones MR, Lee SW, Price MJ, Fabbiocchi F, Barbato E, Akasaka T, Bezerra H, Holmes D. Optical coherence tomography imaging during percutaneous coronary intervention impacts physician decision-making: ILUMIEN I study. Eur Heart J. 2015 Dec 14;36(47):3346-55. doi: 10.1093/eurheartj/ehv367. Epub 2015 Aug 4.

location_country:
Spain
Italy
Austria
Australia
Netherlands
Canada
United Kingdom
United States
France
China
Belgium
Japan
Germany
Czechia

location_facility: University Hospital - Univ. of Alabama at Birmingham (UAB)

location_facility: University of Texas Medical Branch at Galveston

location_facility: Kobe University Graduate School of Medicine


title: A Phase III Open-label, Multicenter, Pharmacokinetic, Safety and Efficacy Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Previously Treated Children With Hemophilia B

summary: This study will examine the pharmacokinetics, safety and efficacy of rIX-FP for the control and prevention of bleeding episodes in children who have previously received factor replacement therapy for hemophilia B.

ReferenceCitation: Kenet G, Chambost H, Male C, Lambert T, Halimeh S, Chernova T, Mancuso ME, Curtin J, Voigt C, Li Y, Jacobs I, Santagostino E; PROLONG-9FP Investigator Study Group. Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children. Results of a phase 3 trial. Thromb Haemost. 2016 Sep 27;116(4):659-68. doi: 10.1160/TH16-03-0179. Epub 2016 Sep 1.

lead_sponsor: CSL Behring

location_country:
Spain
Italy
Austria
Australia
Russian Federation
Canada
Czech Republic
France
Israel
Germany

location_facility: IRCCS Ospendale Maggiore (Centro emofilia e Trombosi)

location_facility: The Royal Children's Hospital, Melbourne

location_facility: FGU "Kirov Research Institute of Haemotology and Blood Trans)

location_facility: C.R.T.H. Hopital de Bicentre (Hemophilie)


title: A Phase II Multicenter, Parallel-Group, Randomized, Dose-Ranging Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Following 12 Weeks of Oral Administration of GSK2336805 With Pegylated Interferon and Ribavirin in Treatment-Naïve Subjects With Chronic Genotype 1 or 4 Hepatitis C Infection

summary:
GSK2336805 is a novel hepatitis C virus (HCV) non-structural 5A (NS5A) inhibitor being developed for the treatment of chronic HCV infection. This Phase II, multicenter, parallel-group, randomized, dose-ranging study will assess the safety and tolerability, antiviral activity, and pharmacokinetics of GSK2336805 at 2 dose levels (40 and 60 mg) in combination with pegylated interferon alfa-2a (PEG) and ribavirin (RIBA) in approximately 100 treatment-naïve subjects with chronic genotype 1 HCV infection.

In a separate nonrandomized single-arm cohort, up to 15 treatment-naïve subjects with genotype 4 chronic HCV infection will be enrolled in parallel at the dose level of 60 mg of GSK2336805.

ReferenceCitation: Protocol contains no citations

ipd_sharing_description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

lead_sponsor: GlaxoSmithKline

location_country:
Puerto Rico
United States
France
Belgium
Germany
Bulgaria


title: A Multi-center, Intra-patient Dose Escalation Phase II Study to Evaluate the Preliminary Efficacy, Safety and Pharmacokinetics of Pasireotide (SOM230) Subcutaneous (s.c.) Followed by Pasireotide LAR in Patients With Dumping Syndrome

summary: multi-center, phase II study evaluating efficacy, safety and pharmacokinetics of pasireotide in patients with dumping syndrome

lead_sponsor: Novartis Pharmaceuticals

location_country:
Netherlands
United States
France
Belgium
Germany

location_facility: Stanford University Medical Center SC - SOM230X2203

location_facility: Ximed Center for Weight Management Ximed Research

location_facility: Texas Tech University Health Science Center


title: A Randomized, Double-blind, Placebo Controlled, Multicenter Study of Subcutaneous Secukinumab in Autoinjectors to Demonstrate Efficacy After Twelve Weeks of Treatment, and to Assess the Safety, Tolerability, Usability and Long-term Efficacy in Subjects With Chronic Plaque-type Psoriasis

acronym: JUNCTURE

summary: The purpose of this study was to demonstrate efficacy of autoinjector administered secukinumab at Week 12 based on PASI and IGA response rates versus placebo in subjects with moderate to severe chronic plaque-type psoriasis.

ReferenceCitation: Merola JF, McInnes IB, Deodhar AA, Dey AK, Adamstein NH, Quebe-Fehling E, Aassi M, Peine M, Mehta NN. Effect of Secukinumab on Traditional Cardiovascular Risk Factors and Inflammatory Biomarkers: Post Hoc Analyses of Pooled Data Across Three Indications. Rheumatol Ther. 2022 Jun;9(3):935-955. doi: 10.1007/s40744-022-00434-z. Epub 2022 Mar 19.

ReferenceCitation: Houghton K, Patil D, Gomez B, Feldman SR. Correlation Between Change in Psoriasis Area and Severity Index and Dermatology Life Quality Index in Patients with Psoriasis: Pooled Analysis from Four Phase 3 Clinical Trials of Secukinumab. Dermatol Ther (Heidelb). 2021 Aug;11(4):1373-1384. doi: 10.1007/s13555-021-00564-2. Epub 2021 Jun 10.

ReferenceCitation: Menter A, Cather JC, Jarratt M, Meng X, Guana A, Nyirady J. Efficacy of Secukinumab on Moderate-to-severe Plaque Psoriasis Affecting Different Body Regions: a Pooled Analysis of Four Phase 3 Studies. Dermatol Ther (Heidelb). 2016 Dec;6(4):639-647. Epub 2016 Aug 30.

ReferenceCitation: Kircik L, Fowler J, Weiss J, Meng X, Guana A, Nyirady J. Efficacy of Secukinumab for Moderate-to-Severe Head and Neck Psoriasis Over 52 Weeks: Pooled Analysis of Four Phase 3 Studies. Dermatol Ther (Heidelb). 2016 Dec;6(4):627-638. Epub 2016 Aug 30.

ReferenceCitation: Paul C, Lacour JP, Tedremets L, Kreutzer K, Jazayeri S, Adams S, Guindon C, You R, Papavassilis C; JUNCTURE study group. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol. 2015 Jun;29(6):1082-90. doi: 10.1111/jdv.12751. Epub 2014 Sep 22.

location_country:
Estonia
Canada
United States
France
Germany


title: Prospective, International, Multi-Center, Randomized Clinical Investigation of TransMedics Organ Care System (OCS LUNG) for Lung Preservation and Transplantation

acronym: INSPIRE

summary: A prospective, international, multi-center, randomized controlled trial comparing preservation of donor lungs using OCS-Lung perfusion device (Treatment Group) to cold flush and storage (Control Group).

ReferenceCitation: Warnecke G, Van Raemdonck D, Smith MA, Massard G, Kukreja J, Rea F, Loor G, De Robertis F, Nagendran J, Dhital KK, Moradiellos Díez FJ, Knosalla C, Bermudez CA, Tsui S, McCurry K, Wang IW, Deuse T, Lesèche G, Thomas P, Tudorache I, Kühn C, Avsar M, Wiegmann B, Sommer W, Neyrinck A, Schiavon M, Calabrese F, Santelmo N, Olland A, Falcoz PE, Simon AR, Varela A, Madsen JC, Hertz M, Haverich A, Ardehali A. Normothermic ex-vivo preservation with the portable Organ Care System Lung device for bilateral lung transplantation (INSPIRE): a randomised, open-label, non-inferiority, phase 3 study. Lancet Respir Med. 2018 May;6(5):357-367. doi: 10.1016/S2213-2600(18)30136-X. Epub 2018 Apr 9. Erratum in: Lancet Respir Med. 2018 Jun;6(6):e27.

ReferenceCitation: Bozso S, Freed D, Nagendran J. Successful transplantation of extended criteria lungs after prolonged ex vivo lung perfusion performed on a portable device. Transpl Int. 2015 Feb;28(2):248-50. doi: 10.1111/tri.12474. Epub 2014 Oct 27.

lead_sponsor: TransMedics

location_country:
Spain
Italy
United Kingdom
Australia
Canada
United States
France
Belgium
Germany

location_facility: University of California at San Francisco

location_facility: Groupe Hospitalier Hopitaux Universitaries

location_facility: St. Joseph's Hospital and Medical Center


title: A Phase III, Multicentre, Randomized, Double-blind Clinical Study, Investigating the Efficacy and Safety of Repeated 12-week Courses of Daily 5mg or 10mg Doses of PGL4001 for the Long-term Management of Symptomatic Uterine Fibroids

acronym: PEARLIV

summary: Phase III, multicentre, randomized, double-blind, parallel group, long-term study investigating the efficacy and safety of the 5mg and 10mg doses of PGL4001 for the treatment of uterine myoma.

ReferenceCitation: Donnez J, Donnez O, Matule D, Ahrendt HJ, Hudecek R, Zatik J, Kasilovskiene Z, Dumitrascu MC, Fernandez H, Barlow DH, Bouchard P, Fauser BC, Bestel E, Loumaye E. Long-term medical management of uterine fibroids with ulipristal acetate. Fertil Steril. 2016 Jan;105(1):165-173.e4. doi: 10.1016/j.fertnstert.2015.09.032. Epub 2015 Oct 23.

ReferenceCitation: Donnez J, Hudecek R, Donnez O, Matule D, Arhendt HJ, Zatik J, Kasilovskiene Z, Dumitrascu MC, Fernandez H, Barlow DH, Bouchard P, Fauser BC, Bestel E, Terrill P, Osterloh I, Loumaye E. Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids. Fertil Steril. 2015 Feb;103(2):519-27.e3. doi: 10.1016/j.fertnstert.2014.10.038. Epub 2014 Dec 24.

lead_sponsor: PregLem SA

location_country:
Romania
United Kingdom
Italy
Latvia
Lithuania
Ukraine
Hungary
France
Belgium
Germany
Czechia

location_facility: Rethy Pal Korhaz és Rendelointezet Szuleszeti es Nogyogyaszati Osztaly

location_facility: CHU Bretonneau Service de Gynécologie Obstétrique

location_facility: Quantum Medical Center SRL Obstetrica-Ginecologie

location_facility: Szent Anna Szuleszeti, Nogyogyaszati es Ultrahang Maganrendelo

location_facility: North Middlesex University Hospital NHS Trust

location_facility: Cliniques Universitaires Saint-Luc Gynécologie-Obstétrique

location_facility: Maternity Hospital#4 Department of Gynaecology

location_facility: Nemocnice Jihlava Gynekologicko - porodnicke oddeleni

location_facility: Medizinische Hochschule Hannover Klinik für Frauenheilkunde und Geburtshilfe

location_facility: Family Medicine Centre"Seimos Gydytojas"

location_facility: Praxis für Frauenheilkunde, Klinische Forschung und Weiterbildung

location_facility: Fortis Medical Center SRL Obstetrica Ginecologie

location_facility: Women's Health, Royal Victoria Infirmary

location_facility: Dipartimento di Ostetricia e Ginecologia, Università degli Studi di Catanzaro "Magna Graecia"

location_facility: Hôpital Bichat, Service de Gynécologie Obstétrique

location_facility: Municipal Institution "Maternity Hospital #1" City Center of family planning

location_facility: Policlinico Universitario "Agostino Gemelli"

location_facility: FN Olomouc, Porodnicko-Gynekologicka klinika

location_facility: MRC Centre for Reproductive Health University of Edinburgh

location_facility: Spitalul Clinic Dr. I.Cantacuzino sectia Obstetrica-Ginecologie

location_facility: Centrul Medical EUROMED SRL, Departamentul de Obtetrica/Ginecologie

location_facility: Centrum ambulantni gynekologie a primarni pece

location_facility: Kharkiv City Perinatal Center Gynaecological Department #1

location_facility: CHU de Liège, CHR de la Citadelle Gynécologie-Obstétrique

location_facility: Fejer Megyei Szent Gyorgy Korhaz Szuleszeti es Nogyogyaszati Osztaly

location_facility: FN Brno Gynekologicko - porodnická klinika


title: A Phase I/II Study of AZD5363 Combined With Paclitaxel in Patients With Advanced or Metastatic Breast Cancer. Comprising a Safety Run-In and a Placebo-controlled Randomised Expansion in ER+ve Patients Stratified by PIK3CA Mutation Status

acronym: BEECH

summary: The purpose of this study is to investigate the safety and efficacy of different doses and schedules of AZD5363, when in combination with paclitaxel, in treatment of patients with advanced or metastatic breast cancer. Also to investigate a selected dose and schedule of AZD5363 in combination with paclitaxel vs. paclitaxel in combination with placebo in treatment of patients with estrogen receptor-positive advanced or metastatic breast cancer, including a subgroup who have the phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) tumour mutation.

ReferenceCitation: Hrebien S, Citi V, Garcia-Murillas I, Cutts R, Fenwick K, Kozarewa I, McEwen R, Ratnayake J, Maudsley R, Carr TH, de Bruin EC, Schiavon G, Oliveira M, Turner N. Early ctDNA dynamics as a surrogate for progression-free survival in advanced breast cancer in the BEECH trial. Ann Oncol. 2019 Jun 1;30(6):945-952. doi: 10.1093/annonc/mdz085.

ReferenceCitation: Turner NC, Alarcón E, Armstrong AC, Philco M, López Chuken YA, Sablin MP, Tamura K, Gómez Villanueva A, Pérez-Fidalgo JA, Cheung SYA, Corcoran C, Cullberg M, Davies BR, de Bruin EC, Foxley A, Lindemann JPO, Maudsley R, Moschetta M, Outhwaite E, Pass M, Rugman P, Schiavon G, Oliveira M. BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population. Ann Oncol. 2019 May 1;30(5):774-780. doi: 10.1093/annonc/mdz086.

ipd_sharing_description:
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

lead_sponsor: AstraZeneca

location_country:
Spain
United Kingdom
Canada
Korea, Republic of
France
Peru
Mexico
Japan
Singapore
Bulgaria
Czechia


title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of SAR236553/REGN727 in Patients With Heterozygous Familial Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy

acronym: ODYSSEY FH I

summary:
Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).

Primary Objective of the study:

To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 24 weeks of treatment in comparison with placebo.

Secondary Objectives:

To evaluate the effect of alirocumab in comparison with placebo on LDL-C at other time points
To evaluate the effects of alirocumab on other lipid parameters
To evaluate the safety and tolerability of alirocumab

ReferenceCitation: Kastelein JJ, Robinson JG, Farnier M, Krempf M, Langslet G, Lorenzato C, Gipe DA, Baccara-Dinet MT. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy: design and rationale of the ODYSSEY FH studies. Cardiovasc Drugs Ther. 2014 Jun;28(3):281-9. doi: 10.1007/s10557-014-6523-z.

ReferenceCitation: Kastelein JJ, Ginsberg HN, Langslet G, Hovingh GK, Ceska R, Dufour R, Blom D, Civeira F, Krempf M, Lorenzato C, Zhao J, Pordy R, Baccara-Dinet MT, Gipe DA, Geiger MJ, Farnier M. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015 Nov 14;36(43):2996-3003. doi: 10.1093/eurheartj/ehv370. Epub 2015 Sep 1.

ReferenceCitation: Mahmood T, Minnier J, Ito MK, Li QH, Koren A, Kam IW, Fazio S, Shapiro MD. Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies. Eur J Prev Cardiol. 2021 Jul 23;28(8):816-822. doi: 10.1177/2047487320915803. Epub 2020 Apr 10.

ReferenceCitation: Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.

ReferenceCitation: Defesche JC, Stefanutti C, Langslet G, Hopkins PN, Seiz W, Baccara-Dinet MT, Hamon SC, Banerjee P, Kastelein JJP. Efficacy of alirocumab in 1191 patients with a wide spectrum of mutations in genes causative for familial hypercholesterolemia. J Clin Lipidol. 2017 Nov - Dec;11(6):1338-1346.e7. doi: 10.1016/j.jacl.2017.08.016. Epub 2017 Sep 4. Erratum in: J Clin Lipidol. 2020 Sep - Oct;14(5):742.

ReferenceCitation: Kastelein JJ, Hovingh GK, Langslet G, Baccara-Dinet MT, Gipe DA, Chaudhari U, Zhao J, Minini P, Farnier M. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody alirocumab vs placebo in patients with heterozygous familial hypercholesterolemia. J Clin Lipidol. 2017 Jan - Feb;11(1):195-203.e4. doi: 10.1016/j.jacl.2016.12.004. Epub 2016 Dec 28.

ReferenceCitation: Ray KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, Eckel RH, Cannon CP. Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation. 2016 Dec 13;134(24):1931-1943. Epub 2016 Oct 24.

lead_sponsor: Sanofi

location_country:
Denmark
Spain
United Kingdom
Austria
Russian Federation
Canada
Czech Republic
Sweden
United States
France
Israel
South Africa
Norway
Netherlands

location_facility:
Investigational Site Number 840409
Investigational Site Number 840401
Investigational Site Number 840418
Investigational Site Number 528406
Investigational Site Number 643410
Investigational Site Number 528409
Investigational Site Number 250403
Investigational Site Number 840407
Investigational Site Number 040403
Investigational Site Number 724407
Investigational Site Number 710402
Investigational Site Number 840410
Investigational Site Number 840452
Investigational Site Number 840455
Investigational Site Number 724401
Investigational Site Number 203405
Investigational Site Number 528412
Investigational Site Number 840428
Investigational Site Number 840425
Investigational Site Number 578401
Investigational Site Number 710405
Investigational Site Number 643401
Investigational Site Number 376405
Investigational Site Number 724404
Investigational Site Number 040405
Investigational Site Number 840415
Investigational Site Number 643408
Investigational Site Number 840417
Investigational Site Number 203402
Investigational Site Number 840461
Investigational Site Number 643407
Investigational Site Number 724405
Investigational Site Number 710409
Investigational Site Number 724408
Investigational Site Number 724409
Investigational Site Number 724403
Investigational Site Number 528411
Investigational Site Number 040402
Investigational Site Number 840430
Investigational Site Number 840422
Investigational Site Number 250402
Investigational Site Number 643406
Investigational Site Number 203401
Investigational Site Number 643413
Investigational Site Number 840421
Investigational Site Number 643404
Investigational Site Number 840424
Investigational Site Number 840456
Investigational Site Number 826403
Investigational Site Number 840412
Investigational Site Number 124407
Investigational Site Number 528410
Investigational Site Number 203403
Investigational Site Number 528416
Investigational Site Number 840408
Investigational Site Number 643402
Investigational Site Number 840419
Investigational Site Number 826408
Investigational Site Number 124406
Investigational Site Number 643412
Investigational Site Number 124401
Investigational Site Number 840404
Investigational Site Number 643409
Investigational Site Number 752404
Investigational Site Number 250401
Investigational Site Number 528408
Investigational Site Number 376404
Investigational Site Number 840411
Investigational Site Number 376401
Investigational Site Number 840429
Investigational Site Number 710404
Investigational Site Number 208401
Investigational Site Number 840426
Investigational Site Number 826402
Investigational Site Number 826409
Investigational Site Number 710406
Investigational Site Number 724406
Investigational Site Number 826405
Investigational Site Number 840406
Investigational Site Number 752401
Investigational Site Number 710407
Investigational Site Number 710403
Investigational Site Number 208403
Investigational Site Number 124404
Investigational Site Number 376402
Investigational Site Number 724402
Investigational Site Number 710401
Investigational Site Number 710408
Investigational Site Number 124403
Investigational Site Number 840460
Investigational Site Number 528402


title: A Phase 3, Two-Part, Randomized, Double-Blind, Placebo-Controlled, Crossover Study With an Open-Label Period to Evaluate the Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Who Have a Non-G551D CFTR Gating Mutation

acronym: KONNECTION

summary: The purpose of this study is to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis (CF) who have a non-G551D cystic fibrosis transmembrane regulator (CFTR) gating mutation (any one of the following CFTR mutations: G178R, G551S, S549N, S549R, G970R, G1244E, S1251N, S1255P, or G1349D).

lead_sponsor: Vertex Pharmaceuticals Incorporated

location_country:
United States
France
Belgium


title: Prospective, Open-label, Non-randomized, Single-arm, Multi-center Dose Titration Study to Investigate the Safety and Efficacy of NT 201 in Subjects Deemed to Require Total Body Doses of 800 U of NT 201 During the Course of the Study for the Treatment of Upper and Lower Limb Spasticity of the Same Body Side Due to Cerebral Causes

summary: The purpose of this study is to determine whether injections with increasing doses (up to 800 units) of Botulinum toxin type A into muscles of the leg and/or arm are safe and effective in treating patients with spasticity on one body side due to cerebral causes.

ReferenceCitation: Wissel J, Bensmail D, Ferreira JJ, Molteni F, Satkunam L, Moraleda S, Rekand T, McGuire J, Scheschonka A, Flatau-Baqué B, Simon O, Rochford ET, Dressler D, Simpson DM; TOWER study investigators. Safety and efficacy of incobotulinumtoxinA doses up to 800 U in limb spasticity: The TOWER study. Neurology. 2017 Apr 4;88(14):1321-1328. doi: 10.1212/WNL.0000000000003789. Epub 2017 Mar 10.

ReferenceCitation: Fheodoroff K, Scheschonka A, Wissel J. Goal analysis in patients with limb spasticity treated with incobotulinumtoxinA in the TOWER study. Disabil Rehabil. 2022 Apr;44(8):1367-1373. doi: 10.1080/09638288.2020.1804627. Epub 2020 Aug 17.

ReferenceCitation: Fheodoroff K, Rekand T, Medeiros L, Koßmehl P, Wissel J, Bensmail D, Scheschonka A, Flatau-Baqué B, Simon O, Dressler D, Simpson DM. Quality of life in subjects with upper- and lower-limb spasticity treated with incobotulinumtoxinA. Health Qual Life Outcomes. 2020 Mar 4;18(1):51. doi: 10.1186/s12955-020-01304-4.

lead_sponsor: Merz Pharmaceuticals GmbH

location_country:
Portugal
Spain
Italy
Canada
United States
France
Norway
Germany

location_facility:
Merz Investigational Site # 001232
Merz Investigational Site #049022
Merz Investigational Site #049298
Merz Investigational Site # 033050
Merz Investigational Site # 039015
Merz Investigational Site # 001203
Merz Investigational Site #001238
Merz Investigational Site #049191
Merz Investigational Site #001237
Merz Investigational Site #034007
Merz Investigational Site # 351001
Merz Investigational Site #039016
Merz Investigational Site # 001197
Merz Investigational Site #049300
Merz Investigational Site #034025
Merz Investigational Site # 039017
Merz Investigational Site # 039010
Merz Investigational Site # 001235
Merz Investigational Site #047001
Merz Investigational Site #033049
Merz Investigational Site #039013
Merz Investigational site #001195
Merz Investigational Site #034024
Merz Investigational Site # 351003
Merz Investigational Site # 039005
Merz Investigational Site #049295
Merz Investigational Site #034022
Merz Investigational Site #039014
Merz Investigational Site #049296
Merz Investigational Site # 033018
Merz Investigational Site #049297
Merz Investigational Site # 049153
Merz Investigational Site # 001191


title: A Phase I/II Open-Label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GSK525762 in Subjects With NUT Midline Carcinoma (NMC) and Other Cancers

ReferenceCitation: Piha-Paul SA, Hann CL, French CA, Cousin S, Braña I, Cassier PA, Moreno V, de Bono JS, Harward SD, Ferron-Brady G, Barbash O, Wyce A, Wu Y, Horner T, Annan M, Parr NJ, Prinjha RK, Carpenter CL, Hilton J, Hong DS, Haas NB, Markowski MC, Dhar A, O'Dwyer PJ, Shapiro GI. Phase 1 Study of Molibresib (GSK525762), a Bromodomain and Extra-Terminal Domain Protein Inhibitor, in NUT Carcinoma and Other Solid Tumors. JNCI Cancer Spectr. 2019 Nov 6;4(2):pkz093. doi: 10.1093/jncics/pkz093. eCollection 2020 Apr.

ReferenceCitation: Cousin S, Blay JY, Garcia IB, de Bono JS, Le Tourneau C, Moreno V, Trigo J, Hann CL, Azad AA, Im SA, Cassier PA, French CA, Italiano A, Keedy VL, Plummer R, Sablin MP, Hemming ML, Ferron-Brady G, Wyce A, Khaled A, Datta A, Foley SW, McCabe MT, Wu Y, Horner T, Kremer BE, Dhar A, O'Dwyer PJ, Shapiro GI, Piha-Paul SA. Safety, pharmacokinetic, pharmacodynamic and clinical activity of molibresib for the treatment of nuclear protein in testis carcinoma and other cancers: Results of a Phase I/II open-label, dose escalation study. Int J Cancer. 2022 Mar 15;150(6):993-1006. doi: 10.1002/ijc.33861. Epub 2021 Nov 26.

ReferenceCitation: Krishnatry AS, Voelkner A, Dhar A, Prohn M, Ferron-Brady G. Population pharmacokinetic modeling of molibresib and its active metabolites in patients with solid tumors: A semimechanistic autoinduction model. CPT Pharmacometrics Syst Pharmacol. 2021 Jul;10(7):709-722. doi: 10.1002/psp4.12639. Epub 2021 Jun 4.

ReferenceCitation: Parikh SA, French CA, Costello BA, Marks RS, Dronca RS, Nerby CL, Roden AC, Peddareddigari VG, Hilton J, Shapiro GI, Molina JR. NUT midline carcinoma: an aggressive intrathoracic neoplasm. J Thorac Oncol. 2013 Oct;8(10):1335-8. doi: 10.1097/JTO.0b013e3182a00f41.

location_country:
Spain
United Kingdom
Australia
Korea, Republic of
United States
France
Netherlands

summary: This study is divided into two parts; Part 1 of the study is a dose escalation phase to select the recommended dose for Part 2 based on the safety, pharmacokinetic, and pharmacodynamic profiles observed after oral administration of GSK525762 in the following subjects: NMC, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), neuroblastoma (NB), castration resistant prostate cancer (CRPC), triple negative breast cancer (TNBC), estrogen receptor positive (ER positive) breast cancer, and MYCN driven solid tumor subjects. Part 2 of the study will explore the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of the recommended dose from Part 1 in cohorts comprised of NMC, small cell lung cancer (SCLC), castration resistant prostate cancer (CRPC), triple negative breast cancer (TNBC), and estrogen receptor positive (ER positive) breast cancer subjects. Approximately 60 subjects will be enrolled in the Part 1 and approximately 150 subjects will be enrolled in Part 2. A sub-study will be opened in Part 1 to approximately 10-12 subjects in the United States to investigate the relative bioavailability of the besylate tablet compared to the amorphous free-base tablet at the maximum tolerated dose (MTD) or recommended phase 2 dosing (RP2D), the effect of high-fat high-calorie meal on the bioavailability of the besylate tablet at the MTD or RP2D and the dose proportionality of 2 doses of GSK525762 administered as besylate tablet.


title: International, Multicenter, Open-label, Treatment-extension Study for Subjects Who Completed a Phase 1 or Phase 2 Parental Study to Continue Receiving Treatment With SAR245408 or SAR245409 as a Monotherapy or as a Combination Regimen

ipd_sharing_description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

location_country:
United States
France
Spain
Belgium

location_facility:
Investigational Site Number 250003
Investigational Site Number 840104
Investigational Site Number 840006
Investigational Site Number 840022
Investigational Site Number 840008
Investigational Site Number 840020
Investigational Site Number 840004
Investigational Site Number 840021
Investigational Site Number 840007
Investigational Site Number 840009
Investigational Site Number 724001
Investigational Site Number 840010
Investigational Site Number 840018
Investigational Site Number 840015
Investigational Site Number 840017
Investigational Site Number 056001
Investigational Site Number 840002
Investigational Site Number 840005
Investigational Site Number 840003
Investigational Site Number 250004
Investigational Site Number 250005

summary:
Primary Objective:

The purpose of this study was to determine the long term safety and tolerability of SAR245408 and SAR245409 as a monotherapy or as part of a combination regimen in participants who were benefiting from treatment.


title: A Phase II, Open-Label, Randomized Study of MEDH7945A Versus Cetuximab in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck Who Have Progressed During or Following Platinum-based Chemotherapy

summary: This phase II, open-label, randomized study will evaluate the efficacy and safety of MEHD7945A versus cetuximab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck who have progressed during or following platinum-based chemotherapy. Patients will be randomized to receive either MEHD7945A 1100 mg intravenously (iv) every 2 weeks or cetuximab 400 mg/m2 iv loading dose followed by 250 mg/m2 iv weekly. Patients treated with cetuximab (Arm B) may cross-over to MEHD7945A (Arm A) upon central confirmation of progressive disease and upon meeting eligibility criteria. Anticipated time on study treatment is until disease progression or intolerable toxicity occurs.

lead_sponsor: Genentech, Inc.

location_country:
Romania
Spain
Italy
United Kingdom
Australia
Hungary
United States
France
Belgium
Germany
Bulgaria


acronym: GIOP

title: A Randomized, Double-blind, Active-controlled Study to Evaluate the Efficacy and Safety of Denosumab Compared With Risedronate in Glucocorticoid-treated Individuals

lead_sponsor: Amgen

ReferenceCitation: Saag KG, Wagman RB, Geusens P, Adachi JD, Messina OD, Emkey R, Chapurlat R, Wang A, Pannacciulli N, Lems WF. Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study. Lancet Diabetes Endocrinol. 2018 Jun;6(6):445-454. doi: 10.1016/S2213-8587(18)30075-5. Epub 2018 Apr 6.

ReferenceCitation: Saag KG, Pannacciulli N, Geusens P, Adachi JD, Messina OD, Morales-Torres J, Emkey R, Butler PW, Yin X, Lems WF. Denosumab Versus Risedronate in Glucocorticoid-Induced Osteoporosis: Final Results of a Twenty-Four-Month Randomized, Double-Blind, Double-Dummy Trial. Arthritis Rheumatol. 2019 Jul;71(7):1174-1184. doi: 10.1002/art.40874. Epub 2019 May 25.

location_country:
Denmark
Poland
Belgium
Spain
Russian Federation
Mexico
Netherlands
Argentina
Canada
Hungary
Korea, Republic of
United States
France
Colombia
Germany
Czechia

summary: This is a 2-year study to evaluate the effect of denosumab versus risedronate in adults with glucocorticoid-induced osteoporosis.