title: Prospective, Randomized, Placebo-controlled, Double-blind, Multicenter, Parallel-group, 24-week Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension

summary: Study to evaluate if macitentan is efficient, safe and tolerable enough to be used for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH).

ReferenceCitation: Ghofrani HA, Simonneau G, D'Armini AM, Fedullo P, Howard LS, Jais X, Jenkins DP, Jing ZC, Madani MM, Martin N, Mayer E, Papadakis K, Richard D, Kim NH; MERIT study investigators. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study. Lancet Respir Med. 2017 Oct;5(10):785-794. doi: 10.1016/S2213-2600(17)30305-3. Epub 2017 Sep 11.

location_country:
Germany
Lithuania
Poland
Hungary
United Kingdom
Switzerland
Mexico
Belgium
Korea, Republic of
China
Thailand
Turkey
Czechia
Ukraine
Russian Federation
France

location_facility: Centre for PPH, Charles University , II Interni klinika1.LF a VFN

location_facility: Instituto Nacional de Cardiologia (INC) Ignacio Chavez

location_facility: Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital, Pulmonary Vascular Medicine

location_facility: Missionsärztliche Klinik gGmbH Akademisches Lehrkrankenhaus der Julius-Maximilians-Universität

location_facility: MAHARAJ NAKORN CHIANG MAI HOSPITAL, Department of Internal Medicine

location_facility: University Hospital Gasthuisberg / Interne Geneeskunde - I.G. Pneumologie

location_facility: Federal State Institution "Federal center of Heart, Blood and Endocrinology named after V.A.Almazov Rosmedtekhnologies"

location_facility: Lietuvos Sveikatos Mokslų Universiteto Ligoninės Kauno Klinikos Pulmonologijos-Imunologijos Klinika

location_facility: Beijing Chao-Yang Hospital-Department of Respiration

location_facility: Siriraj Hospital, Division of Respiratory Disease and Tuberculosis

location_facility: The General Hospital of Shenyang Military Region,Congenital Heart Disease Department

location_facility: Papworth Hospital NHS Trust, Pulmonary Vascular Diseases Unit

location_facility: Federal State Budgetary Institution "Scientific Research Institute of Systemic Problems of Cardiovascular Diseases", Siberian branch of RAMS

location_facility: Cardiovascular institute & Fuwai Hospital- Thrombus Center

location_facility: Federal State Budgetary Institution "Russian Cardiology Scientific and Production Complex" of the Ministry of Health Care of the Russian Federation

location_facility: Istanbul University İstanbul Faculty Medicine Pulmonology Department

location_facility: King Chulalongkorn Memorial Hospital, Division of Respiratory and Respiratory Critical Care Medicine

location_facility: Debreceni Egyetem Orvos- és Egészségtudományi Centrum, Kardiológiai Klinika

location_facility: Hôpital Européen Georges Pompidou Service de Pneumologie, soins intensifs et endoscopies bronchiques

location_facility: Thoraxklinik am Universitätsklinikum Heidelberg

location_facility: Lviv Regional Clinical Hospital, Cardiosurgery Department

location_facility: Wojewódzki Szpital Specjalistyczny w Lublinie im. Stefana Kardynała Wyszyńskiego SPZOZ Oddział Kardiologii - Pododdział Intensywnego Nadzoru Kardiologicznego

location_facility: The first affiliated hospital of guangzhou medical university-respiratory department

location_facility: Federal State Budgetary Institution "Research Institute for Cardiology" of Siberian Branch under the Russian Academy of Medical Sciences / Cardiovascular Surgery Department

location_facility: Severance Hospital, YonSei University Health System

location_facility: E.N.Meshalkin Novosibirsk State Research Institute Of Circulation Pathology Rosmedtechnology

location_facility: State Institute of Phthisiology and Pulmonology n.a. F.G. Yanovskiy of AMS Ukraine

location_facility: ngShanghai Pulmonary Hospital, Department of Pulmonary Circulation

location_facility: Wojewódzki Szpital Specjalistyczny we Wrocawiu


type: EudraCT Number

title: A Phase IIb, Randomized, Multi-Center, Double-Blind, Dose-Ranging Study to Evaluate the Efficacy and Safety of Clazakizumab in Subjects With Moderate to Severe Active Rheumatoid Arthritis Who Have Experienced an Inadequate Response to TNF Inhibitors

summary: The primary purpose of this study is to identify an appropriate dose of study medication.

study_start_date_type: Actual

status: Completed

study_completion_date_type: Actual

study_type: Interventional

design_allocation: Randomized

primary_purpose: Treatment

enrollment_type: Actual

lead_sponsor: CSL Behring

location_country:
Italy
Hungary
Argentina
Japan
Mexico
United States
South Africa
Canada
France

location_facility: Dr. Latha Naik Medical Professional Corporation

location_facility: Cincinnati Rheumatic Disease Study Group

location_facility: Cividino Medicine Professional Corporation

location_facility: Rheumatology Associates Of North Alabama, P.C.

location_facility: Arthritis & Rheumatology Center Of Oklahoma Pllc

location_facility: Joint And Muscle Medical Care And Research Institute (Jmmcri)

location_facility: Paramount Medical Research & Consulting, Llc

location_facility: Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.

intervention_type: Drug

lead_sponsor_type: industriel

status_simplified: Completed


acronym: RESPITE

lead_sponsor: Bayer

summary:
BAY63-2521 Riociguat leads to the relaxation of smooth muscle cells in pulmonary arteria and may also inhibit abnormal remodeling of lung blood vessels. In patients with pulmonary arterial hypertension Riociguat showed to reduce the pulmonary blood pressure and improved the right heart function without unacceptable side effects. Here dose of Riociguat will be adjusted over 8 weeks then a Maintenance Phase of 16 weeks follows. Patients with Pulmonary Arterial Hypertension treated with stable doses of Phosphodiesterase Type-5 Inhibitors (Eg Sildenafil, Tadalafil) not appropriately responding to therapy will be included. Based on previous evidence and on the different modes of action an improvement of exercise capacity, heart function and quality of life may be expected if PDE5i treatment is transitioned to riociguat.

Where Riociguat is pending market approval or reimbursement once the treatment phase is completed drug can be made available for another 18 months (Extended Drug Supply Phase - EDSP) under study conditions. Patients may also transition at the end of the maintenance period or any time during the EDSP to any program that is intended to provide riociguat until drug approval/reimbursement, e.g. a long-term extension study, compassionate use or named patient program. Study termination is also possible at any time.

ReferenceType: result

ReferenceCitation: Hoeper MM, Klinger JR, Benza RL, Simonneau G, Langleben D, Naeije R, Corris PA. Rationale and study design of RESPITE: An open-label, phase 3b study of riociguat in patients with pulmonary arterial hypertension who demonstrate an insufficient response to treatment with phosphodiesterase-5 inhibitors. Respir Med. 2017 Jan;122 Suppl 1:S18-S22. doi: 10.1016/j.rmed.2016.11.001. Epub 2016 Nov 5.

oa_host_type: publisher

evidence: open (via crossref license)

host_type: publisher

license: publisher-specific-oa

license_normalized: publisher-specific

version: publishedVersion

repositories_concat: closed

unpaywall_oa_status: hybrid

publisher_dissemination: Elsevier

ReferenceCitation: Hoeper MM, Simonneau G, Corris PA, Ghofrani HA, Klinger JR, Langleben D, Naeije R, Jansa P, Rosenkranz S, Scelsi L, Grunig E, Vizza CD, Chang M, Colorado P, Meier C, Busse D, Benza RL. RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphodiesterase-5 inhibitors. Eur Respir J. 2017 Sep 9;50(3):1602425. doi: 10.1183/13993003.02425-2016. Print 2017 Sep.

oa_colors: green hybrid

oa_host_type: publisher;repository

evidence: open (via free pdf)

license: cc-by-nc

license_normalized: cc-by-nc

evidence: oa repository (via OAI-PMH doi match)

host_type: repository

repository_institution: PubMed Central - Europe PMC

repository_normalized: PubMed Central

evidence: oa repository (via pmcid lookup)

license_normalized: no license

repositories_concat: PubMed Central

publisher_dissemination: European Respiratory Society

title: An Open-label, International, Multicenter, Single-arm, Uncontrolled, Phase IIIb Study of Riociguat in Patients With Pulmonary Arterial Hypertension (PAH) Who Demonstrate an Insufficient Response to Treatment With Phosphodiesterase-5 Inhibitors (PDE-5i)

source: euctr

location_country:
Germany
Italy
United Kingdom
Switzerland
Belgium
United States
Czechia
Canada
France


title: A Phase 2 Single Arm, Multicenter Trial to Evaluate the Efficacy of the BiTE Antibody Blinatumomab in Adult Subjects With Relapsed/Refractory Philadelphia Positive B-precursor Acute Lymphoblastic Leukemia (Alcantara Study)

summary: The primary objective is to evaluate the rate of complete remission/complete remission with partial hematological recovery (CRh*) in adults with relapsed/refractory Philadelphia chromosome positive (Ph+) B-precursor acute lymphoblastic leukemia (ALL) who receive blinatumomab.

ReferenceType: background

ReferenceCitation: Martinelli G, Boissel N, Chevallier P, Ottmann O, Gokbuget N, Topp MS, Fielding AK, Rambaldi A, Ritchie EK, Papayannidis C, Sterling LR, Benjamin J, Stein A. Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study. J Clin Oncol. 2017 Jun 1;35(16):1795-1802. doi: 10.1200/JCO.2016.69.3531. Epub 2017 Mar 29. Erratum In: J Clin Oncol. 2017 Aug 10;35(23):2722. J Clin Oncol. 2017 Aug 20;35(24):2856.

ReferenceCitation: Kuchimanchi M, Zhu M, Clements JD, Doshi S. Exposure-response analysis of blinatumomab in patients with relapsed/refractory acute lymphoblastic leukaemia and comparison with standard of care chemotherapy. Br J Clin Pharmacol. 2019 Apr;85(4):807-817. doi: 10.1111/bcp.13864. Epub 2019 Feb 18.

ReferenceCitation: Kantarjian HM, Zugmaier G, Bruggemann M, Wood BL, Horst HA, Zeng Y, Martinelli G. Impact of Blinatumomab Treatment on Bone Marrow Function in Patients with Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. Cancers (Basel). 2021 Nov 9;13(22):5607. doi: 10.3390/cancers13225607.

ReferenceCitation: Clements JD, Zhu M, Kuchimanchi M, Terminello B, Doshi S. Population Pharmacokinetics of Blinatumomab in Pediatric and Adult Patients with Hematological Malignancies. Clin Pharmacokinet. 2020 Apr;59(4):463-474. doi: 10.1007/s40262-019-00823-8.

ReferenceCitation: Martinelli G, Boissel N, Chevallier P, Ottmann O, Gokbuget N, Rambaldi A, Ritchie EK, Papayannidis C, Tuglus CA, Morris JD, Stein A. Long-term follow-up of blinatumomab in patients with relapsed/refractory Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukaemia: Final analysis of ALCANTARA study. Eur J Cancer. 2021 Mar;146:107-114. doi: 10.1016/j.ejca.2020.12.022. Epub 2021 Feb 13.

ReferenceCitation: Topp MS, Stein AS, Gokbuget N, Horst HA, Boissel N, Martinelli G, Kantarjian H, Bruggemann M, Chen Y, Zugmaier G. Blinatumomab as first salvage versus second or later salvage in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia: Results of a pooled analysis. Cancer Med. 2021 Apr;10(8):2601-2610. doi: 10.1002/cam4.3731. Epub 2021 Mar 18.

ReferenceType: derived

ReferenceCitation: Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.

evidence: oa journal (via doaj)

license: cc-by

license_normalized: cc-by

unpaywall_oa_status: gold

publisher_dissemination: Informa

ipd_sharing: No

lead_sponsor: Amgen

location_country:
Germany
Italy
United Kingdom
United States
France


title: A Phase 2, Open-label, Randomized Study to Evaluate the Safety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia

summary: This open-label study is to determine the safety and efficacy of momelotinib in participants with either polycythemia vera (PV) or essential thrombocythemia (ET) who have not yet received treatment with a Janus kinase (JAK) inhibitor.

status: Terminated

ReferenceCitation: Verstovsek S, Courby S, Griesshammer M, Mesa RA, Brachmann CB, Kawashima J, Maltzman JD, Shao L, Xin Y, Huang D, Bajel A. A phase 2 study of momelotinib, a potent JAK1 and JAK2 inhibitor, in patients with polycythemia vera or essential thrombocythemia. Leuk Res. 2017 Sep;60:11-17. doi: 10.1016/j.leukres.2017.05.002. Epub 2017 May 30.

license: cc-by-nc-nd

license_normalized: cc-by-nc-nd

version: acceptedVersion

repositories_concat: PubMed Central;University of Melbourne - Minerva Access

lead_sponsor: Sierra Oncology LLC - a GSK company

location_country:
Germany
Australia
United States
Canada
France

status_simplified: Unknown


intervention_type: Biological

acronym: PROgECT

lead_sponsor: Janssen Research & Development, LLC

summary: The purpose of this study is to evaluate the accuracy of a subset of the length-109 probe set panel (a genetic test) in predicting response to golimumab treatment in participants with moderately to severely active ulcerative colitis (UC).

ReferenceCitation: Li K, Strauss R, Marano C, Greenbaum LE, Friedman JR, Peyrin-Biroulet L, Brodmerkel C, De Hertogh G. A Simplified Definition of Histologic Improvement in Ulcerative Colitis and its Association With Disease Outcomes up to 30 Weeks from Initiation of Therapy: Post Hoc Analysis of Three Clinical Trials. J Crohns Colitis. 2019 Aug 14;13(8):1025-1035. doi: 10.1093/ecco-jcc/jjz022.

oa_host_type: closed

publisher_dissemination: Oxford University Press

ReferenceCitation: Telesco SE, Brodmerkel C, Zhang H, Kim LL, Johanns J, Mazumder A, Li K, Baribaud F, Curran M, Strauss R, Paxson B, Plevy S, Davison T, Knight L, Dibben S, Schreiber S, Sandborn W, Rutgeerts P, Siegel CA, Reinisch W, Greenbaum LE. Gene Expression Signature for Prediction of Golimumab Response in a Phase 2a Open-Label Trial of Patients With Ulcerative Colitis. Gastroenterology. 2018 Oct;155(4):1008-1011.e8. doi: 10.1053/j.gastro.2018.06.077. Epub 2018 Jul 4.

title: A Phase 2a Open-Label Study to Evaluate Prediction of Response to Golimumab Using a Transcriptomic Profile in Subjects With Moderately to Severely Active Ulcerative Colitis

type: Other Identifier

location_country:
France
Germany
Poland
Hungary
Netherlands
Belgium
United States
Ukraine
Bulgaria
Canada
Russian Federation
Czech Republic


title: A Double-blind, Randomized, Multicenter Study to Evaluate the Safety and Efficacy of Evolocumab, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor Due to Muscle Related Side Effects

summary: The primary objective of this study was to evaluate the effect of 24 weeks of evolocumab administered subcutaneously (SC) every month, compared with ezetimibe, on low-density lipoprotein cholesterol (LDL-C) levels in adults with high cholesterol who are unable to tolerate an effective dose of a statin due to muscle-related side effects (MRSE).

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: Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.

oa_host_type: repository

evidence: oa repository (via OAI-PMH title and first author match)

repository_institution: University College London - UCL Discovery

repository_normalized: UCL Discovery

repository_institution: University of Groningen / Centre for Information Technology - University of Groningen research database

repository_institution: London School of Hygiene and Tropical Medicine - LSHTM Research Online

unpaywall_oa_status: green

publisher_dissemination: Wiley

ReferenceCitation: Nissen SE, Stroes E, Dent-Acosta RE, Rosenson RS, Lehman SJ, Sattar N, Preiss D, Bruckert E, Ceska R, Lepor N, Ballantyne CM, Gouni-Berthold I, Elliott M, Brennan DM, Wasserman SM, Somaratne R, Scott R, Stein EA; GAUSS-3 Investigators. Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial. JAMA. 2016 Apr 19;315(15):1580-90. doi: 10.1001/jama.2016.3608.

unpaywall_oa_status: bronze

publisher_dissemination: American Medical Association

location_country:
Germany
Italy
New Zealand
Norway
United Kingdom
Denmark
Australia
Netherlands
United States
South Africa
Czechia
Canada
France


lead_sponsor: Hoffmann-La Roche

summary: This multicenter, randomized, open-label study will evaluate the efficacy, safety and tolerability of atezolizumab as monotherapy or in combination with bevacizumab versus sunitinib in participants with histologically confirmed, inoperable, locally advanced or metastatic renal cell carcinoma who have not received prior systemic therapy either in the adjuvant or metastatic setting.

ReferenceCitation: Pal SK, McDermott DF, Atkins MB, Escudier B, Rini BI, Motzer RJ, Fong L, Joseph RW, Oudard S, Ravaud A, Bracarda S, Suarez C, Lam ET, Choueiri TK, Ding B, Quach C, Hashimoto K, Schiff C, Piault-Louis E, Powles T. Patient-reported outcomes in a phase 2 study comparing atezolizumab alone or with bevacizumab vs sunitinib in previously untreated metastatic renal cell carcinoma. BJU Int. 2020 Jul;126(1):73-82. doi: 10.1111/bju.15058. Epub 2020 Apr 24.

location_facility: Klinikum d.Universität München Campus Großhadern

location_facility: Texas Oncology-Baylor Sammons Cancer Center

location_facility: Klinikum rechts der Isar der TU München; Klinikapotheke

location_facility: Tennessee Oncology PLLC - Nashville (20th Ave)

location_facility: Rocky Mountain Cancer Ctr - Denver (Williams)

location_facility: Cleveland Clinic Foundation; Taussig Cancer Center

location_facility: Yale Uni School of Medicine; Section of Medical Oncology

location_facility: Institut Gustave Roussy; Departement Oncologie Medicale

location_facility: HonorHealth Research Institute - Bisgrove

location_facility: Christie Hospital Nhs Trust; Medical Oncology

location_facility: Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie

location_facility: Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal

location_facility: Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale

location_facility: Prof. Dr. I. Chiricuta Institute of Oncology

location_facility: Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2

location_facility: Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica

location_facility: Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department

location_facility: City of Hope Comprehensive Cancer Center

title: A Phase II, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Administered as Monotherapy or in Combination With Bevacizumab Versus Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma

location_country:
Germany
Italy
Poland
United Kingdom
Romania
United States
Spain
Czechia
France


title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab for Previously Untreated Chronic Lymphocytic Leukemia

summary:
The primary objective of this study is to evaluate the progression-free survival in participants with previously untreated chronic lymphocytic leukemia (CLL) who would otherwise be suitable for bendamustine and rituximab treatment as standard of care.

An increased rate of deaths and serious adverse events (SAEs) among participants with front-line CLL and early-line indolent non-Hodgkin lymphoma (iNHL) treated with idelalisib in combination with standard therapies was observed by the independent data monitoring committee (DMC) during regular review of 3 Gilead Phase 3 studies. Gilead reviewed the unblinded data and terminated this study in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA).

ipd_sharing: Yes

ipd_sharing_description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.

lead_sponsor: Gilead Sciences

location_country:
Italy
Poland
Hungary
United Kingdom
Romania
Australia
Belgium
United States
Spain
Croatia
Czechia
Canada
France

location_facility: Centrum Onkologii-Instytut Marii Sklodowskiej -Curie klinika Nowotworow Ukladu Chlonnego

location_facility: St. Jude Heritage Healthcare Virginia K. Crosson Cancer Center

location_facility: University Hospital Southampton NHS Trust

location_facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center

location_facility: Royal Wolverhampton Hospital NHS Trust, New Cross Hospital

location_facility: Szegedi Tudomanyegyetem AOK - Szent-Gyorgyi Albert Klinikai Kozpont, II. Belgyógyászati Klinika

location_facility: Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu Klinika i Katedra Hematologii,Nowotworow Krwi i Transplantacji Szpiku

location_facility: East Kent Hospitals University NHS Foundation Trust

location_facility: University of Debrecen HSC Institute of internal Medicine, Department of Hematology

location_facility: Wojewodzki Szpital Specjalistyczny im. M. Kopernika Klinika Hematologii

location_facility: Emergency County Clinical Hospital Brasov

location_facility: Barwon Health, University Hospital Geelong

location_facility: Kaposi Mor Oktato Korhaz, Intezeti Gyogyszertar,

location_facility: Hematology /Oncology Associates of Northern New Jersey

location_facility: Dolnoslakie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku

location_facility: Centralny Szpital Kliniczny MSW w Warszawie Klinika Onkologii i Hematologii

location_facility: Azienda Ospedaliero Universitaria Policlinico di Modena

location_facility: Flinders Medical Centre, Department of Haematology, Level 6

location_facility: Franciscan Physician Network Oncology & Hematology

location_facility: CHU de Québec - Hôpital de l'Enfant-Jésus

location_facility: Royal Liverpool & Broadgreen Univ. Hospitals NHS Trust

location_facility: Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital

location_facility: Siouxland Hematology-Oncology Associates, LLP


type: Registry Identifier

title: A Multicenter, Single-arm, Open-label, Postmarketing Safety Study to Evaluate the Risk of Seizure Among Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated With Enzalutamide Who Are at Potential Increased Risk of Seizure

acronym: UPWARD

summary: The objective of this study was to evaluate the incidence of seizures and monitor the safety of enzalutamide treatment in participants with metastatic castration-resistant prostate cancer (mCRPC) known to have risk factor(s) for seizure.

ipd_sharing_description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

lead_sponsor: Astellas Pharma Global Development, Inc.

collaborators: Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

location_country:
Finland
Germany
New Zealand
Argentina
Australia
Chile
Czechia
Canada
France
Hungary
United States
Belgium
Italy
United Kingdom
Singapore
Sweden
Korea, Republic of
Spain
Taiwan
Israel

location_facility:
Site FI35802
Site TW88603
Site AU61002
Site US10016
Site US10008
Site US10026
Site IL97204
Site US10005
Site US10001
Site US10025
Site CL56003
Site NZ64001
Site BE32001
Site DE49003
Site KR82007
Site IT39002
Site FI35801
Site SE46001
Site ES34003
Site AR54004
Site KR82004
Site ES34006
Site BE32003
Site CA15014
Site AU61004
Site US10024
Site CA15005
Site FR33005
Site IL97208
Site IL97203
Site US10039
Site AR54006
Site CL56001
Site FI35803
Site DE49009
Site DE49001
Site AU61007
Site KR82003
Site HU36002
Site CZ42004
Site FR33004
Site IL97201
Site SG65002
Site ES34004
Site CA15001
Site AU61012
Site CL56002
Site AR54002
Site CA15004
Site IT39005
Site TW88601
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Site AU61005
Site IL97207
Site AR54003
Site CL56004
Site IL97202
Site US10014
Site KR82001
Site AR54001
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Site IL97205
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Site BE32004
Site AR54005
Site FR33002
Site CA15010
Site ES34005
Site IL97206
Site SE46002
Site GB44002
Site KR82006
Site AU61001
Site IT39003
Site IT39001
Site AU61011


lead_sponsor: AstraZeneca

summary: This is a 2-part study in patients with metastatic CRPC. Part A is an open-label safety run-in study to assess the safety, tolerability and pharmacokinetics (PK) of olaparib when given in addition to abiraterone 1000 mg once daily. Part B is a randomised, double-blind, placebo controlled comparison of the efficacy, safety and tolerability of the dose of olaparib selected from Part A when given in addition to abiraterone, versus placebo given in addition to abiraterone. Abiraterone is indicated in combination with prednisone or prednisolone for the treatment of patients with metastatic CRPC. Prednisone or prednisolone 5 mg twice daily (bid) will be administered with the abiraterone in this study.

ReferenceCitation: Clarke N, Wiechno P, Alekseev B, Sala N, Jones R, Kocak I, Chiuri VE, Jassem J, Flechon A, Redfern C, Goessl C, Burgents J, Kozarski R, Hodgson D, Learoyd M, Saad F. Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2018 Jul;19(7):975-986. doi: 10.1016/S1470-2045(18)30365-6. Epub 2018 Jun 4.

ReferenceCitation: Saad F, Thiery-Vuillemin A, Wiechno P, Alekseev B, Sala N, Jones R, Kocak I, Chiuri VE, Jassem J, Flechon A, Redfern C, Kang J, Burgents J, Gresty C, Degboe A, Clarke NW. Patient-reported outcomes with olaparib plus abiraterone versus placebo plus abiraterone for metastatic castration-resistant prostate cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol. 2022 Oct;23(10):1297-1307. doi: 10.1016/S1470-2045(22)00498-3. Epub 2022 Sep 2. Erratum In: Lancet Oncol. 2022 Oct;23(10):e446.

repository_institution: Cardiff University - ORCA Online Research @Cardiff

sponsor_collaborators:
AstraZeneca
Merck Sharp & Dohme LLC

title: A Randomised, Double-Blind, Placebo-Controlled, Multicentre Phase II Study to Compare the Efficacy, Safety and Tolerability of Olaparib Versus Placebo When Given in Addition to Abiraterone Treatment in Patients With Metastatic Castrate-Resistant Prostate Cancer Who Have Received Prior Chemotherapy Containing Docetaxel

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.

location_country:
Italy
Poland
United Kingdom
Netherlands
Belgium
United States
Spain
Czechia
Canada
Russian Federation
France


title: A Randomized, Double-blind, Placebo-controlled, Parallel-Group, 26-Week, Phase 3 Study of 2 Doses of EVP-6124 or Placebo in Subjects With Mild to Moderate Alzheimer's Disease Currently or Previously Receiving an Acetylcholinesterase Inhibitor Medication

summary: The purpose of this study is to evaluate the safety and efficacy of 2 fixed doses of EVP-6124 compared to placebo for 26 weeks in subjects with mild to moderate Alzheimer's disease currently receiving stable treatment or previously treated with an acetylcholinesterase inhibitor.

study_completion_date_type: Anticipated

lead_sponsor: FORUM Pharmaceuticals Inc

location_country:
France
Germany
Italy
United Kingdom
Argentina
Australia
Netherlands
Mexico
United States
Korea, Republic of
Spain
South Africa
Canada
Czech Republic


title: A Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Dose-response Study Evaluating the Efficacy and Safety of JNJ-54781532 in Subjects With Moderately to Severely Active Ulcerative Colitis

summary: The purpose of the study is to evaluate dose response of JNJ-54781532 in participants with moderately to severely active ulcerative colitis (UC).

ReferenceCitation: Sands BE, Sandborn WJ, Feagan BG, Lichtenstein GR, Zhang H, Strauss R, Szapary P, Johanns J, Panes J, Vermeire S, O'Brien CD, Yang Z, Bertelsen K, Marano C; Peficitinib-UC Study Group. Peficitinib, an Oral Janus Kinase Inhibitor, in Moderate-to-severe Ulcerative Colitis: Results From a Randomised, Phase 2 Study. J Crohns Colitis. 2018 Nov 9;12(10):1158-1169. doi: 10.1093/ecco-jcc/jjy085.

location_country:
Germany
Poland
Bulgaria
Hungary
Israel
Romania
Australia
Netherlands
Belgium
United States
Canada
Ukraine
Russian Federation
France


title: A Randomized, Open-label, Multicenter, Controlled, Parallel Arm, Phase III Study Assessing the Efficacy and Safety of AOP2014 vs. Hydroxyurea in Patients With Polycythemia Vera

acronym: PROUD-PV

summary: Phase III study to compare the efficacy and safety of the novel monopegylated interferon alpha 2b AOP2014 versus Hydroxyurea (the current licensed therapy for this disease). One year treatment of patients with polycythemia vera. Objective is to demonstrate non-inferiority of AOP2014 vs. HU in terms of disease response rate in both HU naïve and currently treated patients, diagnosed with Polycythemia Vera. Response is measured as normalisation of key lab parameters as well as normalized spleen size.

ReferenceCitation: Verger E, Soret-Dulphy J, Maslah N, Roy L, Rey J, Ghrieb Z, Kralovics R, Gisslinger H, Grohmann-Izay B, Klade C, Chomienne C, Giraudier S, Cassinat B, Kiladjian JJ. Ropeginterferon alpha-2b targets JAK2V617F-positive polycythemia vera cells in vitro and in vivo. Blood Cancer J. 2018 Oct 4;8(10):94. doi: 10.1038/s41408-018-0133-0.

oa_colors: green gold

publisher_dissemination: Springer-Nature

lead_sponsor: AOP Orphan Pharmaceuticals AG

sponsor_collaborators:
AOP Orphan Pharmaceuticals AG
PharmaEssentia (Co-Sponsor for USA)

location_country:
Germany
Italy
Poland
Slovakia
Hungary
Romania
Austria
Belgium
Spain
Bulgaria
Ukraine
Czech Republic
Russian Federation
France

location_facility: Multiprofile Hospital for Active Treatment "Sveta Marina"

location_facility: Independent Public Teaching Hospital No.1 in Lublin

location_facility: "Prof. Dr. Ion Chiricuta" Institute of Oncology

location_facility: Saint Cyril and Metod University Hospital Bratislava

location_facility: Samara Kalinin Regional Clinical Hospital

location_facility: Dnipropetrovsk City Multispecialty Clinical Hospital #4

location_facility: Emergency Clinical County Hospital Brasov

location_facility: University Multiprofile Hospital for Active Treatment "Sveti Georgi"

location_facility: St Istvan and St Laszlo Hospital of Budapest

location_facility: Specialized Hospital for Active Treatment of Hematological Diseases

location_facility: University of Szeged, Albert Szent-Gyorgyi Clinical Center, Koranyi fasor 6

location_facility: Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa, First Department of Internal Medicine

location_facility: Andrzej Mielecki Independent Public Clinical Hospital of Medical University of Silesia in Katowice

location_facility: National Research Center for Radiation Medicine, Institute of Clinical Radiology

location_facility: Hospital Clinic i Provincial de Barcelona

location_facility: Cherkasy Regional Oncology Center, Regional Treatment and Diagnostics Hematology Center

location_facility: University Hospital Carl Gustav Carus, Medical Clinic and Polyclinic I

location_facility: University Hospital with Outpatient Clinic F.D. Roosevelt

location_facility: Nicolaus Copernicus Municipal Specialist Hospital

location_facility: University Hospital Bonn, Center for Internal Medicine, Medical Clinic and Outpatient Clinic III

location_facility: O.F. Herbachevskyi Regional Clinical Hospital

location_facility: Institute of Blood Pathology and Transfusion Medicine

location_facility: Aachen University Hospital, Medical Clinic IV

location_facility: Institute of Hematology and Blood Transfusion

location_facility: Bekes County Pandy Kalman Hospital, 1st Department of Medicine, Hematology

location_facility: Fryderyk Chopin Provincial Specialized Hospital

location_facility: Institute of Hematology and Transfusion Medicine

location_facility: First Pavlov State Medical University of St. Petersburg


lead_sponsor: Ascendis Pharma A/S

summary: A six month study of ACP-001, a long-acting growth hormone product, versus standard human growth hormone therapy. ACP-001 will be given once-a-week, standard human growth hormone (hGH) will be given on a daily basis. The primary aim is to demonstrate safety, pharmacokinetics and pharmacodynamics over a period of six months. A secondary objective is the comparison of height velocity (HV) of the ACP-001 treated groups to the daily hGH treatment group.

ReferenceCitation: Chatelain P, Malievskiy O, Radziuk K, Senatorova G, Abdou MO, Vlachopapadopoulou E, Skorodok Y, Peterkova V, Leff JA, Beckert M; TransCon GH Working Group. A Randomized Phase 2 Study of Long-Acting TransCon GH vs Daily GH in Childhood GH Deficiency. J Clin Endocrinol Metab. 2017 May 1;102(5):1673-1682. doi: 10.1210/jc.2016-3776.

publisher_dissemination: The Endocrine Society

location_facility: Donetsk Regional Children Clinical Hospital

location_facility: Louis Turcanu Emergency Hospital for Children Timisoara

location_facility: Children's Memorial Health Institute Warsaw

location_facility: University Children's Hospital Magdeburg

location_facility: Institute of Endocrinology and Metabolism

location_facility: St. Spiridon County Clinic Emergency Hospital

location_facility: Children's Hospital of Athens "P. A. Kyriakou"

location_facility: University Multiprofile Hospital for Active Treatment (UMHAT) "Sv. Marina"

location_facility: St. Petersburg State Pediatric Medical Academy

location_facility: Ukrainian Children Specialized Clinical Hospital

title: A Multicenter, Phase 2, Randomized, Open Label, Active-controlled, Parallel-group Study Investigating the Safety, Tolerability, and Efficacy of Different Dose Levels of ACP-001 Administered Once Weekly Versus Standard Daily rhGH Replacement Therapy in Pre-pubertal Children With Growth Hormone Deficiency (GHD)

location_country:
Germany
Belarus
Poland
Russian Federation
Slovenia
Hungary
Romania
Greece
Turkey
Bulgaria
Ukraine
Czech Republic
Egypt
France


title: Phase Ib/II Multicenter Study of Buparlisib Plus Carboplatin or Lomustine in Patients With Recurrent Glioblastoma Multiforme

summary:
This is a multi-center, phase Ib/ II study (two parts) with patients that had recurrent glioblastoma multiforme. The first part (phase Ib) was to investigate the maximum tolerated dose/Recommended phase ll dose (MTD/RP2D) of once daily buparlisib in combination with every-three-week carboplatin or buparlisib once daily in combination with every-six-week lomustine (CCNU) using a Bayesian model. Once MTD/ RP2D is established in either of the 2 arms, the corresponding phase II portion of the study was to start. Phase II was to assess the treatment effect of buparlisib in combination with carboplatin in terms of Progression Free Survival (PFS) and was to compare the treatment effect of buparlisib with lomustine versus lomustine plus placebo in terms of PFS.

A preliminary assessment for both combinations (buparlisib plus carboplatin or lomustine) demonstrated that there was not enough antitumor activity compared to historical data with single agent carboplatin or lomustine. Based on the overall safety profile, and preliminary anti-tumor activity observed in this study, Novartis decided that no additional patients would be enrolled into this study. As a consequence, the Phase II part of the study was not conducted.

ReferenceCitation: Rosenthal M, Clement PM, Campone M, Gil-Gil MJ, DeGroot J, Chinot O, Idbaih A, Gan H, Raizer J, Wen PY, Pineda E, Donnet V, Mills D, El-Hashimy M, Mason W. Buparlisib plus carboplatin or lomustine in patients with recurrent glioblastoma: a phase Ib/II, open-label, multicentre, randomised study. ESMO Open. 2020 Jul;5(4):e000672. doi: 10.1136/esmoopen-2020-000672.

lead_sponsor: Novartis Pharmaceuticals

location_country:
Australia
Belgium
United States
Spain
Canada
France

location_facility: Barrow Neurological Insitute St. Joseph's Hospital

location_facility: MD Anderson Cancer Center/University of Texas


acronym: Dolutegravir Womens Study

lead_sponsor: ViiV Healthcare

summary: This study is designed to demonstrate the non-inferior antiviral activity of DTG/ABC/3TC fixed dose combination (FDC) once daily (OD) compared to atazanavir plus ritonavir (ATV+RTV) and tenofovir disoproxil fumarate/emtricitabine fixed dose combination (TDF/FTC FDC) OD in HIV-1 infected, ART-naïve women over 48 weeks. This study will also characterize the safety and tolerability of DTG/ABC/3TC FDC compared to ATV+RTV+TDF/FTC FDC. Sufficient number of subjects will be screened in order to ensure a total of approximately 474 subjects will be randomized (237 in each study arm)

ReferenceCitation: Orrell C, Hagins DP, Belonosova E, Porteiro N, Walmsley S, Falco V, Man CY, Aylott A, Buchanan AM, Wynne B, Vavro C, Aboud M, Smith KY; ARIA study team. Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA): week 48 results from a randomised, open-label, non-inferiority, phase 3b study. Lancet HIV. 2017 Dec;4(12):e536-e546. doi: 10.1016/S2352-3018(17)30095-4. Epub 2017 Jul 17. Erratum In: Lancet HIV. 2017 Dec;4(12 ):e535.

sponsor_collaborators:
ViiV Healthcare
GlaxoSmithKline

title: A Phase IIIb, Randomized, Open-label Study of the Safety and Efficacy of Dolutegravir/Abacavir/Lamivudine Once Daily Compared to Atazanavir and Ritonavir Plus Tenofovir/Emtricitabine Once Daily in HIV-1 Infected Antiretroviral Therapy Naïve Women

location_country:
Italy
Portugal
United Kingdom
Argentina
Mexico
United States
Spain
Thailand
South Africa
Canada
Puerto Rico
Russian Federation
France


title: A Randomised, Double-blind, Double-dummy, Active-controlled Study Evaluating the Efficacy, Safety and Tolerability of Twice-daily Aclidinium Bromide/Formoterol Fumarate Compared With Twice-daily Salmeterol/Fluticasone Propionate for 24 Weeks Treatment in Symptomatic Patients With Chronic Obstructive Pulmonary Disease (COPD)

summary: The purpose of the study is to compare the efficacy, safety and tolerability of aclidinium bromide/formoterol fumarate and salmeterol/fluticasone propionate in patients with chronic obstructive pulmonary disease (COPD)

ReferenceCitation: Vogelmeier C, Paggiaro PL, Dorca J, Sliwinski P, Mallet M, Kirsten AM, Beier J, Seoane B, Segarra RM, Leselbaum A. Efficacy and safety of aclidinium/formoterol versus salmeterol/fluticasone: a phase 3 COPD study. Eur Respir J. 2016 Oct;48(4):1030-1039. doi: 10.1183/13993003.00216-2016. Epub 2016 Aug 4.

oa_colors: green other

location_country:
Germany
Italy
Lithuania
Poland
Hungary
United Kingdom
Netherlands
Austria
Spain
South Africa
Bulgaria
Canada
Czech Republic
France


title: An Open-label, Multicenter, Multinational, Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of Repeated Biweekly Infusions of neoGAA in naïve and Alglucosidase Alfa Treated Late-onset Pompe Disease Patients.

summary:
Primary Objective:

To evaluate the safety and tolerability of neoGAA in treatment naïve and alglucosidase alfa treated late-onset Pompe disease patients.

Secondary Objective:

To evaluate the pharmacokinetics, pharmacodynamics of neoGAA in treatment naïve and alglucosidase alfa treated late-onset Pompe disease patients.

To evaluate the effect of neoGAA on exploratory efficacy endpoints in treatment naïve and alglucosidase alfa treated late-onset Pompe disease patients.

design_allocation: Non-Randomized

lead_sponsor: Genzyme, a Sanofi Company

location_country:
Germany
United Kingdom
Denmark
Netherlands
Belgium
United States
France

location_facility:
Investigational Site Number 208001
Investigational Site Number 840003
Investigational Site Number 276001
Investigational Site Number 840010
Investigational Site Number 826003
Investigational Site Number 276002
Investigational Site Number 840006
Investigational Site Number 250002
Investigational Site Number 840008
Investigational Site Number 250003
Investigational Site Number 840009
Investigational Site Number 250001
Investigational Site Number 528001
Investigational Site Number 840002
Investigational Site Number 056001
Investigational Site Number 276003
Investigational Site Number 840001


summary: This multicenter, randomized, double-blind, placebo-controlled study will evaluate the safety and efficacy of onartuzumab in combination with erlotinib in patients with previously untreated, unresectable stage IIIB or IV non-small cell lung cancer identified to carry and activating EGFR mutation and MET-positive. Patients will be randomized to receive either onartuzumab 15 mg/kg intravenously every 3 weeks in combination with erlotinib 150 mg orally daily or placebo in combination with erlotinib. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

title: A Randomized, Phase III, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Onartuzumab in Combination With Erlotinib as First-Line Treatment for Patients With MET-Positive Unresectable Stage IIIb or IV Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation

location_country:
Germany
Japan
United States
Korea, Republic of
Spain
Malaysia
Taiwan
France


title: A Blind Randomized Multicenter Study of Accelerated Fractionated Chemo-radiotherapy With or Without the Hypoxic Cell Radiosensitizer Nimorazole (Nimoral), Using a 15-gene Signature for Hypoxia in the Treatment of Squamous Cell Carcinoma of the Head and Neck.

summary:
The drug nimorazole belongs to a class of chemicals known as 5-nitroimidazoles. Drugs from this class are used against infection. In addition, nimorazole makes tumor cells more sensitive to radiotherapy.

Therefore, the investigators want to find out whether the addition of nimorazole to the standard treatment with radiotherapy in combination with chemotherapy with cisplatin shows activity against your type of head and neck cancer and is safe.

Furthermore the investigators will investigate if a specific examination done with your tumor tissue will help to predict whether the treatment will work or not.

To find out if the activity observed with this treatment is not caused by chance alone, the investigators need to obtain data from patients who receive this treatment and from patients who receive other treatments.

The data from these two groups of patients will be compared to see which treatment is better.

Participants will be split into 2 groups. Each group will receive different treatments. The treatment each group receives is determined by chance using a computer program. This works like flipping a coin and is called randomization. This helps to make sure that groups of patients are similar when the study starts. Neither you, your study doctor, nor the study staff can influence in which group you will be placed or which treatment you will receive.

If allocated to group 1, Patient will receive radiotherapy in combination with chemotherapy with cisplatin and nimorazole as a pill. This is considered the 'experimental' treatment.

If allocated to group 2, patient will receive radiotherapy in combination with chemotherapy with cisplatin and a so called 'placebo' as a pill. The placebo is a dummy treatment. It looks like the real one, but it is not. It contains no active ingredient/medicine.

status: Active, not recruiting

enrollment_type: Anticipated

lead_sponsor: European Organisation for Research and Treatment of Cancer - EORTC

location_country: Germany Poland Australia Netherlands Switzerland Belgium France

location_facility: Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet

location_facility: Princess Alexandra Hospital - University Of Queensland

location_facility: Radboud University Medical Center Nijmegen

location_facility: Maria Sklodowska-Curie Memorial Cancer Centre

location_facility: Hôpitaux universitaires de Genève - HUG - site de Cluse-Roseraie

location_facility: Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum

location_facility: Ludwig-Maximilians-Universitaet Muenchen - Klinikum der Universitaet Muenchen - Campus Grosshadern

status_simplified: Ongoing


title: A Phase Ib/II, Multicenter Study of the Combination of LEE011 and BYL719 With Letrozole in Adult Patients With Advanced ER+ Breast Cancer

summary:
The purpose of this trial is to inform the future clinical development of the two investigational agents in ER+ breast cancer, LEE011 (CDK4/6 inhibitor) and BYL719 (PI3K-alpha inhibitor).

This is a multi-center, open-label Phase Ib study. The Phase Ib dose escalation will estimate the MTD and/or RP2D for three regimens: two double combinations, LEE011 with letrozole and BYL719 with letrozole, followed by triple combinations of LEE011 + BYL719 with letrozole (Arms 3 and 4).

The Phase Ib dose escalation part will be followed by Phase Ib dose expansions to further characterize the safety, tolerability, PK and preliminary clinical anti-tumor activity of the combinations. Optional crossover for patients who have progressed while on dose escalation or dose expansion with doublet treatment on Arms 1 or 2 to be treated with the triplet combination (Arm 3) after the determination of the RP2D for Arm 3; is no longer permitted after protocol amendment 6.

Approximately 270 adult women with ER+/HER2- locally advanced or metastatic breast cancer will be enrolled.

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

location_facility: H Lee Moffitt Cancer Center and Research Institute H. Lee Moffitt Cancer Center

location_facility: Northwest Medical Specialties Northwest Medical Specialties

location_facility: Vanderbilt University Medical Center Vanderbilt - Thompson Ln

location_facility: University of California at San Diego, Moores Cancer Ctr Dept. of Moores Cancer Center


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, Cedres 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.

publisher_dissemination: American Society of Clinical Oncology (ASCO)

lead_sponsor: Verastem, Inc.

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

location_facility: Canterbury Regional Cancer & Haematology Service

location_facility: Kent Oncology Centre, Maidstone Hospital

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

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

location_facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

location_facility: University of California San Francisco Medical Center

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

location_facility: Universitaire Ziekenhuizen Leuven (University Hospitals Leuven)

location_facility: Institut Oncològic del Vallés Consorci Hospitalari Parc Tauli

location_facility: Centrum Pulmonologii Ii Torakochirurgii w Bystrej

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

location_facility: Iatros International / Bloemfontein Medi-Clinic


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.

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.

repository_institution: Ghent University - Ghent University Academic Bibliography

repositories:
PubMed Central
UCL Discovery
archive.ugent.be

repositories_institution: University College London - UCL Discovery

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.

publisher_dissemination: Frontiers

ReferenceCitation: Kvien TK, Conaghan PG, Gossec L, Strand V, Ostergaard 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.

repository_institution: University of Leeds, The University of Sheffield, University of York - White Rose Research Online

repository_institution: University of Oslo - Duo Research Archive

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_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

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


lead_sponsor: Allergan

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).

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

location_facility: William Beaumont Hospital Research Institute

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

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

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

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

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

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

location_country:
Italy
Poland
Belgium
United States
Turkey
Czechia
Canada
France


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: Unknown status

study_type: Observational

time_perspective: Prospective

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. doi: 10.1161/01.CIR.0000085167.67105.32. 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. doi: 10.1161/CIRCULATIONAHA.106.668681. 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.

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.

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. No abstract available.

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. No abstract available.

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. No abstract available.

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.

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, Cote M, Jimenez-Quevedo P, Macaya C, Pibarot P, Rodes-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.

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, Munoz-Garcia 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, Cote M, Pibarot P, Rodes-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 E, 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 E, Rodes-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. No abstract available.

ReferenceCitation: Dahou A, Toubal O, Clavel MA, Beaudoin J, Magne J, Mathieu P, Philippon F, Dumesnil JG, Puri R, Ribeiro HB, Larose E, Rodes-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):e003980. doi: 10.1161/JAHA.116.003980.

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, Senechal M, Dumesnil JG, Rosenhek R, Mathieu P, Larose E, Rodes-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, Thebault C, Dahou A, Ribeiro HB, Capoulade R, Mahjoub H, Urena M, Nombela-Franco L, Allende Carrera R, Clavel MA, Dumont E, Dumesnil J, De Larochelliere R, Rodes-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, Senechal M, Mundigler G, Burwash I, Ribeiro HB, O'Connor K, Mathieu P, Baumgartner H, Dumesnil JG, Rosenhek R, Larose E, Rodes-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, Senechal 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, Cote N, Mathieu P, Dumesnil JG, Audet A, Pepin A, Couture C, Fournier D, Trahan S, Page 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 E, Thompson C, De Larochelliere R, Moss R, Doyle D, Ribeiro HB, Urena M, Nombela-Franco L, Rodes-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, Marechaux 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. doi: 10.1007/BF00918487.

ReferenceCitation: Clavel MA, Burwash IG, Mundigler G, Dumesnil JG, Baumgartner H, Bergler-Klein J, Senechal 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.

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. doi: 10.1161/CIRCULATIONAHA.105.557678.

ReferenceCitation: Clavel MA, Webb JG, Rodes-Cabau J, Masson JB, Dumont E, De Larochelliere 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. doi: 10.1161/CIRCULATIONAHA.106.654210. 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 Larochelliere R, Doyle D, Masson JB, Bergeron S, Bertrand OF, Rodes-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, Rodes-Cabau J, Dumont E, Bagur R, Bergeron S, De Larochelliere 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, Senechal 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, Cote N, Dahou A, Bartko PE, Bergler-Klein J, Burwash IG, Orwat S, Baumgartner H, Mascherbauer J, Mundigler G, Fukui M, Cavalcante J, Ribeiro HB, Rodes-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.

repository_institution: Université Laval - CorpusUL

repositories_concat: PubMed Central;corpus.ulaval.ca

publisher_dissemination: Wolters Kluwer Health

ReferenceCitation: Dahou A, Clavel MA, Capoulade R, O'Connor K, Ribeiro HB, Cote N, Le Ven F, Rodes-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

sponsor_collaborators:
Laval University
University Hospital, Brest

location_country:
Germany
Austria
Belgium
United States
Canada
France

location_facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec

intervention_type: Other

lead_sponsor_type: academique


lead_sponsor: Amgen

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

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

location_facility: CHU Hotel Dieu - Service d'Hematologie Clinique

location_facility: University of Kansas Cancer Center and Medical Pavilion

location_facility: CHRU, Hopital Huriez - Department of Hematology

location_facility: H. Lee Moffitt Cancer Center & Research Institute

location_facility: Froedtert Hospital and the Medical College of Wisconsin

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

location_country:
United States
France


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.

ReferenceCitation: Sondergaard L, Rodes-Cabau J, Hans-Peter Linke A, Fichtlscherer S, Schafer 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.

lead_sponsor: Abbott Medical Devices

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

location_facility: UKE Hamburg (Universitatsklinik Eppendorf)

location_facility: Saint John Regional Hospital - New Brunswick Heart Centre

location_facility: Morriston hospital-ABM University Health Board

location_facility: Universitatsmedizin Berlin - Campus Benjamin Franklin (CBF)

location_facility: Herzzentrum Dresden GmbH Universitatsklinik

location_facility: Deutsches Herzzentrum Munchen des Freistaates Bayern

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

location_facility: Vilnius University Hospital Santarisku KLinikos

location_facility: Hospital Clinico Universitario Virgen de Arrixaca

location_facility: Institut de Cardiologie de Quebec (Hospital Laval)

location_facility: Fondazione Toscana Gabriele Monasterio - Ospedale del Cuore

location_facility: Immanuelklinikum Bernau und Herzzentrum Brandenburg

location_facility: Klinikum der Johann Wolfgang Goethe-Universitat Frankfurt

location_facility: Stadtisches Klinikum Karlsruhe gGmbH Medizinischen Klinik I

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

intervention_type: Device


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, Ryden 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.

evidence: open (via page says license)

repository_institution: Yonsei University Medical Library - YUHSpace

repository_institution: Seoul National University - Seoul National University Open Repository

publisher_dissemination: Korean Cancer Association

ReferenceCitation: Ahn MJ, Tsai CM, Shepherd FA, Bazhenova L, Sequist LV, Hida T, Yang JCH, Ramalingam SS, Mitsudomi T, Janne 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.

evidence: open (via free article)

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, Janne 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, Crino L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Janne 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, Janne 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, Janne 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, Janne 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, Johnstrom P, Varnas K, Malmquist J, Thress KS, Janne 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. doi: 10.1158/1078-0432.CCR-16-0399. Epub 2016 Jul 19.

publisher_dissemination: American Association for Cancer Research

ReferenceCitation: Oxnard GR, Thress KS, Alden RS, Lawrance R, Paweletz CP, Cantarini M, Yang JC, Barrett JC, Janne 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. No abstract available.

ReferenceCitation: Janne 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.

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


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


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, Inc.

location_country:
Germany
Netherlands
Austria
Switzerland
United States
Spain
Canada
France


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.

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


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


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


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

location_facility: ABMU Local Health Board, Morriston Hospital

location_facility: Alexian Brothers Center for Psychiatric Research

location_facility: Centrul Medical de Diagnostic si Tratament Ambulator Neomed

location_facility: Marmara University Pendik Training and Research Hospital

location_facility: The First Affiliated Hospital of Chongqing Medical University

location_facility: Saint George Hospital - University Medical Center

location_facility: Neurologicka ambulancia MUDr. Eva Gasparova

location_facility: LLC City Neurological Center "Sibneiromed"

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

location_facility: Shanghai Huashan Hospital, Neurology Department

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

location_facility: University Hospital Center Split, Clinic for Neurology

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

location_facility: Military Medical Academy - Multiprofile Hospital for Active Treatment

location_facility: GBOU VPO Smolensk State Medical University

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

location_facility: Derzhavna ustanova "Instytut nevrolohii, psykhiatrii ta narkolohii

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

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

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

location_facility: State Budgetary Healthcare Institution of Stavropol region

location_facility: The Barberry National Centre for Mental Health

location_facility: Oblasnyi klinichnyi tsentr neirokhirurhii ta nevrolohii,

location_facility: SPHI Leningrad Regional Psychoneurological Dispensary

location_facility: UZ Vitebsk Regional Childrens Clinical Centre

location_facility: Mangala Hospital & Mangala Kidney Foundation

location_facility: Dokuz Eylul Ün. Tip Fakültesi İç Hastalıkları

location_facility: NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS

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

location_facility: Multiprofile Hospital for Active Treatment Puls AD

location_facility: Instytut Medycyny Wsi im. Witolda Chodzki w Lublinie

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

location_facility: Ivano-Frankivska oblasna dytiacha klinichna likarnia

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

location_facility: Komunalnyi zaklad "Dnipropetrovska oblasna dytiacha klinichna likarnia"

location_facility: The First Bethune Hospital of Jilin University

location_facility: Cebu Doctors' University Hospital, Rm Ph 7

location_facility: Scott & White Memorial Hospital and Clinic

location_facility: Komunalne nekomertsiine pidpryiemstvo "Odeskyi oblasnyi

location_facility: Derzhavnyi zaklad "Ukrainskyi medychnyi tsentr reabilitatsii ditei z

location_facility: Komunalna ustanova "Odeska oblasna psykhiatrychna likarnia 2"

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

location_facility: University General Hospital of Thessaloniki "AHEPA"

location_facility: Semmelweis Egyetem, I. Sz. Gyermekgyogyaszati Klinika

location_facility: Institute for Child and Youth Healthcare of Vojvodina

location_facility: Celal Bayar University School of Medicine, Neurology Department

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

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

location_facility: Public Health Institution Hospital Dr Mladen Stojanovic

location_facility: Csongrad Megyei Egeszsegugyi Ellato Kozpont Hodmezovasarhely-Mako

location_facility: RSBHI Smolensk Regional Clinical Hospital

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

location_facility: SBHI of Saint Petersburg Psychoneurological Dispensary #5

location_facility: Regional State Budgetary Institution of Ministry of Health

location_facility: P D Hinduja National Hospital and Medical Research Centre

location_facility: Pediatric Epilepsy Center of Central Florida

location_facility: Eskisehir Osmangazi University Medical Faculty Department Of Neurology


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.

location_facility: St Jude s Childrens Research Hospital Dept of Oncology

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

location_facility: UCSF Medical Center Dept of Pediatic Oncology

location_facility: Childrens Healthcare of Atlanta Dept of Oncology

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

location_country:
Germany
United Kingdom
Australia
United States
France