Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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21 May 2024 |
Main ID: |
EUCTR2021-003536-92-PL |
Date of registration:
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20/04/2022 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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A Phase 3 trial to measure how safe and effective CK-3773274 is in Adults with obstructive hypertrophic cardiomyopathy (oHCM)
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Scientific title:
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A Phase 3, Multi-Center, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of CK-3773274 in Adults with Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction |
Date of first enrolment:
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30/05/2022 |
Target sample size:
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282 |
Recruitment status: |
Not Recruiting |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-003536-92 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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China
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Czech Republic
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Czechia
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Denmark
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France
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Germany
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Hungary
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Israel
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Italy
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Netherlands
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Poland
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Portugal
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Spain
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United Kingdom
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United States
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Contacts
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Name:
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Medical Affairs
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Address:
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350 Oyster Point Boulevard
94080
South San Francisco CA
United States |
Telephone:
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+16506242929 |
Email:
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medicalaffairs@cytokinetics.com |
Affiliation:
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Cytokinetics, Incorporated |
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Name:
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Medical Affairs
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Address:
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350 Oyster Point Boulevard
94080
South San Francisco CA
United States |
Telephone:
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+16506242929 |
Email:
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medicalaffairs@cytokinetics.com |
Affiliation:
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Cytokinetics, Incorporated |
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Key inclusion & exclusion criteria
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Inclusion criteria: - Males and females between 18 and 85 years of age, inclusive, at screening. - Body mass index <35 kg/m^2. - Diagnosed with HCM per the following criteria: a. Has LV hypertrophy and non-dilated LV chamber in the absence of other cardiac disease and b. Has an end-diastolic LV wall thickness as measured by the echocardiography core laboratory of: • =15 mm in one or more myocardial segments OR • =13 mm in one or more wall segments and a known-disease-causing gene mutation or positive family history of HCM - Has resting LVOT-G =30 mmHg and post-Valsalva LVOT-G =50 mmHg during screening as determined by the echocardiography core laboratory - LVEF =60% at screening as determined by the echocardiography core laboratory. - New York Heart Association (NYHA) Functional Class II or III at screening - Hemoglobin =10 g/dL at screening. - Respiratory exchange ratio (RER) =1.05 and pVO2 =90% predicted on the screening CPET per the core laboratory. - Patients on beta-blockers, verapamil, diltiazem, or disopyramide should have been on a stable doses for >6 weeks prior to randomization and anticipate remaining on the same medication regimen during the trial. Patients treated with disopyramide must also be concomitantly treated with a beta blocker and/or calcium channel blocker. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 169 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 113
Exclusion criteria: - Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis). - Significant valvular heart disease (per investigator judgment). a) Moderate-severe valvular aortic stenosis. b) Moderate-severe mitral regurgitation not due to systolic anterior motion of the mitral valve. - History of LV systolic dysfunction (LVEF <45%) or stress cardiomyopathy at any time during their clinical course. - Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations). - Has been treated with septal reduction therapy (surgical myectomy or percutaneous alcohol septal ablation) or has plans for either treatment during the trial period. - Documented paroxysmal atrial fibrillation during the screening period. - Paroxysmal or permanent atrial fibrillation is only excluded IF: • rhythm restoring treatment (eg, direct-current cardioversion, atrial fibrillation ablation procedure, or antiarrhythmic therapy)has been required =6 months prior to screening. • rate control and anticoagulation have not been achieved for at least 6 months prior to screening.
- History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening. - Has received prior treatment with CK-3773274 or mavacamten. Exclusion Criteria for CMR Sub-study - Inability to tolerate CMR. - Has an implantable cardioverter-defibrillator (ICD). - Has a cardiac pacemaker.
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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obstructive hypertrophic cardiomyopathy (oHCM) MedDRA version: 27.0
Level: PT
Classification code 10020871
Term: Hypertrophic cardiomyopathy
System Organ Class: 10010331 - Congenital, familial and genetic disorders
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Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
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Intervention(s)
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Product Name: aficamten Product Code: CK-3773274 Pharmaceutical Form: Film-coated tablet INN or Proposed INN: aficamten CAS Number: 2364554-48-1 Current Sponsor code: CK-3773274 Other descriptive name: (R)-N-(5-(5-ETHYL-1,2,4-OXADIAZOL-3-YL)-2,3-DIHYDRO-1H-INDEN-1-YL)-1-METHYL-1H-PYRAZOLE-4-CARBOXAMIDE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5- Pharmaceutical form of the placebo: Film-coated tablet Route of administration of the placebo: Oral use
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Primary Outcome(s)
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Primary end point(s): • Change in peak oxygen uptake (pVO2) by cardiopulmonary exercise testing (CPET)
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Secondary Objective: - To evaluate the effect of CK-3773274 on patient health status - To evaluate the effect of CK-3773274 on New York Heart Association (NYHA) Functional Classification - To evaluate the effect of CK-3773274 on post-Valsalva left ventricular outflow tract gradients (LVOT-G) - To evaluate the effect of CK-3773274 on exercise capacity - To evaluate the effect of CK-3773274 on duration of eligibility for septal reduction therapy
Safety To evaluate the safety and tolerability profile of CK-3773274 in patients with symptomatic oHCM
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Main Objective: - To evaluate the effect of CK-3773274 on exercise capacity in patients with symptomatic oHCM
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Timepoint(s) of evaluation of this end point: from baseline to Week 24
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Secondary Outcome(s)
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Timepoint(s) of evaluation of this end point: KCCQ-CSS - baseline to Week 12 and Week 24 NYHA Functional Class -baseline to Week 12 and Week 24 Change in post-Valsalva LVOT-G - baseline to Week 12 and Week 24 Proportion of patients with post-Valsava LVOT-G <30 mmHg - Week 12 and Week 24 Total workload during CPET - baseline to Week 24 Duration of eligibility for SRT - baseline to Week 24 Safety - Throughout the study
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Secondary end point(s): • Change in Kansas City Cardiomyopathy Questionnaire – Clinical Summary Score (KCCQ-CSS) • Proportion of patients with =1 class improvement in NYHA Functional Class • Change in post-Valsalva LVOT-G • Proportion of patients with post-Valsalva LVOT-G <30 mmHg • Change in total workload during CPET • Duration of eligibility for septal reduction therapy (SRT) in patients who are eligible for SRT at baseline
Safety • Incidence of reported major adverse cardiac events (cardiovascular [CV] death, cardiac arrest, non-fatal stroke, non-fatal myocardial infarction, CV hospitalization) • Incidence of new onset persistent atrial fibrillation • Incidence of appropriate implantable cardiac defibrillator (ICD) discharges and aborted sudden cardiac death • Incidence of left ventricular ejection fraction (LVEF) <50% • Incidence of treatment emergent adverse events
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Secondary ID(s)
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CY6031
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2021-003536-92-HU
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NCT05186818
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Source(s) of Monetary Support
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Cytokinetics, Incorporated
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Ethics review
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Status: Approved
Approval date: 25/04/2022
Contact:
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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