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 Obstructio
- Conditions
- Hypertrophic cardiomyopathy and Left Ventricular Outflow Tract Obstructionthickened heart muscle10010394
- Registration Number
- NL-OMON54001
- Lead Sponsor
- Cytokinetics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
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: * Has LV hypertrophy and
non-dilated LV chamber in the absence of other cardiac disease and
* 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.
• NYHA Functional Class II or III at screening.
• Hemoglobin >=10g/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 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
• 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).
* Moderate-severe valvular aortic stenosis.
* 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 requiring 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. (This exclusion does not apply if atrial
fibrillation has been treated with anticoagulation and adequately
rate-controlled for >6 months.)
-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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint of the study is change in pVO2 by CPET from baseline to<br /><br>Week 24.</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score<br /><br>(KCCQ-CSS) from baseline to Week 12 and Week 24<br /><br>• Proportion of patients with >=1 class improvement in NYHA Functional Class<br /><br>from baseline to Week 12 and Week 24<br /><br>• Change in post-Valsalva LVOT-G from baseline to Week 12 and Week 24<br /><br>• Proportion of patients with post-Valsalva LVOT-G <30 mmHg at Week 12 and Week<br /><br>24<br /><br>• Change in total workload during CPET from baseline to Week 24</p><br>