Efficacy and Safety of CK3773274 in Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction

What is the Purpose of this Study?

This study focuses on individuals who have obstructive hypertrophic cardiomyopathy (oHCM, a condition in which the heart muscle is abnormally thick) and who also have left ventricular outflow tract (LVOT) obstruction, a condition that interferes with the flow of blood from the heart to the body. The purpose of the study is to compare the effects of an experimental drug called CK-3773274 and placebo (inactive substance) on the exercise abilities and health status of patients with oHCM. The safety and tolerability of CK-3773274 will also be studied. CK-3773274 may reduce symptoms of oHCM by reducing LVOT obstruction. Researchers will measure the amount of CK-3773274 in the blood at various times, as well the effect of the drug on the patient’s oHCM. Throughout the study, participants will continue with their regular (standard-of-care) medications for oHCM. They will be randomly assigned to receive either CK-3773274 or placebo.

Eligibility

Males and females between 18 and 85 years of age, inclusive, at screening.
Body mass index <35 kg/m2.
Diagnosed with HCM per the following criteria:

Key Inclusion Criteria:

Males and females between 18 and 85 years of age, inclusive, at screening.
Body mass index <35 kg/m2.
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.

Key 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).
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 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.

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

A PHASE 3, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF CK3773274 IN ADULTS WITH SYMPTOMATIC HYPERTROPHIC CARDIOMYOPATHY AND LEFT VENTRICULAR OUTFLOW TRACT OBSTRUCTION

Study Details

Disease Type/Condition

Cardiomyopathy

Principal Investigator

Rader, Florian

Age Group

Adult

Phase

III

IRB Number

STUDY00001817

ClinicalTrials.gov ID

NCT05186818

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org