Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy
Conditions
Interventions
Drug: Aficamten Oral Tablet
Drug: Placebo Oral Tablet
Experimental: Aficamten
Participants in this arm will receive a single daily oral dose of 5 mg, 10 mg, 15 mg, or 20 mg of aficamten with dose leve
Sponsors
Divanji Punagh
Eligibility
Inclusion criteria
Inclusion criteria: - Between 18-85 years of age - Body mass index =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 AND - Resting LVOT-G = 60% - Participants with a history of intracavitary obstruction are eligible. - NYHA class II or III - Respiratory exchange ratio of >= 1.00 at screening by cardiopulmonary exercise testing (CPET) and predicted peak oxygen uptake (pVO2) = 30 and = 300 pg/mL or NT-proBNP >= 900 pg/mL if in atrial fibrillation or atrial flutter OR - For Black participants, an NT-pro BNP >= 225 pg/mL or NT-proBNP >= 675 pg/mL if in atrial fibrillation or atrial flutter
Exclusion criteria
Exclusion criteria: - Significant valvular heart disease (per Investigator judgment) - Moderate or severe valvular aortic stenosis or fixed subaortic obstruction - Moderate or severe mitral regurgitation - Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics nHCM (e.g, Noonan syndrome, Fabry disease, amyloidosis) - Known current unrevascularized coronary artery stenosis of >= 70% or documented history of myocardial infarction. - History of LV systolic dysfunction (LVEF = 100 mmHg - Received prior treatment with aficamten - Received treatment with mavacamten within 3 months prior to screening (must be discussed with the medical monitor prior to screening) - Undergone septal reduction therapy < 6 months prior to screening - Is being considered for or is likely to be considered for heart transplant listing or left ventricular assist device placement during the study period - Paroxysmal or permanent atrial fibrillation is excluded only if: - rhythm restoring treatment (e.g., direct-current cardioversion, atrial fibrillation ablation procedure, or antiarrhythmic therapy) has been required <= 3 months prior to screening - rate control and anticoagulation have not been achieved for at least 3 months prior to screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dual primary endpoints of: - Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) [Time Frame: Baseline to Week 36] - Change in pVO2 from baseline to Week 36" | — |
Secondary
| Measure | Time frame |
|---|---|
| - Proportion of participants with >= 1 class improvement in NYHA Functional Class from baseline to Week 36 - Change in the composite of two Z-scores of CPET parameters from baseline to Week 36: - pVO2 (maximal exercise capacity) - VE/VCO2 slope (sub-maximal exercise capacity) - Change in NT-proBNP from baseline to Week 36 - Change in LAVI from baseline to Week 36 - Time to first event of cardiovascular death, heart transplantation or left ventricular assist device, aborted sudden cardiac death, non-fatal stroke, heart failure hospitalization, or cardiac arrhythmia (atrial fibrillation or ventricular tachyarrhythmia) requiring treatment or hospitalization) | — |
Countries
Argentina, Australia, Brazil, Canada, China, Colombia, Denmark, France, Germany, Greece, Hungary, Iceland, Israel, Italy, Japan, Netherlands, Poland, Portugal, Spain, United Kingdom, United States
Contacts
Public ContactClinical trial contact
ICON Clinical Research GK
Outcome results
None listed