Hypertrophic Cardiomyopathy Clinical Trials

SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM)
Status: Complete

SEQUOIA-HCM was a Phase 3 randomized, placebo-controlled, double-blind, multi-center clinical trial of aficamten in patients with symptomatic oHCM on background medical therapy for 24 weeks.

The primary endpoint was the effect of aficamten on change in peak oxygen uptake (pVO2) measured by cardiopulmonary exercise testing (CPET) from baseline to week 24. Secondary objectives included change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score from baseline to week 12 and week 24, the proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) functional class from baseline to week 12 and week 24, change in post-Valsalva left ventricular outflow tract gradient (LVOT-G) to week 12 and week 24, the proportion of patients with post-Valsalva LVOT-G <30 mmHg, and change in total workload during CPET to week 24.

MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM)
Status: Complete

MAPLE-HCM is a Phase 3, multi-center, randomized, double-blind active-comparator clinical trial of aficamten compared to metoprolol in patients with symptomatic obstructive HCM.

The primary endpoint is the change in peak oxygen uptake (pVO2) from baseline to Week 24 measured by cardiopulmonary exercise testing (CPET). Secondary endpoints include the change from baseline to Week 24 in Kansas City Cardiomyopathy Questionnaire (KCCQ) score, the proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) functional class, and changes in left ventricular mass index (LVMI), left atrial volume index (LAVI), post-Valsalva left ventricular outflow tract gradient (LVOT-G) and NT-proBNP.

ACACIA-HCM (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints In Adults with Non-Obstructive HCM)
Status: Complete

ACACIA-HCM is a Phase 3 randomized, placebo-controlled, double-blind, multi-center clinical trial designed to evaluate aficamten in patients with symptomatic nHCM.

The dual primary endpoints are change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score and change in maximal exercise performance (peak VO2) from baseline to Week 36. Secondary endpoints include the change from baseline to Week 36 in sub-maximal exercise performance (Ve/VCO2), the proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) functional class, changes in left atrial volume index (LAVI) and NT-proBNP. After the primary analysis at 36 weeks, patients will continue treatment with aficamten or placebo for up to 72 weeks to evaluate additional secondary and exploratory analyses including the time to first cardiovascular event. 

CEDAR-HCM (Clinical Evaluation of Dosing with Aficamten to Reduce Obstruction in a Pediatric Population in HCM)
Status: Enrolling

CEDAR-HCM is a multi-center, randomized, double-blind, placebo-controlled and open-label extension clinical trial to evaluate the efficacy, pharmacokinetics (PK) and safety of aficamten in a pediatric population with symptomatic obstructive hypertrophic cardiomyopathy (HCM).

The primary endpoint is the change in Valsalva left ventricular outflow tract gradient (LVOT-G) from baseline to Week 12. Secondary endpoints include the change from baseline to Week 12 in resting LVOT-G, New York Heart Association (NYHA) Functional Class, pharmacokinetics and cardiac biomarkers including NT-proBNP and hs-cTnI. 

FOREST-HCM (Follow-Up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM)
Status: Enrolling by invitation

FOREST-HCM (previously known as REDWOOD-HCM OLE) is an open-label extension clinical study designed to assess the long-term safety and tolerability of aficamten in patients with hypertrophic cardiomyopathy (HCM Disease). Eligible patients have completed participation in REDWOOD-HCM or SEQUOIA-HCM.

REDWOOD-HCM (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM)
Status: Complete

REDWOOD-HCM was a Phase 2, multi-center, randomized, placebo-controlled, double-blind, dose finding clinical trial of aficamten in patients with symptomatic HCM. The primary objective of the trial was to determine the safety and tolerability of aficamten.

The secondary objectives were to describe the concentration-response and dose-response relationship of aficamten on the resting and post-Valsalva left ventricular outflow tract gradient as measured by echocardiography during 10 weeks of treatment. Cohorts 1 and 2 enrolled 28 patients with symptomatic obstructive HCM taking background medications exclusive of disopyramide. Cohort 3 enrolled 13 patients with symptomatic obstructive HCM taking background medications including disopyramide. Cohort 4 enrolled 41 patients with non-obstructive HCM.