The purpose of this study is to evaluate the efficacy and safety of aficamten (CK-3773274) versus placebo in adults with symptomatic hypertrophic cardiomyopathy (HCM) and left ventricular outflow tract obstruction.
CY 6031 was a Phase 3, randomized, placebo-controlled, double-blind, multi-center trial in participants with symptomatic oHCM. Eligible participants were randomized in a 1:1 ratio to receive aficamten or placebo. Randomization was stratified by use of beta-blockers (yes or no) and cardiopulmonary exercise testing (CPET) exercise modality (treadmill or bicycle). Enrollment limits were applied as follows: participants taking beta-blockers were capped at approximately 70% of total enrollment; participants taking disopyramide were capped at approximately 10% of total enrollment; participants with persistent atrial fibrillation (AF) at screening were capped at approximately 15% of total enrollment; and participants using the bicycle CPET exercise modality were capped at approximately 50% of total enrollment. Investigational product (IP) was administered orally once daily (QD) with or without food for 24 weeks. During the initial 6 weeks of the treatment period, IP doses were individually titrated at Weeks 2, 4, and 6 based on echocardiography-guided criteria. Dose escalation at Weeks 2, 4, and 6 occurred only if a participant had a Valsalva left ventricular outflow tract gradient (LVOT-G) ≥ 30 mmHg and a biplane left ventricular ejection fraction (LVEF) ≥ 55%. Echocardiograms were performed at each subsequent visit during the trial, and the IP dose was down-titrated if the LVEF was \< 50%. The primary endpoint of peak oxygen uptake (pVO2) was measured by CPET at screening and at the end of treatment (Week 24). A participant's background HCM therapy was individually optimized according to local practice prior to enrollment in the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
282
Aficamten tablets were administered orally once daily.
Placebo tablets were administered orally once daily.
Change From Baseline in pVO2 at Week 24
The effect of CK-3773274 on exercise capacity in participants with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) was determined through changes in peak oxygen uptake (pVO2) after 24 weeks of treatment. pVO2 was measured by cardiopulmonary exercise testing (CPET) on a treadmill or bicycle. A higher pVO2 indicates better cardiorespiratory fitness.
Time frame: Baseline to Week 24
Change From Baseline in KCCQ-CSS at Week 24
The effect of aficamten on patient health status was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a patient-reported outcome designed to assess the physical limitations, symptoms, self-efficacy, social limitation, and quality of life of patients with heart failure symptoms. The KCCQ-Clinical Symptoms Score (KCCQ-CSS) is scored on a scale from 0 to 100, with higher scores indicating better physical functioning and symptoms.
Time frame: Baseline to Week 24
Change From Baseline in KCCQ-CSS at Week 12
The effect of aficamten on patient health status was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a patient-reported outcome designed to assess the physical limitations, symptoms, self-efficacy, social limitation, and quality of life of patients with heart failure symptoms. The KCCQ-Clinical Symptoms Score (KCCQ-CSS) is scored on a scale from 0 to 100, with higher scores indicating better physical functioning and symptoms.
Time frame: Baseline to Week 12
Proportion of Participants With ≥1 Class Improvement in New York Heart Association (NYHA) Functional Class From Baseline to Week 24
The effect of aficamten on NYHA functional classification was evaluated through changes observed from baseline through 24 weeks of treatment.
Time frame: Baseline to Week 24
Proportion of Participants With ≥1 Class Improvement in NYHA Functional Class From Baseline to Week 12
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Alaska Heart and Vascular Institute
Anchorage, Alaska, United States
UC San Diego Health - Sulpizio Cardiovascular Center
La Jolla, California, United States
Cedars-Sinai Medical Center - Smidt Heart Institute Clinic
Los Angeles, California, United States
University of California San Francisco
San Francisco, California, United States
Stanford University Hospital
Stanford, California, United States
Yale School of Medicine
New Haven, Connecticut, United States
Yale University School of Medicine
New Haven, Connecticut, United States
MedStar Washington Hospital Center
Washington D.C., District of Columbia, United States
Holy Cross Hospital / Cardiology Associates
Fort Lauderdale, Florida, United States
Mayo Clinic Florida
Jacksonville, Florida, United States
...and 104 more locations
The effect of aficamten on NYHA functional classification was evaluated through changes observed from baseline through 12 weeks of treatment.
Time frame: Baseline to Week 12
Change From Baseline in Valsalva Left Ventricular Outflow Tract Gradient (LVOT-G) at Week 24
The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 24.
Time frame: Baseline to Week 24
Change From Baseline in Valsalva LVOT-G at Week 12
The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 12.
Time frame: Baseline to Week 12
Proportion of Participants With Valsalva LVOT G <30 mmHg at Week 24
The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 24.
Time frame: Baseline to Week 24
Proportion of Participants With Valsalva LVOT G <30 mmHg at Week 12
The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 12.
Time frame: Baseline to Week 12
Duration of SRT Eligibility During the 24-week Treatment Period for Participants Who Were SRT Eligible at Baseline
The effect of aficamten treatment on the duration of septal reduction therapy (SRT) eligibility was evaluated over the 24- week treatment period.
Time frame: Baseline to Week 24
Change From Baseline to Week 24 in Total Workload During CPET
Effect of aficamten on intensity of exercise (based on speed, incline, participant weight, etc.) during CPET. Workload is an indication of the energy expended during the exercise test.
Time frame: Baseline to Week 24