This study is being performed to understand the effect of different doses of CK-3773274 on patients with hypertrophic cardiomyopathy (HCM).
This was a Phase 2, multi-center, randomized, placebo-controlled, double-blind, dose-finding study in participants with symptomatic HCM. The study consisted of 4 cohorts. For Cohorts 1 and 2, participants with obstructive HCM (oHCM) and not receiving disopyramide were randomized 2:1 to active or placebo treatment and received up to 3 escalating doses of aficamten (5, 10, and 15 mg once daily in Cohort 1 and 10, 20, and 30 mg once daily in Cohort 2) or placebo based on site-read echocardiographic guidance. Cohort 3 consisted of participants with oHCM whose background HCM therapy included disopyramide. All participants in Cohort 3 received up to 3 escalating doses of aficamten (5, 10, and 15 mg once daily) based on echocardiographic guidance. Cohort 4 consisted of participants with non-obstructive HCM (nHCM) on standard of care background therapy. Cohort 4 participants received up to 3 doses of aficamten (5, 10, and 15 mg once daily), titrated based on site-read echocardiographic guidance. In all 4 cohorts, treatment duration was 10 weeks with a 4-week follow-up period after the last dose.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
96
CK-3773274 tablets administered orally once daily
CK-3773274 tablets administered orally once daily
Placebo administered orally once daily
Cedar-Sinai Medical Center
Los Angeles, California, United States
Incidence of Adverse Events (AEs)
Participant incidence of reported AEs to determine the safety and tolerability of aficamten in participants with HCM.
Time frame: 14 weeks
Incidence of Left Ventricular Ejection Fraction (LVEF) < 50%
Participant incidence of LVEF \< 50% as assessed by the core laboratory assessment.
Time frame: 14 weeks
Incidence of Serious Adverse Events (SAEs)
Participant incidence of reported SAEs to determine the safety and tolerability of aficamten in participants with symptomatic HCM.
Time frame: 14 weeks
Slope of the Relationship of the Plasma Concentration of CK-3773274 to the Change From Baseline in the Resting Left Ventricular Outflow Track Gradient (LVOT-G)
Concentration-response relationship of CK-3773274 on the resting LVOT-G on echocardiogram over 10 weeks of treatment in participants with (oHCM) obstructive hypertrophic cardiomyopathy (oHCM) (Cohorts 1, 2, 3 only)
Time frame: Baseline and 10 weeks
Slope of the Relationship of the Plasma Concentration of CK-3773274 to the Change From Baseline in the Post-Valsalva LVOT-G
Concentration-response relationship of CK-3773274 on the post-Valsalva LVOT-G on echocardiogram over 10 weeks of treatment in participants with oHCM (Cohorts 1, 2, 3 only)
Time frame: Baseline and 10 Weeks
Change From Baseline in Resting LVOT-G Over Time as a Function of Dose.
Dose response relationship on resting LVOT-G of CK-3773274 in participants with oHCM (Cohorts 1, 2, 3 only)
Time frame: Baseline and 10 Weeks
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UCSF Medical Center
San Francisco, California, United States
Northwestern University
Evanston, Illinois, United States
Tufts Medical Center
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
Michigan Medicine - University of Michigan
Ann Arbor, Michigan, United States
Washington University School of Medicine
St Louis, Missouri, United States
New York University Langone Health Medical Center
New York, New York, United States
Carolinas Medical Center
Charlotte, North Carolina, United States
...and 12 more locations
Change From Baseline in Post-Valsalva LVOT-G Over Time as a Function of Dose.
Dose response relationship of CK-3773274 on post-Valsalva LVOT-G in participants with symptomatic oHCM (Cohorts 1, 2, 3 only)
Time frame: 10 weeks
Slope of the Relationship of the Plasma Concentration of CK-3773274 to the Change From Baseline in the Resting LVEF
Concentration-response relationship of CK-3773274 on LVEF over 10 weeks of treatment in participants with HCM
Time frame: Day 1 to End of Study (EOS) (Week 14)