A Phase 2b/3, Adaptive, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of Danicamtiv in Participants With Symptomatic Genetic and Familial Dilated Cardiomyopathy
The Sponsor is studying an investigational medication called danicamtiv to determine if it can help people with genetic and familial dilated cardiomyopathy (DCM). Investigational means that the safety and effectiveness of danicamtiv have not been established. Currently, there are no approved drugs that are designed specifically to treat genetic or familial DCM. The purpose of this study is to evaluate how well danicamtiv works compared to a placebo (sugar pill that looks like danicamtiv pill but does not contain any danicamtiv) and see how safe it is for people with genetic and familial DCM. In DCM, the heart muscle weakens and enlarges, making it harder for the heart to pump blood; this can happen for different reasons. Some people have DCM because of a change in a gene (called genetic DCM). Others may have DCM that runs in their family, even if no specific gene change is found (called familial DCM). The main goals of the study are: * To assess the effect of danicamtiv on cardiac function using echocardiogram. * To evaluate the impact of danicamtiv on exercise capacity * To evaluate the safety and tolerability of danicamtiv Participants will: * Take danicamtiv or placebo every day for approximately 6 months * Visit the clinic about 12 times for initial evaluation, checkups, tests and follow up
• Has a diagnosis of DCM due to probable disease-causing variants of MYH7, TTN, or other identified genetic DCM variants, or with familial DCM
• Has New York Heart Association (NYHA) Class II-IV at Screening with stable symptoms for ≥1 month.
• Has at least mild left ventricular enlargement (LVE) and has adequate acoustic windows to enable accurate TTEs according to the Echocardiography Core Laboratory.
• Has a LVEF of ≤45%.
• Is on stable doses of maximally tolerated standard-of-care heart failure (HF) therapies reflecting current guidelines for at least 4 weeks prior to the first visit.
• Has DCM not attributed to substance abuse, amyloidosis, sarcoidosis, or any other secondary form of cardiomyopathy per the Investigator.
• Can perform an upright cardiopulmonary exercise training (CPET) with a peak oxygen uptake (pV̇O2) of 80% or less of predicted for a healthy individual and respiratory exchange ratio (RER) of ≥1.05