Danicamtiv in Symptomatic Genetic and Familial Dilated Cardiomyopathy

What is the Purpose of this Study?

The purpose of this study is to evaluate whether an experimental drug called danicamtiv improves heart function in adults with dilated cardiomyopathy compared to current standard treatment. DCM is a condition in which the heart muscle weakens and enlarges, making it harder for the heart to pump blood. Participants in this study will have genetic DCM (DCM caused by a change in genes) or familial DCM (first-degree family member diagnosed with DCM). Researchers aim to evaluate how well danicamtiv works to treat DCM, how safe it is to use, and how long it stays in the bloodstream. Study procedures include blood work and imaging, administration of danicamtiv or placebo (inactive substance), and regular follow-up visits to monitor heart function and safety. Danicamtiv could help address the underlying cause of DCM by increasing the function and amount of motor proteins in the heart (cardiac myosin). The increase in motor protein function may help improve both cardiac function and quality of life for participants with DCM.

Eligibility

1. Has a diagnosis of DCM due to probable disease-causing variants of MYH7, TTN, or other identified genetic DCM variants, or with familial DCM
2. Has New York Heart Association (NYHA) Class II-IV at Screening with stable symptoms for ≥1 month.
3. Has at least mild left ventricular enlargement (LVE) and has adequate acoustic windows to enable accurate TTEs according to the Echocardiography Core Laboratory.
4. Has a LVEF of ≤45%.

Key Inclusion Criteria:

1. Has a diagnosis of DCM due to probable disease-causing variants of MYH7, TTN, or other identified genetic DCM variants, or with familial DCM
2. Has New York Heart Association (NYHA) Class II-IV at Screening with stable symptoms for ≥1 month.
3. Has at least mild left ventricular enlargement (LVE) and has adequate acoustic windows to enable accurate TTEs according to the Echocardiography Core Laboratory.
4. Has a LVEF of ≤45%.
5. 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.
6. Has DCM not attributed to substance abuse, amyloidosis, sarcoidosis, or any other secondary form of cardiomyopathy per the Investigator.
7. 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

Key Exclusion Criteria:

1. Has heart failure with reduced ejection (HFrEF) caused primarily by ischemic heart disease, chronic valvulopathy, or another condition, as determined by the Investigator.
2. Recent (\<90 days) clinically significant cardiac events, including acute coronary syndrome, hemodynamically significant epicardial coronary disease (per Investigator), coronary revascularization (percutaneous coronary intervention \[PCI\] or coronary artery bypass graft \[CABG\]), or hospitalization for heart failure/intravenous (IV) diuretic use.
3. Presence of disqualifying cardiac rhythms that might interfere with reliable echocardiographic measurements of left ventricle (LV) function, as determined by the Investigator including: (a) inadequately rate-controlled atrial fibrillation, (b) ectopic beats (atrial, junctional or ventricular) of sufficient frequency (e.g. \> 10% of total beats) that the participant's cardiac rhythm is irregular potentially interfering with reliable echocardiographic measurements of LV function.
4. Unstable or untreated severe ventricular arrythmia (eg, ventricular tachycardia or ventricular fibrillation).
5. History of malignancy of any type within 5 years prior to Screening
6. Severe renal insufficiency (defined at the time of Screening as current estimated glomerular filtration rate \[eGFR\] \<15 mL/min/1.73m2 by simplified Modification of Diet in Renal Disease equation \[sMDRD\]).
7. History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the Investigator or Sponsor, would pose a risk to participant safety or interfere with the study evaluation
8. History of heart transplantation or anticipated heart transplantation in the next 6 months.
9. Ongoing or anticipated advanced cardiac interventions, including chronic IV inotropic therapy, planned cardiac resynchronization therapy (CRT) or major surgery, or current/anticipated ventricular assist device placement within 6 months
10. Clinically significant laboratory abnormalities at Screening

Show less

Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

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

Study Details

Disease Type/Condition

Other

Principal Investigator

Kransdorf, Evan

Age Group

Adult

Phase

II/III

IRB Number

STUDY00004460

ClinicalTrials.gov ID

NCT07210723

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org