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

Plain English Summary

A Study of the Efficacy and Safety of Danicamtiv in Participants With Symptomatic Genetic and Familial Dilated Cardiomyopathy is a Phase 3 clinical trial sponsored by Kardigan, Inc. studying Symptomatic Genetic Dilated Cardiomyopathy. Tests if danicamtiv can help people with genetic or familial dilated cardiomyopathy (DCM) by improving heart function and exercise capacity. For adults with DCM symptoms, aged 18 and older, who have a genetic or familial form of the condition. Participants take danicamtiv or placebo pills twice daily for 6 months and visit the clinic for evaluations and tests. Alternative treatments include standard heart failure medications, but this study aims to find a new, specific treatment for genetic and familial DCM. The trial aims to enroll 332 participants.

Official Summary

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

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if diagnosed with genetic or familial DCM, have symptoms, and are 18 years or older. Not eligible if have heart failure from other causes, recent heart events, unstable heart rhythms, or severe kidney issues. Age: 18 and older, Health: Stable heart failure symptoms, Genetic or familial DCM diagnosis. This trial is studying Symptomatic Genetic Dilated Cardiomyopathy, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures show how well danicamtiv improves heart function and exercise capacity, helping patients manage their condition better. The specific primary outcome measures are: Part 1: Change from Baseline (Day 1) to Week 26 in left atrial function index in Cohort 1 (26 weeks); Part 2: Change from Baseline (Day 1) to Week 26 in peak VO2 in Cohort 1 (26 weeks). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial is important as it aims to fill a treatment gap for genetic and familial DCM, a condition with no specific approved drugs. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Symptomatic Genetic Dilated Cardiomyopathy, where improved treatment options are needed.

Investor Insight

The large market size and unmet need for specific treatments for genetic and familial DCM make this trial significant, with a high approval probability. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you have a genetic or familial form of DCM and if you have stable symptoms. You will take pills twice daily and visit the clinic for regular checkups and tests. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 332 participants

Interventions

• DRUG: danicamtiv — Danicamtiv will be administrated twice daily for up to 26 weeks
• DRUG: Placebo — Placebo will be administrated twice daily for up to 26 weeks

Primary Outcomes

• Part 1: Change from Baseline (Day 1) to Week 26 in left atrial function index in Cohort 1 (26 weeks)
• Part 2: Change from Baseline (Day 1) to Week 26 in peak VO2 in Cohort 1 (26 weeks)

Secondary Outcomes

• Part 1: Change from Baseline (Day 1) to Week 26 in peak VO2 (26 weeks)
• Part 1: Association between response in left ventricular global longitudinal strain and/or left atrial function index after 2 weeks of active treatment with placebo-adjusted Week 26 response in peak VO2 (26 weeks)
• Part 1: Change from Baseline (Day 1) to Week 26 in left atrial function index in overall population (26 weeks)
• Part 1 and 2: Change from Baseline (Day 1) to Week 26 in left ventricular ejection fraction (26 weeks)
• Part 1 and 2: Change from Baseline (Day 1) to Week 26 in ventilatory efficiency (26 weeks)

Full Eligibility Criteria

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

Trial Locations

• University of Alabama Birmingham, Birmingham, Alabama, United States
• Cedars Sinai, Los Angeles, California, United States
• UCSF, San Francisco, California, United States
• MedStar Washington Hospital Center, Washington D.C., District of Columbia, United States
• Louisiana State University (LSU) Health Sciences Center, New Orleans, Louisiana, United States
• Brigham and Women's Hospital, Boston, Massachusetts, United States
• Henry Ford Health System, Detroit, Michigan, United States
• Mayo Clinic Rochester, Rochester, Minnesota, United States
• Washington University in St. Louis, St Louis, Missouri, United States
• University of Nebraska Medical Center, Omaha, Nebraska, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Genetic and familial dilated cardiomyopathy, heart failure, genetic heart diseases, familial heart diseases, cardiovascular diseases

More Symptomatic Genetic Dilated Cardiomyopathy Trials

View all Symptomatic Genetic Dilated Cardiomyopathy clinical trials