A Phase IIB Randomized, Placebo-Controlled, Multicenter Study of the Comparative Efficacy and Safety of Administration of Allogeneic-MSC Versus Placebo in Patients With Non- Ischemic Dilated Cardiomyopathy
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Non-ischemic Dilated Cardiomyopathy
- Sponsor
- Joshua M Hare
- Enrollment
- 136
- Locations
- 8
- Primary Endpoint
- Change in LVEF
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
The purpose of this study is to evaluate the safety and effectiveness of an experimental drug called human allogeneic mesenchymal stem cell therapy.
Investigators
Joshua M Hare
Principal Investigator
University of Miami
Eligibility Criteria
Inclusion Criteria
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •Men and women aged 18 to 80 years (inclusive) at the time of signing the informed consent form.
- •Diagnosis of NIDCM with left ventricular ejection fraction ≤45%.
- •Appropriate guideline-directed optimal medical therapy for non-ischemic cardiomyopathy. At a minimum, subjects must be on beta blockers and angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) or Angiotensin Receptor Neprilysin Inhibitors (ARNI) or have appropriate medical indication precluding use of one or both of these agents. Subjects must be on a stable regimen for at least 30 days prior to the procedure. Dose titration is allowed.
- •Be a candidate for cardiac catheterization\*
- •Be willing to undergo DNA test.
Exclusion Criteria
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •Be eligible for or require standard-of-care surgical or percutaneous intervention for the treatment of non-ischemic dilated cardiomyopathy
- •Clinical manifestation of coronary artery disease (CAD) (e.g., chest pain and concomitant clinical findings such as electrocardiogram changes suggestive of coronary ischemia, myocardial infarction) or evidence of endocardial or transmural scar on cardiac MRI suggestive of undiagnosed CAD or history of percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Be indicated for or require coronary artery revascularization
- •Documented presence of epicardial stenosis of 70% or greater in one or more major epicardial coronary arteries
- •Valvular heart disease including 1) aortic valve prosthesis, mechanical mitral valve, and mitral valve clip; 2) severe aortic valve insufficiency/regurgitation within 12 months of consent\*
- •Aortic stenosis with valve area ≤ 1.5cm2\*
- •Cardiomyopathy due to acute Post-partum (within 6 months), Non-compaction\*, or Hypertrophic\* cardiomyopathy
- •Cardiomyopathy due to known toxin (e.g amyloid) Note: anthracycline induced cardiomyopathy will be allowed
- •QTc interval \> 550 ms on baseline electrocardiogram (ECG) (note: QTc interval is the interval between the start of the Q wave and the end of the T wave in the heart's electrical cycle)
- •Automated Implantable Cardioverter Defibrillator (AICD) appropriate firing or anti tachycardia pacing for ventricular tachycardia or ventricular fibrillation within 30 days prior to consent
Arms & Interventions
Genotype A administered with placebo Group
Participants whose blood genotyping resulted with Genotype A (absence of any variant/ presence of benign variant) and randomized to the placebo group will receive the placebo intervention.
Intervention: Placebo
Genotype A administered with hMSC Group
Participants whose blood genotyping resulted with Genotype A (absence of any variant/ presence of benign variant) and randomized to the treatment group will receive the hMSC intervention.
Intervention: allogeneic human mesenchymal stem cells (hMSCs)
Genotype B administered with placebo Group
Participants whose blood genotyping resulted with Genotype B (variants of uncertain significance) and randomized to the placebo group will receive the placebo intervention.
Intervention: Placebo
Genotype B administered with hMSC Group
Participants whose blood genotyping resulted with Genotype B (variants of uncertain significance) and randomized to the treatment group will receive the hMSC intervention.
Intervention: allogeneic human mesenchymal stem cells (hMSCs)
Genotype C administered with placebo Group
Participants whose blood genotyping resulted with Genotype C (pathogenic or likely pathogenic variants) and randomized to the placebo group will receive the placebo intervention.
Intervention: Placebo
Genotype C administered with hMSC Group
Participants whose blood genotyping resulted with Genotype C (pathogenic or likely pathogenic variants) and randomized to the treatment group will receive the hMSC intervention.
Intervention: allogeneic human mesenchymal stem cells (hMSCs)
Outcomes
Primary Outcomes
Change in LVEF
Time Frame: Baseline, 12 months
Change in Left Ventricular Ejection Fraction (LVEF) as assessed via cardiac Magnetic Resonance Imaging (MRI)
Secondary Outcomes
- Change in global ventricular strain(Baseline, 12 months)
- Left ventricular function concordance(12 months)
- Change in LVEDVI(Baseline, 12 months)
- Change in Exercise tolerance(Baseline, 12 months)
- Incidence of TE-SAEs(Day 30)
- Change in left regional strain(Baseline, 12 months)
- Change in LVESVI(Baseline, 12 months)
- Change in Maximal oxygen consumption (peak VO2)(Baseline, 12 months)
- Change in New York Heart Association (NYHA) Class(Baseline, 12 months)
- Percent change in flow mediated diameter(Baseline, 12 months)
- Change in EPC-CFU(Baseline, 12 months)
- Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) Score(Baseline, 12 months)
- Incidence of MACE(12 months)
- Change in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)(Baseline, 12 months)