Congestive Heart Failure, Heart Failure, Heart Failure, Systolic, HFrEF - Heart Failure With Reduced Ejection Fraction
Conditions
Brief summary
It is believed that targeted SERCA2a enzyme replacement in HFrEF patients will correct defective intracellular Ca2+ hemostasis, resulting in improved cardiac contractile function and energetics which will, in turn, translate to improved clinical outcomes. Additionally, it is hypothesized that correcting SERCA2a dysfunction will also improve coronary blood flow through correction of the impaired endothelium-dependent nitric oxide-mediated vasodilatation observed in heart failure.
Detailed description
MUSIC-HFrEF1 is an interventional study of SRD-001, an adeno-associated virus serotype 1 (AAV1) vector expressing the transgene for sarco(endo)plasmic reticulum Ca2+ ATPase 2a isoform (SERCA2a), in anti-AAV1 neutralizing antibody (NAb) negative subjects with ischemic or non-ischemic cardiomyopathy and New York Heart Association (NYHA) class III/IV symptoms of heart failure with reduced ejection fraction (HFrEF). The Phase 1 trial is an open-label, uncontrolled study investigating two doses of SRD-001 at 3E13 and 4.5E13 viral genomes (vg) in 3-4 participants at each dose level. The Phase 2 trial is a randomized, double-blind, placebo-controlled trial with prospective assignment to a single dose of either SRD-001 or placebo in a 1:1 ratio and a total sample size of N=50.
Interventions
BIOLOGICALSRD-001
AAV1/SERCA2a
DRUGPlacebo
SRD-001 matching placebo
Sponsors
Sardocor Corp.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Chronic ischemic or non-ischemic cardiomyopathy * NYHA class III/IV * LVEF ≤35% * Guideline-directed medical therapy for heart failure; ICD Main
Exclusion criteria
* Restrictive cardiomyopathy, hypertrophic cardiomyopathy, acute myocarditis, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease or discrete left ventricular (LV) aneurysm * Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), mechanical circulatory support device (MCSD) or cardiac shunt * Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LVRS, conventional revascularization procedure or valvular repair in the 6 months following treatment * Likely need for an immediate heart transplant or MCSD implant due to hemodynamic instability * Inadequate hepatic and renal function * Diagnosis of, or treatment for, any cancer within the last 5 years except for basal cell carcinoma or carcinomas in situ where surgical excision was considered curative
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in symptomatic parameters | Baseline to Month 6 and Month 12 | New York Heart Association classification (I, II, III or IV) |
| Change from baseline in physical parameter | Baseline to Month 6 and Month 12 | Distance walked during the 6MWT |
| Change from baseline in LV function/remodeling | Baseline to Month 6 and Month 12 | Left ventricular end systolic volume (LVESV) as assessed by echocardiography |
| Rate of recurrent events | Baseline to Month 6 and Month 12 | HF-related hospitalization, ambulatory worsening heart failure, all-cause death, MCSD and transplant |
| Rate of adverse events | 6 and 12 months | Treatment-emergent adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects who complete the trial | 12 months | Those who complete the trial vs withdraw consent, are lost to follow-up, or withdrawn due to an AE or other reason |
| Incidence of abnormal findings from interrogation of implantable cardioverter defibrillator | Baseline to Month 6 and Month 12 | New arrhythmias |
| Concomitant medication use | 6 and 12 months | Changes in heart failure related medications |
| Incidence of abnormal laboratory test results | Baseline to Month 6 and Month 12 | Hematologic, serum chemistries, NT-proBNP and troponin |
| Incidence of abnormal ECG results | Baseline to Month 6 and Month 12 | New arrhythmias |
| Incidence of abnormal physical examination findings | Baseline to Month 6 and Month 12 | Change from baseline in physical examination findings |
Countries
United States
Contacts
Primary ContactCOO
Outcome results
None listed