MUSIC-HFrEF1: Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Reduced Ejection Fraction
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
The CUPID-3 Trial 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 one dose of SRD-001 at 3E13 viral genomes (vg) in 4 to 8 subjects.
The Phase 2 is a randomized, double-blind, placebo-controlled trial with prospective assignment to a single dose of either SRD-001 at 3E13 vg or placebo in a 1:1 ratio and a total sample size of N=50.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SRD-001 3E13 vg; one-time intracoronary infusion |
Biological: SRD-001
AAV1/SERCA2a
Other Names:
|
| Placebo Comparator: Placebo One-time intracoronary infusion |
Drug: Placebo
SRD-001 matching placebo
|
Outcome Measures
Primary Outcome Measures
- 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 symptomatic parameters [Baseline to Month 6 and Month 12]
Quality of life as assessed by Kansas City Cardiomyopathy Questionnaire: 0-24, very poor to poor; 25-49, poor to fair; 50-74, fair to good; and 75-100, good to excellent
- 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 Outcome Measures
- 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
- 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
- Incidence of abnormal findings from interrogation of implantable cardioverter defibrillator [Baseline to Month 6 and Month 12]
New arrhythmias
Eligibility Criteria
Criteria
Main Inclusion Criteria:
-
Chronic ischemic or non-ischemic cardiomyopathy
-
NYHA class III/IV
-
LVEF ≤35%
-
Maximal, optimized heart failure therapy; 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | San Diego Cardiac Center | San Diego | California | United States | 92123 |
Sponsors and Collaborators
- Sardocor Corp.
- Covance
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SRD-001-1001