Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Reduced Ejection Fraction
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: SRD-001, Placebo.
- Who it may be relevant to
- Registry conditions: Congestive Heart Failure, Heart Failure, Systolic, Heart Failure, HFrEF - Heart Failure With Reduced Ejection Fraction. Basic parameters: 18 years — 80 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
A Phase 1/2 Trial of the Safety and Efficacy of SRD-001 (AAV1/SERCA2a) in Subjects With Heart Failure With Reduced Ejection Fraction
Overview
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
- Biological SRD-001
AAV1/SERCA2a - Drug Placebo
SRD-001 matching placebo
Primary outcome measures
- Change from baseline in symptomatic parameters [Time frame: Baseline to Month 6 and Month 12]
- Change from baseline in symptomatic parameters [Time frame: Baseline to Month 6 and Month 12]
- Change from baseline in physical parameter [Time frame: Baseline to Month 6 and Month 12]
- Change from baseline in LV function/remodeling [Time frame: Baseline to Month 6 and Month 12]
- Rate of recurrent events [Time frame: Baseline to Month 6 and Month 12]
- Rate of adverse events [Time frame: 6 and 12 months]
Secondary outcome measures (6)
- Proportion of subjects who complete the trial [Time frame: 12 months]
- Concomitant medication use [Time frame: 6 and 12 months]
- Incidence of abnormal laboratory test results [Time frame: Baseline to Month 6 and Month 12]
- Incidence of abnormal ECG results [Time frame: Baseline to Month 6 and Month 12]
- Incidence of abnormal physical examination findings [Time frame: Baseline to Month 6 and Month 12]
- Incidence of abnormal findings from interrogation of implantable cardioverter defibrillator [Time frame: Baseline to Month 6 and Month 12]
Eligibility 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Quadruple blind
- Primary purpose
- Treatment
Study locations
United States · 5 centers
- San Diego Cardiac Center — San Diego
- University of California, San Francisco — San Francisco
- Washington University in Saint Louis — St Louis
- University of Texas Southwestern Medical Center — Dallas
- University of Washington Medicine — Seattle
Identifiers
NCT: NCT04703842 · SRD-001-1001