Clinical trial NCT04703842: Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Reduced Ejection Fraction
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Congestive Heart Failure
Heart Failure, Systolic
Heart Failure
HFrEF - Heart Failure With Reduced Ejection Fraction
Lead sponsor: Sardocor Corp.
Sponsor class: INDUSTRY
First posted: 2021-01-11
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change from baseline in symptomatic parameters
timeFrame: Baseline to Month 6 and Month 12
measure: Change from baseline in symptomatic parameters
timeFrame: Baseline to Month 6 and Month 12
measure: Change from baseline in physical parameter
timeFrame: Baseline to Month 6 and Month 12
measure: Change from baseline in LV function/remodeling
timeFrame: Baseline to Month 6 and Month 12
measure: Rate of recurrent events
timeFrame: Baseline to Month 6 and Month 12
measure: Rate of adverse events
timeFrame: 6 and 12 months
Secondary outcomes:
measure: Proportion of subjects who complete the trial
timeFrame: 12 months
measure: Concomitant medication use
timeFrame: 6 and 12 months
measure: Incidence of abnormal laboratory test results
timeFrame: Baseline to Month 6 and Month 12
measure: Incidence of abnormal ECG results
timeFrame: Baseline to Month 6 and Month 12
measure: Incidence of abnormal physical examination findings
timeFrame: Baseline to Month 6 and Month 12
measure: Incidence of abnormal findings from interrogation of implantable cardioverter defibrillator
timeFrame: Baseline to Month 6 and Month 12
Other outcomes:
Locations:
city: San Diego
country: United States
facility: San Diego Cardiac Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Saint Louis
country: United States
facility: Washington University in Saint Louis
state: Missouri
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: University of Washington Medicine
state: Washington
Study officials:
References: