Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Reduced Ejection Fraction

Heart Failure Clinical Trial

— MUSIC-HFrEF1  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04703842
• Other study ID #: SRD-001-1001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 23, 2021
• Est. completion date: December 2028

Study information

• Verified date: March 2024
• Source: Sardocor Corp.
• Contact: COO
• Phone: 858-752-2941
• Email: info[@]sardocorcorp.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 57
• Est. completion date: December 2028
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure
• Heart Failure, Systolic

Intervention

Biological:
• SRD-001
AAV1/SERCA2a

Drug:
• Placebo
SRD-001 matching placebo

Locations

Country	Name	City	State
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Washington University in Saint Louis	Saint Louis	Missouri
United States	San Diego Cardiac Center	San Diego	California
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington Medicine	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Sardocor Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in symptomatic parameters	New York Heart Association classification (I, II, III or IV)	Baseline to Month 6 and Month 12
Primary	Change from baseline in symptomatic parameters	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	Baseline to Month 6 and Month 12
Primary	Change from baseline in physical parameter	Distance walked during the 6MWT	Baseline to Month 6 and Month 12
Primary	Change from baseline in LV function/remodeling	Left ventricular end systolic volume (LVESV) as assessed by echocardiography	Baseline to Month 6 and Month 12
Primary	Rate of recurrent events	HF-related hospitalization, ambulatory worsening heart failure, all-cause death, MCSD and transplant	Baseline to Month 6 and Month 12
Primary	Rate of adverse events	Treatment-emergent adverse events	6 and 12 months
Secondary	Proportion of subjects who complete the trial	Those who complete the trial vs withdraw consent, are lost to follow-up, or withdrawn due to an AE or other reason	12 months
Secondary	Concomitant medication use	Changes in heart failure related medications	6 and 12 months
Secondary	Incidence of abnormal laboratory test results	Hematologic, serum chemistries, NT-proBNP and troponin	Baseline to Month 6 and Month 12
Secondary	Incidence of abnormal ECG results	New arrhythmias	Baseline to Month 6 and Month 12
Secondary	Incidence of abnormal physical examination findings	Change from baseline in physical examination findings	Baseline to Month 6 and Month 12
Secondary	Incidence of abnormal findings from interrogation of implantable cardioverter defibrillator	New arrhythmias	Baseline to Month 6 and Month 12