Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Reduced Ejection Fraction (MUSIC-HFrEF1)

A Phase 1/2 Trial of the Safety and Efficacy of SRD-001 (AAV1/SERCA2a) in Subjects With Heart Failure With Reduced Ejection Fraction

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Congestive Heart Failure; Heart Failure, Systolic; HFrEF - Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Biological: SRD-001; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 57
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: COO; Phone Number: 858-752-2941; Email: info@sardocorcorp.com

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Recruiting
      • San Diego Cardiac Center
      • Principal Investigator: Brian Jaski, MD
      • Contact: Emma Burkhalter, RN; Phone Number: 858-244-6890; Email: eburkhalter@sdcardiac.com
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Principal Investigator: Richard Cheng, MD
      • Contact: Kaye Reambonanza; Phone Number: 415-514-6147; Email: Kaye.Reambonanza@ucsf.edu
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University in Saint Louis
      • Principal Investigator: Gregory Ewald, MD
      • Contact: Annie Dirks, RN, BSN; Phone Number: 314-454-8711; Email: aplatts@wustl.edu
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
      • Contact: Therese Villina, MPHI, BSN; Phone Number: 214-645-7083; Email: Therese.Vallina@utsouthwestern.edu
      • Principal Investigator: Justin Grodin, MD
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • University of Washington Medicine
      • Contact: Katherine Nassans; Phone Number: 206-543-6850; Email: Knassans@uw.edu
      • Principal Investigator: Kenta Nakamura, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; One-time intracoronary infusion	Drug: Placebo; SRD-001 matching placebo
Experimental: SRD-001; 3E13 or 4.5E13 vg; one-time intracoronary infusion	Biological: SRD-001; AAV1/SERCA2a; Other Names: MYDICAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in symptomatic parameters	New York Heart Association classification (I, II, III or IV)	Baseline to Month 6 and Month 12
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
Change from baseline in physical parameter	Distance walked during the 6MWT	Baseline to Month 6 and Month 12
Change from baseline in LV function/remodeling	Left ventricular end systolic volume (LVESV) as assessed by echocardiography	Baseline to Month 6 and Month 12
Rate of recurrent events	HF-related hospitalization, ambulatory worsening heart failure, all-cause death, MCSD and transplant	Baseline to Month 6 and Month 12
Rate of adverse events	Treatment-emergent adverse events	6 and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Concomitant medication use	Changes in heart failure related medications	6 and 12 months
Incidence of abnormal laboratory test results	Hematologic, serum chemistries, NT-proBNP and troponin	Baseline to Month 6 and Month 12
Incidence of abnormal ECG results	New arrhythmias	Baseline to Month 6 and Month 12
Incidence of abnormal physical examination findings	Change from baseline in physical examination findings	Baseline to Month 6 and Month 12
Incidence of abnormal findings from interrogation of implantable cardioverter defibrillator	New arrhythmias	Baseline to Month 6 and Month 12

Collaborators and Investigators

• Sponsor: Sardocor Corp.
• Collaborators: Covance

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: January 7, 2021
• First Submitted That Met QC Criteria: January 8, 2021
• First Posted (Actual): January 11, 2021

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 24, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Systolic
• Other Study ID Numbers: SRD-001-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No