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

Primary Purpose

Congestive Heart Failure, Heart Failure, Systolic, Heart Failure

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

SRD-001

Placebo

About this trial

This is an interventional treatment trial for Congestive Heart Failure

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

San Diego Cardiac CenterRecruiting
University of California, San FranciscoRecruiting
Washington University in Saint LouisRecruiting
University of Texas Southwestern Medical CenterRecruiting
University of Washington MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

SRD-001

Placebo

Arm Description

3E13 or 4.5E13 vg; one-time intracoronary infusion

One-time intracoronary infusion

Outcomes

Primary Outcome Measures

Change from baseline in symptomatic parameters

New York Heart Association classification (I, II, III or IV)

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

Change from baseline in physical parameter

Distance walked during the 6MWT

Change from baseline in LV function/remodeling

Left ventricular end systolic volume (LVESV) as assessed by echocardiography

Rate of recurrent events

HF-related hospitalization, ambulatory worsening heart failure, all-cause death, MCSD and transplant

Rate of adverse events

Treatment-emergent adverse events

Secondary Outcome Measures

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

Concomitant medication use

Changes in heart failure related medications

Incidence of abnormal laboratory test results

Hematologic, serum chemistries, NT-proBNP and troponin

Incidence of abnormal ECG results

New arrhythmias

Incidence of abnormal physical examination findings

Change from baseline in physical examination findings

Incidence of abnormal findings from interrogation of implantable cardioverter defibrillator

New arrhythmias

Full Information

NCT ID

NCT04703842

First Posted

January 7, 2021

Last Updated

July 31, 2023

Sponsor

Sardocor Corp.

1. Study Identification

Unique Protocol Identification Number

NCT04703842

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 1, 2021 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sardocor Corp.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Congestive Heart Failure, Heart Failure, Systolic, Heart Failure, HFrEF - Heart Failure With Reduced Ejection Fraction

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

57 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

SRD-001

Arm Type

Experimental

Arm Description

3E13 or 4.5E13 vg; one-time intracoronary infusion

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

One-time intracoronary infusion

Intervention Type

Biological

Intervention Name(s)

SRD-001

Intervention Description

AAV1/SERCA2a

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

SRD-001 matching placebo

Primary Outcome Measure Information:

Title

Change from baseline in symptomatic parameters

Description

New York Heart Association classification (I, II, III or IV)

Time Frame

Baseline to Month 6 and Month 12

Title

Change from baseline in symptomatic parameters

Description

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

Time Frame

Baseline to Month 6 and Month 12

Title

Change from baseline in physical parameter

Description

Distance walked during the 6MWT

Time Frame

Baseline to Month 6 and Month 12

Title

Change from baseline in LV function/remodeling

Description

Left ventricular end systolic volume (LVESV) as assessed by echocardiography

Time Frame

Baseline to Month 6 and Month 12

Title

Rate of recurrent events

Description

HF-related hospitalization, ambulatory worsening heart failure, all-cause death, MCSD and transplant

Time Frame

Baseline to Month 6 and Month 12

Title

Rate of adverse events

Description

Treatment-emergent adverse events

Time Frame

6 and 12 months

Secondary Outcome Measure Information:

Title

Proportion of subjects who complete the trial

Description

Those who complete the trial vs withdraw consent, are lost to follow-up, or withdrawn due to an AE or other reason

Time Frame

12 months

Title

Concomitant medication use

Description

Changes in heart failure related medications

Time Frame

6 and 12 months

Title

Incidence of abnormal laboratory test results

Description

Hematologic, serum chemistries, NT-proBNP and troponin

Time Frame

Baseline to Month 6 and Month 12

Title

Incidence of abnormal ECG results

Description

New arrhythmias

Time Frame

Baseline to Month 6 and Month 12

Title

Incidence of abnormal physical examination findings

Description

Change from baseline in physical examination findings

Time Frame

Baseline to Month 6 and Month 12

Title

Incidence of abnormal findings from interrogation of implantable cardioverter defibrillator

Description

New arrhythmias

Time Frame

Baseline to Month 6 and Month 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

COO

Phone

858-752-2941

info@sardocorcorp.com

Facility Information:

Facility Name

San Diego Cardiac Center

City

San Diego

State/Province

California

ZIP/Postal Code

92123

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Emma Burkhalter, RN

Phone

858-244-6890

eburkhalter@sdcardiac.com

First Name & Middle Initial & Last Name & Degree

Brian Jaski, MD

Facility Name

University of California, San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Justin Cortez

Phone

415-514-0527

justin.cortez@ucsf.edu

First Name & Middle Initial & Last Name & Degree

Richard Cheng, MD

Facility Name

Washington University in Saint Louis

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Annie Dirks, RN, BSN

Phone

314-454-8711

aplatts@wustl.edu

First Name & Middle Initial & Last Name & Degree

Gregory Ewald, MD

Facility Name

University of Texas Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Therese Villina, MPHI, BSN

Phone

214-645-7083

Therese.Vallina@utsouthwestern.edu

First Name & Middle Initial & Last Name & Degree

Justin Grodin, MD

Facility Name

University of Washington Medicine

City

Seattle

State/Province

Washington

ZIP/Postal Code

98195

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Katherine Nassans

Phone

206-543-6850

Knassans@uw.edu

First Name & Middle Initial & Last Name & Degree

Kenta Nakamura, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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