Modulation of SERCA2a of Intra-Myocytic Calcium Trafficking in Cardiomyopathy Secondary to Duchenne Muscular Dystrophy (MUSIC-DMD)

A Phase 1b, Open-Label, Controlled Trial Evaluating the Safety and Efficacy of SRD-001 (AAV1/SERCA2a) in Subjects With Cardiomyopathy Secondary to Duchenne Muscular Dystrophy

This research study is testing whether an experimental drug, called SRD-001, is safe and helps the weakened heart of patients with Duchenne muscular dystrophy (DMD) regain its ability to effectively pump blood to the rest of the body. SRD-001 is a form of gene therapy. The goal of SRD-001 gene therapy is to provide the heart muscle cells with extra copies of the SERCA2a gene so that they can produce more SERCA2a protein to help the heart muscle cells squeeze/contract better. Researchers will compare SRD-001 treated participants with no-treatment participants; all participants will continue to take their current heart medications. All participants will be followed very closely for 2 years and undergo cardiac magnetic resonance imaging of their heart at baseline, year 1 and year 2 along with assessment of upper limb function and lung function. After the 2 years of close follow-up, all participants will roll over into long-term follow-up where they will be called biannually for information on their current medical status.

Study Overview

• Status: Not yet recruiting
• Conditions: DMD-Associated Dilated Cardiomyopathy
• Intervention / Treatment: Genetic: SRD-001

Detailed Description

This phase 1b, multi-center, non-randomized, open-label, ascending dose escalation, no-intervention-control trial will assess the safety and explore the efficacy of SRD-001 administered as a one-time antegrade epicardial coronary artery infusion for the treatment of participants with cardiomyopathy secondary to DMD. SRD-001 is an AAV1 vector expressing the transgene for SERCA2a. Twelve participants will be assigned to either active treatment with SRD-001 or no-intervention based upon their neutralizing antibody status. The objectives of the trial are (1) to evaluate the safety of a one-time intracoronary administration of SRD-001 in participants with cardiomyopathy due to DMD; and (2) to explore the impact of SRD-001 on heart and skeletal muscle function and quality of life. After screening to determine eligibility, participants will be sequentially assigned to low dose SRD-001, high dose SRD-001 or no-intervention. Participants assigned to active treatment with SRD-001 will under cardiac catheterization and angiography just prior to the intracoronary infusion of SRD-001 and spend overnight int he hospital for observation.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sardocor Corp.; Phone Number: +1-617-880-7616; Email: info@sardocorcorp.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of DMD with confirmatory genetic testing
• Cardiomyopathy with left ventricular scar in at least 3 of 16 segments
• Left ventricular ejection fraction < 40%
• Individualized, optimized cardiac medical therapy and glucocorticoid treatment for at least 12 months prior to enrollment
• Willing and able to provide informed consent

Exclusion Criteria:

• Abnormal blood pressure
• Non-DMD-related liver function test elevations
• Cystatin C ≥ 1.2 mg/L
• Thrombocytopenia
• Anemia
• Inadequate pulmonary function

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose; SRD-001	Genetic: SRD-001; SRD-001 is an adeno-associated virus serotype 1 (AAV1) based gene therapy designed to deliver a copy of the gene encoding the human sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a). It is administered as a one-time intracoronary infusion.; Other Names: AAV1/SSERCA2a
Experimental: High Dose; SRD-001	Genetic: SRD-001; SRD-001 is an adeno-associated virus serotype 1 (AAV1) based gene therapy designed to deliver a copy of the gene encoding the human sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a). It is administered as a one-time intracoronary infusion.; Other Names: AAV1/SSERCA2a
No Intervention: Control; No-Intervention Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of all-cause mortality	Death	From Day 1 to Week 52 and Week 104
Rate and severity of related treatment-emergent adverse events	Adverse events related to the investigational product or the administration procedure	From Day 1 to Week 52 and Week 104
Rate and severity of all treatment-emergent adverse events	Adverse events	From Day 1 to Week 52 and Week 104
Rate of cell-mediated immune reaction	Cell-mediated immune reaction as assessed by enzyme-linked immunosorbent spot (ELISpot)	From Day 1 to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change, including normal/abnormal shifts, in 12-lead electrocardiogram (ECG)	Change in the heart's electrical activity	From Day 1 to Week 52 and Week 104
Change, including normal/abnormal shifts, in laboratory evaluations	Hematology, serum chemistries, urinalysis, cardiac enzymes and anti-AAV1 antibodies	From Day 1 to Week 52 and Week 104

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in myocardium and left ventricular structure and function	Assessed by cardiac magnetic resonance imaging with late gadolinium enhancement	From baseline to Week 52 and Week 104
Change in skeletal muscle function	Assessed by PUL 2.0, grip strength, key and tip-to-tip pinch strength and elbow flexion strength	From baseline to Week 52 and Week 104
Change in pulmonary function	Assessed by slow vital capacity, forced expiratory volume in 1 second, forced vital capacity, peak expiratory flow, maximum inspiratory pressure, maximum expiratory pressure, peak cough flow and inspiratory flow reserve	From baseline to Week 52 and Week 104
Change in quality of life	Assessed by the Duchenne muscular dystrophy quality of life questionnaire	From baseline to Week 52 and Week 104

Collaborators and Investigators

• Sponsor: Sardocor Corp.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: January 11, 2024
• First Submitted That Met QC Criteria: January 24, 2024
• First Posted (Estimated): January 25, 2024

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Cardiomegaly; Laminopathies; Muscular Dystrophies; Cardiomyopathies; Cardiomyopathy, Dilated; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: SRD-001-1004

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