Clinical trial NCT06224660: Modulation of SERCA2a of Intra-Myocytic Calcium Trafficking in Cardiomyopathy Secondary to Duchenne Muscular Dystrophy
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: DMD-Associated Dilated Cardiomyopathy
Lead sponsor: Sardocor Corp.
Sponsor class: INDUSTRY
First posted: 2024-01-25
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of all-cause mortality
timeFrame: From Day 1 to Week 52 and Week 104
measure: Rate and severity of related treatment-emergent adverse events
timeFrame: From Day 1 to Week 52 and Week 104
measure: Rate and severity of all treatment-emergent adverse events
timeFrame: From Day 1 to Week 52 and Week 104
measure: Rate of cell-mediated immune reaction
timeFrame: From Day 1 to Week 52
Secondary outcomes:
measure: Change, including normal/abnormal shifts, in 12-lead electrocardiogram (ECG)
timeFrame: From Day 1 to Week 52 and Week 104
measure: Change, including normal/abnormal shifts, in laboratory evaluations
timeFrame: From Day 1 to Week 52 and Week 104
Other outcomes:
measure: Change in myocardium and left ventricular structure and function
timeFrame: From baseline to Week 52 and Week 104
measure: Change in skeletal muscle function
timeFrame: From baseline to Week 52 and Week 104
measure: Change in pulmonary function
timeFrame: From baseline to Week 52 and Week 104
measure: Change in quality of life
timeFrame: From baseline to Week 52 and Week 104
Locations:
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
Study officials:
References: