Microdystrophin Gene Transfer Study in Adolescents and Children With DMD

Study Overview
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Brief Summary
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This is a controlled, open-label, single-ascending dose study to evaluate the safety, tolerability and efficacy of SGT-001 in adolescents and children with Duchenne muscular dystrophy (DMD). Patients will receive a single intravenous (IV) infusion of SGT-001 and will be followed for approximately 5 years. The protocol was amended to drop the control arm after 4 subjects were dosed. Subjects currently enrolling are assigned to active treatment. Control subjects enrolled under original protocol will continue through the study per the original protocol.

Official Title
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A Randomized, Controlled, Open-label, Single-ascending Dose, Phase I/II Study to Investigate the Safety and Tolerability, and Efficacy of Intravenous SGT-001 in Male Adolescents and Children With Duchenne Muscular Dystrophy

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Genetic: SGT-001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established clinical diagnosis of DMD and documented dystrophin gene mutation predictive of DMD phenotype Confirmed absence of dystrophin as determined by muscle biopsy (ambulatory patients) Anti-AAV9 antibodies below protocol-specified thresholds Stable cardiac and pulmonary function Adolescents: non-ambulatory by protocol-specified criteria Children: ambulatory by protocol-specified criteria Stable daily dose (or equivalent) of oral corticosteroids ≥ 12 wks Exclusion Criteria: Prior or ongoing medical condition or physical examination, ECG or laboratory findings that could adversely affect subject safety, compromise completion of treatment and follow-up, or impair assessment of study results Abnormal liver function Abnormal renal function Clinically significant coagulation abnormalities Impaired cardiovascular function based on cardiac MRI or ECHO Impaired respiratory function based on FVC % predicted or need for daytime ventilatory support Significant spinal deformity or presence of spinal rods Body mass index ≥ 95th percentile for age Exposure to another investigational drug within 3 months or 5 half-lives prior to screening Exposure to drugs affecting dystrophin or utrophin expression within 6 months prior to screening Additional inclusion/exclusion criteria may apply. Patients over 30 kg will not be eligible for treatment at this time. A weight limit of ≤ 18 kg will be implemented for the next two patients to be dosed.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Active treatment group for all patients enrolled after June 2019. Total of approximately 16 to 32 patients.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SGT-001 - Dose Level 1<br>Single IV infusion of SGT-001 at starting dose | Genetic: SGT-001<br>* AAV9 vector containing muscle-specific promoter and microdystrophin construct<br>|
| Experimental: SGT-001 - Dose Level 2<br>Single IV infusion of SGT-001 at next ascending dose | Genetic: SGT-001<br>* AAV9 vector containing muscle-specific promoter and microdystrophin construct<br>|
| No Intervention: Untreated Control<br>Untreated control group. After 1 year, treatment-eligible control patients will receive SGT-001 at the selected dose. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary efficacy endpoint | Change from baseline in microdystrophin protein in muscle biopsies (active treatment group) | 12 months | 
| Primary safety endpoint | Incidence of adverse events | 12 months | 
| Primary safety endpoint | Incidence of clinical laboratory abnormalities | 12 months | 
| Primary safety endpoint | Incidence of abnormalities in vital signs | 12 months | 
| Primary safety endpoint | Incidence of abnormalities in physical examinations | 12 months | 
| Primary safety endpoint | Incidence of abnormalities on ECGs | 12 months |