Microdystrophin Gene Transfer Study in Adolescents and Children With DMD (IGNITE DMD)

• ClinicalTrials.gov Identifier: NCT03368742
• Recruitment Status: Active, not recruiting
• First Posted: December 11, 2017
• Last Update Posted: April 13, 2023
• Sponsor: Solid Biosciences Inc.
• Information provided by (Responsible Party): Solid Biosciences Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Duchenne Muscular Dystrophy	Genetic: SGT-001	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: Active treatment group for all patients enrolled after June 2019. Total of approximately 16 to 32 patients.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 6, 2017
• Estimated Primary Completion Date: December 2026
• Estimated Study Completion Date: December 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Primary efficacy endpoint [ Time Frame: 12 months ]
   Change from baseline in microdystrophin protein in muscle biopsies (active treatment group)
2. Primary safety endpoint [ Time Frame: 12 months ]
   Incidence of adverse events
3. Primary safety endpoint [ Time Frame: 12 months ]
   Incidence of clinical laboratory abnormalities
4. Primary safety endpoint [ Time Frame: 12 months ]
   Incidence of abnormalities in vital signs
5. Primary safety endpoint [ Time Frame: 12 months ]
   Incidence of abnormalities in physical examinations
6. Primary safety endpoint [ Time Frame: 12 months ]
   Incidence of abnormalities on ECGs

Eligibility Criteria

• Ages Eligible for Study: 4 Years to 17 Years (Child)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

David Geffen School of Medicine at UCLA

Los Angeles, California, United States, 90095

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610

Sponsors and Collaborators

Solid Biosciences Inc.

Investigators

• Study Director: Roxana Donisa Dreghici, MD; Solid Biosciences

More Information

• Responsible Party: Solid Biosciences Inc.
• ClinicalTrials.gov Identifier: NCT03368742
• Other Study ID Numbers: GX1001
• First Posted: December 11, 2017
• Last Update Posted: April 13, 2023
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked