A Phase 1/2, Multicenter, Open-Label Study to Investigate the Safety, Tolerability, and Efficacy of a Single Intravenous Dose of SGT-003 in Males With Duchenne Muscular Dystrophy (INSPIRE DUCHENNE)
Overview
- Phase
- Phase 1
- Intervention
- SGT-003
- Conditions
- Duchenne Muscular Dystrophy
- Sponsor
- Solid Biosciences Inc.
- Enrollment
- 60
- Locations
- 30
- Primary Endpoint
- Incidence of treatment-emergent adverse events (AEs)
- Status
- Recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
This is a multicenter, open-label, non-randomized study to investigate the safety, tolerability, and efficacy of a single intravenous (IV) infusion of SGT-003 in participants with Duchenne muscular dystrophy. There will be 5 cohorts in this study. Cohort 1 will include participants 4 to < 7 years of age. Cohort 2 will include participants 7 to < 12 years of age. Cohort 3 will include participants 0 to < 4 years of age. Cohort 4 will include participants 12 to < 18 years of age. Cohort 5 will include participants 10 to < 18 years of age. Initiation of participant enrollment in Cohorts 4 and 5 will be subject to the accrual of safety and efficacy data from Cohorts 1-3. All participants will receive SGT-003 and will be enrolled in the study for 5 total years for long-term follow up.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Cohort 1: 4 to \<7 years of age
- •Cohort 2: 7 to \<12 years of age
- •Cohort 3: 0 to \< 4 years of age
- •Cohort 4: 12 to \< 18 years of age
- •Cohort 5: 10 to \< 18 years of age
- •Participant ambulatory status at the time of Screening Part A or Rescreening, as defined by the ability to complete a 10-meter walk/run test in \< 30 seconds:
- •Cohorts 1, 2, and 4: Ambulatory
- •Cohort 3: Either ambulatory or non-ambulatory
- •Cohort 5: Non-ambulatory, but having been previously ambulatory by history
- •Established clinical diagnosis of DMD and documented dystrophin gene mutation predictive of DMD phenotype confirmed by Sponsor genetic testing. In cases where a genotype may be predictive of residual dystrophin production and/or a clear clinical diagnosis of DMD cannot be made (e.g., due to age), evaluation of dystrophin levels in baseline muscle biopsies may be required to determine eligibility under this criterion.
Exclusion Criteria
- •Treatment with dystrophin modifying drugs within 3 months prior to screening.
- •Current or prior treatment with an approved or investigational gene transfer drug.
- •Exposure to certain approved or investigational drugs within 3 months prior to screening or 5 half-lives since last administration, whichever is longer.
- •Established clinical diagnosis of DMD that is associated with any deletion mutation invariant or variant predicted to not express exons 1 to 11 or, exons 42 to 45, or exons 57 to 69, inclusive, in the DMD gene as documented by a genetic report and confirmed by Sponsor genetic testing.
- •Other inclusion or exclusion criteria apply.
Arms & Interventions
Cohort 1: SGT-003
All ambulatory participants from age 4 to \< 7 years will receive a single IV infusion of SGT-003 on Day 1.
Intervention: SGT-003
Cohort 2: SGT-003
All ambulatory participants from age 7 to \< 12 years will receive a single IV infusion of SGT-003 on Day 1.
Intervention: SGT-003
Cohort 3: SGT-003
All participants from age 0 to \< 4 years will receive a single IV infusion of SGT-003 on Day 1.
Intervention: SGT-003
Cohort 4: SGT-003
All ambulatory participants from age 12 to \< 18 years will receive a single IV infusion of SGT-003 on Day 1.
Intervention: SGT-003
Cohort 5: SGT-003
All non-ambulatory participants from age 10 to \< 18 years will receive a single IV infusion of SGT-003 on Day 1.
Intervention: SGT-003
Outcomes
Primary Outcomes
Incidence of treatment-emergent adverse events (AEs)
Time Frame: Day 360
Change from baseline in Microdystrophin Protein Levels
Time Frame: Day 90
Microdystrophin expression evaluation in muscle biopsies
Secondary Outcomes
- Change from Baseline of Microdystrophin Tissue Distribution by Immunofluorescence (IF)(Day 90, Day 360)
- Change from baseline in Microdystrophin Protein Levels(Day 360)
- Change from Baseline in Time to Rise Velocity(Day 360, Day 540)
- Change from baseline in Stride Velocity 95th Centile (SV95C)(Day 360, Day 540)
- Change from baseline in 10-meter walk/run velocity(Day 360, Day 540)
- Change from baseline in 4-stair climb velocity(Day 360, Day 540)
- Change from baseline in North Star Ambulatory Assessment (NSAA) total score(Day 360, Day 540)
- Change from baseline in 6-minute walk test (6MWT) distance(Day 360, Day 540)
- Number of Participants with Clinically Significant Abnormalities in Laboratory Parameters(Through Day 360 and Day 540)
- Number of Participants with Clinically Significant Abnormalities in Vital Signs(Through Day 360 and Day 540)
- Number of Participants with Clinically Significant Abnormalities in Physical Examinations(Through Day 360 and Day 540)
- Number of Participants with Clinically Significant Abnormalities in Electrocardiogram (ECG) or Echocardiography (ECHO)(Through Day 360 and Day 540)