Duchenne Muscular Dystrophy
Conditions
Keywords
DMD, Gene Therapy
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.
Interventions
GENETICSGT-003
Adeno-associated virus serotype SLB101 containing the human microdystrophin gene (h-µD5)
Sponsors
Solid Biosciences Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
0 Years to 17 Years
Healthy volunteers
No
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. * Negative for AAV antibodies. * Steroid regimen: * Cohorts 1, 2, 4, and 5: A stable daily oral steroid regimen of at least 0.5 mg/kg/day of prednisone or 0.75 mg/kg/day of deflazacort for ≥12 weeks prior to Screening Part A or Rescreening, allowing for weight-based modifications consistent with clinical practice. * Cohort 3: N/A * Meet 10-meter walk/run time criteria * Meet time to rise from supine criteria * Cohort 5: Meet Performance of Upper Limb (PUL) 2.0 criteria * Participant has body weight: ≤ 90 kg
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (AEs) | Day 360 | — |
| Change from baseline in Microdystrophin Protein Levels | Day 90 | Microdystrophin expression evaluation in muscle biopsies |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline of Microdystrophin Tissue Distribution by Immunofluorescence (IF) | Day 90, Day 360 | — |
| Change from baseline in Microdystrophin Protein Levels | Day 360 | Microdystrophin expression evaluation in muscle biopsies |
| Change from Baseline in Time to Rise Velocity | Day 360, Day 540 | The Time to rise from supine (TTR) (s) will be captured as part of item 12 of the North Star Ambulatory Assessment (NSAA). Assessment of muscle function using a 17-item scale with each item scored from 0 to 2 and a higher score meaning a better outcome. The NSAA total score is defined as the sum of all 17 items, ranging from 0 to 34, with a higher score meaning a better outcome. |
| Change from baseline in Stride Velocity 95th Centile (SV95C) | Day 360, Day 540 | Assessment of peak ambulatory performance captured by wearable activity monitoring device. |
| Change from baseline in 10-meter walk/run velocity | Day 360, Day 540 | The 10MWR (s) will be captured as part of item 17 of the NSAA. Assessment of muscle function using a 17-item scale with each item scored from 0 to 2 and a higher score meaning a better outcome. The NSAA total score is defined as the sum of all 17 items, ranging from 0 to 34, with a higher score meaning a better outcome. |
| 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 | Assessment of muscle function using a 17-item scale with each item scored from 0 to 2 and a higher score meaning a better outcome. The NSAA total score is defined as the sum of all 17 items, ranging from 0 to 34, with a higher score meaning a better outcome. |
| 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 | — |
Countries
Canada, Italy, United Kingdom, United States
Contacts
CONTACTSolid Bio Clinical Trials
STUDY_DIRECTORSolid Bio Clinical Trials
Solid Biosciences
Outcome results
None listed