A Study of SGT-003 Gene Therapy in Duchenne Muscular Dystrophy (INSPIRE DUCHENNE)

Official title

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

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

• Genetic SGT-003
  Adeno-associated virus serotype SLB101 containing the human microdystrophin gene (h-µD5)

Primary outcome measures

• Incidence of treatment-emergent adverse events (AEs) [Time frame: Day 360]
• Change from baseline in Microdystrophin Protein Levels [Time frame: Day 90]

Secondary outcome measures (12)

• Change from Baseline of Microdystrophin Tissue Distribution by Immunofluorescence (IF) [Time frame: Day 90, Day 360]
• Change from baseline in Microdystrophin Protein Levels [Time frame: Day 360]
• Change from Baseline in Time to Rise Velocity [Time frame: Day 360, Day 540]
• Change from baseline in Stride Velocity 95th Centile (SV95C) [Time frame: Day 360, Day 540]
• Change from baseline in 10-meter walk/run velocity [Time frame: Day 360, Day 540]
• Change from baseline in 4-stair climb velocity [Time frame: Day 360, Day 540]
• Change from baseline in North Star Ambulatory Assessment (NSAA) total score [Time frame: Day 360, Day 540]
• Change from baseline in 6-minute walk test (6MWT) distance [Time frame: Day 360, Day 540]
• Number of Participants with Clinically Significant Abnormalities in Laboratory Parameters [Time frame: Through Day 360 and Day 540]
• Number of Participants with Clinically Significant Abnormalities in Vital Signs [Time frame: Through Day 360 and Day 540]
• Number of Participants with Clinically Significant Abnormalities in Physical Examinations [Time frame: Through Day 360 and Day 540]
• Number of Participants with Clinically Significant Abnormalities in Electrocardiogram (ECG) or Echocardiography (ECHO) [Time frame: Through Day 360 and Day 540]

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.
• 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 exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 12 centers

• Arkansas Children's Hospital — Little Rock
• University of California, Los Angeles Medical Center — Los Angeles
• University of California, Davis — Sacramento
• University of California — San Diego
• Rare Disease Research — Atlanta
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago
• Washington University in St. Louis — St Louis
• Nationwide Children's Hospital — Columbus
• … and 4 more centers

Canada · 1 center

• The Hospital for Sick Children — Toronto

Italy · 1 center

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Rome

United Kingdom · 1 center

• Great Ormond Street Hospital — London

Identifiers

NCT: NCT06138639 · SGT-003-101 · 2024-514501-57-00 · 1010251

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗