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

Phase 1
Recruiting
Conditions
Duchenne Muscular Dystrophy
Registration Number
NCT06138639
Lead Sponsor
Solid Biosciences Inc.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
Male
Target Recruitment
40
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 in exons 1 to 11 or 42 to 45, inclusive, in the DMD gene as documented by a genetic report and confirmed by Sponsor genetic testing.

Other inclusion or exclusion criteria apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Incidence of treatment-emergent adverse events (AEs)Day 360
Change from baseline in microdystrophin protein levelsDay 90

Microdystrophin expression evaluation in muscle biopsies

Secondary Outcome Measures
NameTimeMethod
Change from Baseline of Microdystrophin Tissue Distribution by Immunofluorescence (IF)Day 90, Day 360
Change from baseline in microdystrophin protein levelsDay 360

Microdystrophin expression evaluation in muscle biopsies

Change from Baseline in Time to Rise VelocityDay 360, Day 540
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 velocityDay 360, Day 540
Change from baseline in 4-stair climb velocityDay 360, Day 540
Change from baseline in North Star Ambulatory Assessment (NSAA) total scoreDay 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) distanceDay 360, Day 540
Number of Participants with Clinically Significant Abnormalities in Laboratory ParametersThrough Day 360 and Day 540
Number of Participants with Clinically Significant Abnormalities in Vital SignsThrough Day 360 and Day 540
Number of Participants with Clinically Significant Abnormalities in Physical ExaminationsThrough Day 360 and Day 540
Number of Participants with Clinically Significant Abnormalities in Electrocardiogram (ECG) or Echocardiography (ECHO)Through Day 360 and Day 540

Trial Locations

Locations (10)

Great Ormond Street Hospital

🇬🇧

London, United Kingdom

Arkansas Children's Hospital

🇺🇸

Little Rock, Arkansas, United States

University of California, Los Angeles Medical Center

🇺🇸

Los Angeles, California, United States

University of California, Davis

🇺🇸

Sacramento, California, United States

Rare Disease Research

🇺🇸

Atlanta, Georgia, United States

Washington University in St. Louis

🇺🇸

Saint Louis, Missouri, United States

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

Children's Hospital of the King's Daughters

🇺🇸

Norfolk, Virginia, United States

The Hospital for Sick Children

🇨🇦

Toronto, Ontario, Canada

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

🇮🇹

Rome, Italy

Great Ormond Street Hospital
🇬🇧London, United Kingdom
Lucinda Furtado
Contact
+44 (0)20 7762 6932
Lucinda.furtado@gosh.nhs.uk
Francesco Muntoni, MD
Principal Investigator

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