Clinical trial NCT06138639: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Duchenne Muscular Dystrophy
Keywords: DMD
Gene Therapy
Lead sponsor: Solid Biosciences Inc.
Sponsor class: INDUSTRY
First posted: 2023-11-18
Enrollment: 40
Sex: MALE
Minimum age (years): 0
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 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.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (AEs)
timeFrame: Day 360
measure: Change from baseline in microdystrophin protein levels
timeFrame: Day 90
Secondary outcomes:
measure: Change from Baseline of Microdystrophin Tissue Distribution by Immunofluorescence (IF)
timeFrame: Day 90, Day 360
measure: Change from baseline in microdystrophin protein levels
timeFrame: Day 360
measure: Change from Baseline in Time to Rise Velocity
timeFrame: Day 360, Day 540
measure: Change from baseline in stride velocity 95th centile (SV95C)
timeFrame: Day 360, Day 540
measure: Change from baseline in 10-meter walk/run velocity
timeFrame: Day 360, Day 540
measure: Change from baseline in 4-stair climb velocity
timeFrame: Day 360, Day 540
measure: Change from baseline in North Star Ambulatory Assessment (NSAA) total score
timeFrame: Day 360, Day 540
measure: Change from baseline in 6-minute walk test (6MWT) distance
timeFrame: Day 360, Day 540
measure: Number of Participants with Clinically Significant Abnormalities in Laboratory Parameters
timeFrame: Through Day 360 and Day 540
measure: Number of Participants with Clinically Significant Abnormalities in Vital Signs
timeFrame: Through Day 360 and Day 540
measure: Number of Participants with Clinically Significant Abnormalities in Physical Examinations
timeFrame: Through Day 360 and Day 540
measure: Number of Participants with Clinically Significant Abnormalities in Electrocardiogram (ECG) or Echocardiography (ECHO)
timeFrame: Through Day 360 and Day 540
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: University of California, Los Angeles Medical Center
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: Atlanta
country: United States
facility: Rare Disease Research
state: Georgia
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study officials:
affiliation: Solid Biosciences
name: Solid Bio Clinical Trials
role: STUDY_DIRECTOR
References: