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

Официальное название

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)

Обзор

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 12 центров

• 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
• … и ещё 4 центра

Канада · 1 центр

• The Hospital for Sick Children — Toronto

Италия · 1 центр

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Rome

Великобритания · 1 центр

• Great Ormond Street Hospital — London

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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