Microdystrophin Gene Transfer Study in Adolescents and Children With DMD (IGNITE DMD)
Primary Purpose
Duchenne Muscular Dystrophy
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SGT-001
Sponsored by
About this trial
This is an interventional treatment trial for Duchenne Muscular Dystrophy
Eligibility Criteria
Inclusion Criteria:
- Established clinical diagnosis of DMD and documented dystrophin gene mutation predictive of DMD phenotype
- Confirmed absence of dystrophin as determined by muscle biopsy (ambulatory patients)
- Anti-AAV9 antibodies below protocol-specified thresholds
- Stable cardiac and pulmonary function
- Adolescents: non-ambulatory by protocol-specified criteria
- Children: ambulatory by protocol-specified criteria
- Stable daily dose (or equivalent) of oral corticosteroids ≥ 12 wks
Exclusion Criteria:
- Prior or ongoing medical condition or physical examination, ECG or laboratory findings that could adversely affect subject safety, compromise completion of treatment and follow-up, or impair assessment of study results
- Abnormal liver function
- Abnormal renal function
- Clinically significant coagulation abnormalities
- Impaired cardiovascular function based on cardiac MRI or ECHO
- Impaired respiratory function based on FVC % predicted or need for daytime ventilatory support
- Significant spinal deformity or presence of spinal rods
- Body mass index ≥ 95th percentile for age
- Exposure to another investigational drug within 3 months or 5 half-lives prior to screening
- Exposure to drugs affecting dystrophin or utrophin expression within 6 months prior to screening
Additional inclusion/exclusion criteria may apply. Patients over 30 kg will not be eligible for treatment at this time. A weight limit of ≤ 18 kg will be implemented for the next two patients to be dosed.
Sites / Locations
- David Geffen School of Medicine at UCLA
- University of Florida
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
No Intervention
Arm Label
SGT-001 - Dose Level 1
SGT-001 - Dose Level 2
Untreated Control
Arm Description
Single IV infusion of SGT-001 at starting dose
Single IV infusion of SGT-001 at next ascending dose
Untreated control group. After 1 year, treatment-eligible control patients will receive SGT-001 at the selected dose.
Outcomes
Primary Outcome Measures
Primary efficacy endpoint
Change from baseline in microdystrophin protein in muscle biopsies (active treatment group)
Primary safety endpoint
Incidence of adverse events
Primary safety endpoint
Incidence of clinical laboratory abnormalities
Primary safety endpoint
Incidence of abnormalities in vital signs
Primary safety endpoint
Incidence of abnormalities in physical examinations
Primary safety endpoint
Incidence of abnormalities on ECGs
Secondary Outcome Measures
Full Information
NCT ID
NCT03368742
First Posted
December 5, 2017
Last Updated
October 12, 2023
Sponsor
Solid Biosciences Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03368742
Brief Title
Microdystrophin Gene Transfer Study in Adolescents and Children With DMD
Acronym
IGNITE DMD
Official Title
A Randomized, Controlled, Open-label, Single-ascending Dose, Phase I/II Study to Investigate the Safety and Tolerability, and Efficacy of Intravenous SGT-001 in Male Adolescents and Children With Duchenne Muscular Dystrophy
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 6, 2017 (Actual)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
December 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Solid Biosciences Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a controlled, open-label, single-ascending dose study to evaluate the safety, tolerability and efficacy of SGT-001 in adolescents and children with Duchenne muscular dystrophy (DMD). Patients will receive a single intravenous (IV) infusion of SGT-001 and will be followed for approximately 5 years.
The protocol was amended to drop the control arm after 4 subjects were dosed. Subjects currently enrolling are assigned to active treatment. Control subjects enrolled under original protocol will continue through the study per the original protocol.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne Muscular Dystrophy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Active treatment group for all patients enrolled after June 2019. Total of approximately 16 to 32 patients.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
SGT-001 - Dose Level 1
Arm Type
Experimental
Arm Description
Single IV infusion of SGT-001 at starting dose
Arm Title
SGT-001 - Dose Level 2
Arm Type
Experimental
Arm Description
Single IV infusion of SGT-001 at next ascending dose
Arm Title
Untreated Control
Arm Type
No Intervention
Arm Description
Untreated control group. After 1 year, treatment-eligible control patients will receive SGT-001 at the selected dose.
Intervention Type
Genetic
Intervention Name(s)
SGT-001
Intervention Description
AAV9 vector containing muscle-specific promoter and microdystrophin construct
Primary Outcome Measure Information:
Title
Primary efficacy endpoint
Description
Change from baseline in microdystrophin protein in muscle biopsies (active treatment group)
Time Frame
12 months
Title
Primary safety endpoint
Description
Incidence of adverse events
Time Frame
12 months
Title
Primary safety endpoint
Description
Incidence of clinical laboratory abnormalities
Time Frame
12 months
Title
Primary safety endpoint
Description
Incidence of abnormalities in vital signs
Time Frame
12 months
Title
Primary safety endpoint
Description
Incidence of abnormalities in physical examinations
Time Frame
12 months
Title
Primary safety endpoint
Description
Incidence of abnormalities on ECGs
Time Frame
12 months
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Established clinical diagnosis of DMD and documented dystrophin gene mutation predictive of DMD phenotype
Confirmed absence of dystrophin as determined by muscle biopsy (ambulatory patients)
Anti-AAV9 antibodies below protocol-specified thresholds
Stable cardiac and pulmonary function
Adolescents: non-ambulatory by protocol-specified criteria
Children: ambulatory by protocol-specified criteria
Stable daily dose (or equivalent) of oral corticosteroids ≥ 12 wks
Exclusion Criteria:
Prior or ongoing medical condition or physical examination, ECG or laboratory findings that could adversely affect subject safety, compromise completion of treatment and follow-up, or impair assessment of study results
Abnormal liver function
Abnormal renal function
Clinically significant coagulation abnormalities
Impaired cardiovascular function based on cardiac MRI or ECHO
Impaired respiratory function based on FVC % predicted or need for daytime ventilatory support
Significant spinal deformity or presence of spinal rods
Body mass index ≥ 95th percentile for age
Exposure to another investigational drug within 3 months or 5 half-lives prior to screening
Exposure to drugs affecting dystrophin or utrophin expression within 6 months prior to screening
Additional inclusion/exclusion criteria may apply. Patients over 30 kg will not be eligible for treatment at this time. A weight limit of ≤ 18 kg will be implemented for the next two patients to be dosed.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roxana Donisa Dreghici, MD
Organizational Affiliation
Solid Biosciences
Official's Role
Study Director
Facility Information:
Facility Name
David Geffen School of Medicine at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Microdystrophin Gene Transfer Study in Adolescents and Children With DMD
We'll reach out to this number within 24 hrs