Phase 1/2 Multicenter Open-Label Study on Safety and Efficacy of SGT-003 Gene Therapy in Ambulant Males with Duchenne Muscular Dystrophy
- Trial ID
- 2024-514501-57-00
- Protocol
- SGT-003-101
- Sponsor
- Solid Biosciences Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to investigate the **safety** and **tolerability** of a single intravenous dose of SGT-003 in ambulant males with **Duchenne muscular dystrophy**. This is clinically relevant as it aims to ensure that the gene therapy is safe for use in patients, which is a critical step before considering its broader application.
Secondary objectives include:
- To assess the efficacy of SGT-003 by evaluating **microdystrophin expression** in muscle biopsies.
- To evaluate changes in **muscle function** and strength following administration.
- To assess changes in **pulmonary function** as a measure of efficacy.
- To further investigate the safety and tolerability of SGT-003.
- To evaluate the safety profile by assessing **pharmacokinetics**, shedding, and **immunogenicity**.
Participants
The clinical trial investigating the safety and tolerability of a single intravenous dose of SGT-003 for **Duchenne muscular dystrophy** includes a total of 38 male participants. The study population is divided into two cohorts based on age: Cohort 1 consists of participants aged 4 to less than 7 years, and Cohort 2 includes those aged 7 to less than 12 years. All participants are required to be ambulatory, defined as being able to walk without the use of an assistive device, and must have an established clinical diagnosis of Duchenne muscular dystrophy with a documented dystrophin gene mutation predictive of the disease phenotype. Participants are also required to be on a stable dose of oral daily prednisone or deflazacort for at least 12 weeks prior to entering the study. The trial population was selected based on these criteria, ensuring that participants are able to understand and comply with study procedures, with the assistance of a parent or legal guardian. The study does not include female subjects, and participants must weigh 50 kg or less. Additionally, participants must test negative for AAV antibodies and meet specific physical performance criteria, such as the 10-meter walk/run time and time to rise from supine. The trial focuses on a vulnerable population, given the age and health condition of the participants.
Plans and Procedures
The clinical trial is a **Phase 1/2** study designed to evaluate the safety, tolerability, and efficacy of a single intravenous dose of **SGT-003** in ambulant males with **Duchenne muscular dystrophy**. The trial employs an open-label design, meaning that both the researchers and participants are aware of the treatment being administered. The study is expected to commence recruitment on January 2, 2025, and conclude by July 3, 2030. Participants will be involved in the study for a duration that includes multiple visits, starting with an inclusion (screening) visit, followed by regular follow-up visits, and concluding with an end-of-study visit.
The inclusion visit will assess eligibility based on criteria such as age, ambulatory status, and genetic confirmation of **Duchenne muscular dystrophy**. Participants must be male, aged between 4 to less than 12 years, and ambulatory without assistive devices. They must also have a stable dose of corticosteroids and meet specific physical performance criteria. The follow-up visits will monitor the incidence of treatment-emergent adverse events, changes in microdystrophin protein levels, and various functional assessments, including the North Star Ambulatory Assessment and 6-minute walk test. The end-of-study visit will finalize data collection and assess long-term safety and efficacy outcomes.
Participant involvement is expected to last up to 360 days, with conditions for early termination including the occurrence of significant adverse events or withdrawal of consent. The primary endpoint focuses on the incidence of treatment-emergent adverse events, while secondary endpoints include changes in microdystrophin levels and various functional and respiratory assessments. The study will also characterize viral shedding, vector kinetics, and immunological responses associated with **SGT-003**. The trial is not classified as low intervention, reflecting its comprehensive evaluation of a novel gene therapy approach.
Treatment
The clinical trial involves the administration of **SGT-003**, an experimental gene therapy product developed by Solid Biosciences, LLC. **SGT-003** is formulated as a **suspension for intravenous infusion** and is designed for a single administration. The active substance in **SGT-003** is a structurally diverse substance, specifically a gene therapy vector utilizing an adeno-associated virus to deliver the human microdystrophin gene. The route of administration is **intravenous**, and the study is focused on evaluating the safety, tolerability, and efficacy of this single-dose treatment in ambulant males with Duchenne Muscular Dystrophy.
In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is open-label, meaning that both the researchers and participants are aware of the treatment being administered. The study does not include a pediatric formulation, and **SGT-003** is not classified as an orphan drug. Participant compliance with the treatment protocol is monitored through standard clinical trial procedures, ensuring adherence to the dosing schedule and accurate assessment of the treatment's effects.
Efficacy
Efficacy in this clinical trial will be assessed using a range of secondary endpoints. These include changes from baseline in **microdystrophin** protein levels and tissue distribution, as well as functional assessments such as the North Star Ambulatory Assessment (NSAA) score, 6-minute walk test (6MWT) distance, stride velocity 95th centile (SV95C), 10-meter walk/run velocity, 4-stair climb velocity, and time to rise velocity. Additionally, respiratory function will be evaluated through changes in % predicted forced vital capacity (FVC), % predicted peak expiratory flow (PEF), and % predicted forced expiratory volume in 1 second (FEV1).
Further assessments will include the incidence of clinical laboratory abnormalities, abnormalities in vital signs, physical examinations, and cardiac abnormalities as determined by electrocardiogram (ECG) or echocardiography (ECHO). The study will also characterize viral shedding, vector kinetics, and biodistribution in blood and muscle, as well as SGT-003 associated immunological responses through antibody testing and enzyme-linked immunospot (ELISpot). These parameters will be measured and analyzed at various timepoints throughout the study to determine the efficacy of the investigational product, SGT-003, in treating Duchenne Muscular Dystrophy.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant age at the time of signing the informed consent form (ICF): Cohort 1: 4 to <7 years Cohort 2: 7 to <12 years Cohort 3: 0 to < 4 years Cohort 4: 12 to < 18 years Cohort 5: 10 to < 18 years
- 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: a. 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. b. 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.
- Participant is male.
- Able to understand and comply with all study procedures as appropriate by age and have a parent(s) or legal guardian(s) (i.e., legally authorized representative [LAR]) who is (are) able to understand and comply with the study procedure requirements
- If participant is of reproductive potential, participant and partner of childbearing potential are willing to use 2 highly effective forms of contraception for 12 months following study drug administration.
Exclusion Criteria
- Any prior or ongoing medical condition, medical history, physical finding that in the Investigator's opinion could adversely affect the safety of the participant, make it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
- Abnormal liver function, evidence of active viral hepatitis
- Abnormal renal function
- Clinically significant abnormalities of coagulation
- Impaired cardiovascular function
- Pulmonary function predictive of (or requiring) the use of daytime ventilatory support
- Have severe hypersensitivity reactions, including anaphylaxis, to SGT-003 or its components.
- 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.
- Major surgery within 3 months prior to recruitment or planned orthopedic surgery for any time during this study which would interfere with the ability to perform outcome measures.
- Established clinical diagnosis of DMD that is associated with any deletion variant or variant predicted to not express exons 1 to 11, 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.
- Sponsor employees and their family members are ineligible to participate in this study.
- Any active infection
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Recruiting | 02 Jan 2025 | 8 |