Phase 3 Randomized Double‑Blind Placebo‑Controlled Study of Single Intravenous SGT‑003 Gene Therapy in Ambulant Male Patients with Duchenne Muscular Dystrophy

The primary objective is to evaluate the efficacy of a single intravenous dose of SGT-003 compared with placebo by measuring change in muscle function in ambulant males with Duchenne muscular dystrophy.

Secondary objectives include:

• Assessment of changes in muscle function and strength.
• Quantification of microdystrophin expression in muscle biopsies.
• Evaluation of alterations in respiratory function.
• Measurement of changes in patient‑reported outcome measures.
• Characterization of the safety and tolerability profile of the investigational product.

Fifteen male participants aged 7 to less than 12 years with a confirmed diagnosis of Duchenne muscular dystrophy and a documented dystrophin gene mutation were enrolled. All subjects were ambulatory, defined as walking without assistive devices, and had a body weight of 50 kg or less. Eligibility required a stable daily oral glucocorticoid regimen (≥0.5 mg/kg/day prednisone or ≥0.75 mg/kg/day deflazacort) for at least six months, negative serology for adeno‑associated virus antibodies, and fulfillment of predefined 10‑meter walk/run and supine‑rise functional criteria. Participants were required to understand study procedures, with assent from the child and written informed consent from a parent or legal guardian. Individuals of reproductive potential and their partners agreed to use two highly effective contraceptive methods for 12 months after dosing. The cohort represents a vulnerable pediatric population selected on the basis of genetic confirmation, functional ability, and stable medication use.

The study is a Phase 3, multicenter, randomized, double‑blind, placebo‑controlled trial evaluating a single intravenous infusion of SGT‑003 versus normal saline in ambulant males aged 7 to <12 years with Duchenne muscular dystrophy. After obtaining assent and parental consent, participants undergo a screening visit to confirm eligibility criteria, including genetic diagnosis, steroid stability, body weight ≤50 kg, and negative AAV antibodies. Eligible subjects are randomized 1:1 to receive either the test product (100 × 10^12 viral particles in a suspension for IV infusion) or placebo, administered on Day 0. Follow‑up assessments are scheduled at regular intervals (e.g., Days 30, 90, 180, 270, 360, 450, and 540) to evaluate muscle function, microdystrophin expression, pulmonary function, and safety endpoints, with the primary efficacy endpoint measured as change from baseline in time‑to‑rise velocity at Day 540. The end‑of‑study visit occurs on Day 540, concluding approximately 18 months of participant involvement. Early termination may occur if a participant experiences a serious adverse event related to the investigational product, violates major protocol requirements, or withdraws consent at any time.

The investigational product, SGT-003, is supplied as a suspension for IV infusion and is administered as a single intravenous dose of 100 000 000 000 000 units (dose unit classified as “Other”). The infusion is delivered once per participant via a peripheral or central venous line, consistent with standard infusion practices.

The control arm receives placebo consisting of normal saline (0.9 % sodium chloride) for infusion. The saline solution is administered using the same infusion set and volume as the investigational product to maintain blinding.

Administration details include:

• Single‑dose regimen on Day 1 of the study.
• Infusion duration is defined by the study protocol to ensure comparable exposure time between active and control treatments.
• Compliance monitoring is performed by documenting infusion start and end times, infusion rate, and any interruptions in the case report form.
• All participants are observed for a predefined post‑infusion monitoring period to assess immediate safety parameters.

Efficacy will be evaluated by comparing the change from baseline to Day 540 in the primary endpoint, time to rise velocity, between participants receiving SGT‑003 and those receiving placebo. Secondary efficacy parameters include the change from baseline to Day 540 in stride velocity 95th centile measured by activity monitoring with the Syde wearable device, 10‑meter walk/run velocity, 4‑stair climb velocity, absolute North Star Ambulatory Assessment (NSAA) score, cumulative loss of function in NSAA items, % predicted forced vital capacity, % predicted peak expiratory flow, % predicted forced expiratory volume in 1 second, and the PODCI Global score. In addition, the change from baseline to Day 90 in microdystrophin protein levels and tissue distribution will be assessed.

Functional assessments (rise, walk/run, stair climb) and NSAA scoring will be performed using validated timed‑test protocols and the standardized NSAA questionnaire at baseline and at Day 540. Activity monitoring data will be collected continuously via the Syde wearable device, with the 95th centile stride velocity extracted at the Day 540 timepoint. Pulmonary function will be measured using standard spirometry to obtain % predicted FVC, PEF, and FEV1 at baseline and Day 540. Microdystrophin quantification will be performed on muscle biopsy samples using validated laboratory assays at baseline and Day 90. All efficacy data will be analyzed using appropriate statistical models to compare the treatment and placebo groups, adjusting for baseline values.