Clinical trial NCT03368742: Microdystrophin Gene Transfer Study in Adolescents and Children With 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Duchenne Muscular Dystrophy
Lead sponsor: Solid Biosciences Inc.
Sponsor class: INDUSTRY
First posted: 2017-12-11
Enrollment: 12
Sex: MALE
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a controlled, open-label, single-ascending dose study to evaluate the safety and tolerability of SGT-001 in adolescents and children with Duchenne muscular dystrophy (DMD). Participants 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 participants were dosed.


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 participants)
* 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 weeks

Exclusion Criteria:

* Prior or ongoing medical condition or physical examination, ECG or laboratory findings that could adversely affect participant 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.

Primary outcomes:
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Number of Participants with Clinically Significant Abnormalities in Laboratory Parameters
timeFrame: Up to 5 years
measure: Number of Participants with Clinically Significant Abnormalities in Vital Signs
timeFrame: Up to 5 years
measure: Number of Participants with Clinically Significant Abnormalities in Physical Examinations
timeFrame: Up to 5 years
measure: Number of Participants with Clinically Significant Abnormalities in Electrocardiogram (ECG)
timeFrame: Up to 5 years
measure: Change from Baseline in Microdystrophin Protein Levels in Muscle Biopsies Using Western Blot (WB)
timeFrame: Baseline, 12 months
measure: Change from Baseline in Microdystrophin Protein Levels in Muscle Biopsies Using Immunofluorescence (IF)
timeFrame: Baseline, 12 months
measure: Change from Baseline in North Star Ambulatory Assessment (NSAA) score in Ambulatory Participants
timeFrame: Baseline, 12 months
measure: Change from Baseline in 6-minute walk test (6MWT) Distance in Ambulatory Participants
timeFrame: Baseline, 12 months
measure: Change from Baseline in Total Upper Limb Function, as Measured by the Total Performance of the Upper Limb (PUL) Functional Scale Score
timeFrame: Baseline, 12 months
measure: Change from Baseline in Respiratory Function, as Measured by Forced Vital Capacity (FVC) % Predicted, Forced Expiratory Volume in 1 second (FEV1) % Predicted, and Peak Expiratory Flow (PEF) % Predicted
timeFrame: Baseline, 12 months
measure: Change from Baseline in Ejection Fraction, As Measured by Echocardiography
timeFrame: Baseline,12 months
measure: Change from Baseline in Left Ventricular End Systolic Volume, As Measured by Echocardiography
timeFrame: Baseline,12 months
measure: Change from Baseline in Myocardial Peak Circumferential Strain (Ecc), As Measured by Echocardiography
timeFrame: Baseline,12 months
measure: Change from Baseline in Quality of Life as Measured by the Paediatric Quality of Life Inventory (PedsQL) Duchenne muscular dystrophy (DMD) module and self-reported outcome measures as measured by the PODCI DMD module
timeFrame: Baseline, 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: Solid Biosciences
name: Solid Bio Clinical Trials
role: STUDY_DIRECTOR
References: