A study to investigate the safety, tolerability, and efficacy of SGT-001 in male adolescents and children with Duchenne muscular dystrophy

Phase 1

• Conditions: Duchenne muscular dystrophy; MedDRA version: 20.1 Level: PT Classification code 10052655 Term: Duchenne muscular dystrophy gene carrier System Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 20.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2017-002213-60-GB
• Lead Sponsor: Solid Biosciences Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-12-11
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 32

Inclusion Criteria

1. Male aged 4 years to 17 years, inclusive, at randomization;
2. Established clinical diagnosis of DMD and documented dystrophin gene mutation predictive of DMD phenotype:
o For children (aged 4 years to 11 years, inclusive), confirmed absence of dystrophin as determined by muscle biopsy IF
(= 10% dystrophin-positive fibers) or equivalent methodology, performed following randomization and prior to SGT-001 administration;
3. Anti-AAV9 total/circulating antibody titer <50,000 mU/mL, and anti-AAV9 neutralizing antibody titer =1:5;
4. Stable cardiac and pulmonary function;
5. For adolescents (aged 12 years to 17 years, inclusive) the following 2 criteria must be met:
o Unable to walk 10 meters without assistance, AND
o Score =4 on Brooke scale for upper extremity;
6. For children (aged 4 years to 11 years, inclusive) the following 2 criteria must be met:
o Walk and climb stairs with/without aid of railing (Vignos scale score
=3), AND
o Rise from the floor from supine (Gowers) time =7 seconds;
7. A stable dose of at least 0.5 mg/kg/day of oral daily prednisone or equivalent for at least 24 weeks prior to dosing and expected to remain constant throughout the study on a per kg basis, except for protocol-specified dose changes;
8. Use of medications frequently prescribed for subjects with DMD will be allowed provided the subject has been on a stable dose for 12 weeks prior to Screening and the dose remains constant throughout the study except for adjustments for weight;
9. Able to understand and comply with all study procedures and have a parent(s) or legal guardian(s) who is able to understand and comply with the study procedure requirements;
10. Be willing to provide informed assent and have a parent(s) or legal guardian(s) who is willing to provide written informed consent for the subject to participate in the study; and
11. Subjects of reproductive potential should utilize double barrier contraceptive methods during the duration of the study. These may include (but are not limited to) condom plus other highly effective contraceptive method (such as hormonal contraceptive or intrauterine device).
Are the trial subjects under 18? yes
Number of subjects for this age range: 16
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Any prior or ongoing medical condition, medical history, physical findings, ECG findings, or laboratory abnormality that, in the Investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results;
2. Abnormal liver function (gamma-glutamyl transferase >1.5 x upper limit of normal [ULN] or total bilirubin >ULN);
3. Abnormal renal function (cystatin C >1.2 x ULN);
4. Clinically significant abnormalities of coagulation including international normalized ratio (INR) or activated partial thromboplastin time (aPTT) >1.2 x ULN or platelets <125,000 cell/mm3;
5. Impaired cardiovascular function (shortening fraction <28%, EF <45% on cardiac MRI or ECHO, according to feasibility/age group);
6. Respiratory function predictive of (or requiring) the use of daytime ventilatory support, or
o FVC % predicted <60% (age 4-11 years);
o FVC % predicted <40%, and/or FVC <1 L (age = 12 years);
7. 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;
8. Significant spinal deformity and/or presence of spinal rods, which would interfere with positioning or imaging of the subject in the MRI scanner, including, but not limited to, severe scoliosis (ie, Cobb angle = 30 degrees);
9. Body mass index for age = 95th percentile;
10. For children (aged 4 years to 11 years, inclusive), loss of 30 degrees of plantar flexion from the normal range of movement at the ankle joint due to contracture;
11. A need, in the Investigator’s opinion, to undergo an invasive procedure (eg, spinal fusion or surgical contracture release) for 2 years after randomization;
12. Exposure to another investigational drug within 3 months prior to Screening or 5 half-lives since last administration, whichever is longer;
13. Exposure to approved or investigational drugs that may affect dystrophin or utrophin expression in the previous 6 months prior to Screening; or
14. Exposure to an approved or investigational gene transfer drug.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified