Phase I/II Study of SRP-4053 in DMD Patients

Sarepta Therapeutics

Status and phase: Completed; Phase 2; Phase 1

Conditions: Duchenne Muscular Dystrophy

Treatments: Drug: SRP-4053; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02310906

4053-101

Details and patient eligibility

About

This is a first-in-human, multiple-dose 2-part study to assess the safety, tolerability, efficacy, and pharmacokinetics of SRP-4053 in Duchenne muscular dystrophy (DMD) patients with deletions amenable to exon 53 skipping.

Full description

Part 1: Randomized, placebo-controlled dose-titration to assess safety, tolerability and pharmacokinetics of 4 dose levels of SRP-4053 in genotypically-confirmed DMD patients with deletions amenable to exon 53 skipping.

Part 2: Open-label evaluation of SRP-4053 in patients from Part 1, along with newly enrolled DMD patients with deletions amenable to exon 53 skipping and an untreated group of DMD patients with deletions not amenable to exon 53 skipping.

Safety, including adverse event monitoring and routine laboratory assessments, will be followed on an ongoing basis for all patients.

Clinical efficacy, including functional tests such as the six-minute walk test (6MWT), will be assessed at regularly scheduled study visits. Patients in the treated groups will undergo one baseline and one follow-up muscle biopsy. Patients in the untreated group will not undergo biopsies and will follow an abbreviated schedule of study assessments.

Enrollment: 39 patients

Sex: Male

Ages: 6 to 15 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosed with DMD, genotypically confirmed.
• Intact right and left biceps muscles or an alternative upper arm muscle group.
• Stable pulmonary and cardiac function.
• Minimum performance on 6MWT, North Star Ambulatory Assessment, and rise (Gowers) test as specified in the study protocol.
• On a stable dose of corticosteroids for at least 6 months.

Exclusion criteria

• Previous treatment with the experimental agents BMN-195 (SMT C1100) or PRO053.
• Current or previous treatment with any other experimental treatments within 12 weeks prior to study entry.
• Major surgery within the last 3 months.
• Presence of other clinically significant illness.
• Major change in physical therapy regime within the last 3 months.

Other inclusion and exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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39 participants in 4 patient groups, including a placebo group

Part 1: SRP-4053

Experimental group

Description:

Patients will receive SRP-4053 (golodirsen) intravenous (IV) infusions, weekly, at escalating dose levels as follows: Weeks 1-2, 4 mg/kg/week; Weeks 3-4, 10 mg/kg/week; Weeks 5-6, 20 mg/kg/week; Weeks 7-12, 30 mg/kg/week. Dosing will be interrupted or halted if specific predefined stopping criteria are met or if warranted at the discretion of the Sponsor or Investigator.

Treatment:

Drug: SRP-4053

Part 1: Placebo

Placebo Comparator group

Description:

Patients will receive SRP-4053 placebo-matching IV infusions, weekly, for 12 weeks. Dosing will be interrupted or halted if specific predefined stopping criteria are met or if warranted at the discretion of the Sponsor or Investigator.

Treatment:

Drug: Placebo

Part 2: SRP-4053

Experimental group

Description:

All eligible patients from Part 1, as well as new patients, will receive SRP-4053 (golodirsen) 30 mg/kg/week IV infusions, weekly, for up to 168 weeks.

Treatment:

Drug: SRP-4053

Part 2: Untreated Group

No Intervention group

Description:

Patients with DMD who have a genotypically confirmed deletion of exon(s) not amenable to treatment by exon 53 skipping, but who otherwise meet the same eligibility criteria as treated patients newly recruited to Part 2, will undergo the same study assessments as treated Patients (except for pharmacokinetic \[PK\] sampling and muscle biopsies), but at a reduced schedule through Week 144. The untreated patients are not considered as control group.