Dose-Titration and Open-label Extension Study of SRP-4045 in Advanced Stage Duchenne Muscular Dystrophy (DMD) Patients

Sarepta Therapeutics

Status and phase: Completed; Phase 1

Conditions: Duchenne Muscular Dystrophy

Treatments: Drug: SRP-4045; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02530905

4045-101

Details and patient eligibility

About

This is a first-in-human dose-titration and open-label extension study to assess safety, tolerability, and pharmacokinetics of SRP-4045 in advanced-stage Duchenne muscular dystrophy (DMD) patients with deletions amenable to exon 45 skipping.

Full description

This is a randomized, placebo-controlled dose-titration study to assess safety, tolerability, and pharmacokinetics of 4 dose levels of SRP-4045 in genotypically confirmed advanced-stage DMD patients with deletions amenable to exon 45 skipping.

After completion of the dose-titration portion of the study and SRP-4045 is determined to be safe, all patients will be evaluated on open-label SRP-4045 for the duration of the study.

Safety, including adverse event monitoring, routine laboratory assessments, and cardiac testing will be monitored through the duration of the dose-titration and open-label portions of the study.

Clinical efficacy will be assessed at regularly scheduled study visits via quality of life questionnaires and tests of pulmonary and upper extremity function through the duration of the dose-titration and open-label portions of the trial.

Enrollment: 12 patients

Sex: Male

Ages: 7 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Genotypically confirmed DMD (amenable to exon 45 skipping).
• Stable cardiac and pulmonary function.
• Limited or no ambulation.
• On a stable dose of oral corticosteroids for at least 24 weeks OR has not received corticosteroids for at least 24 weeks.

Exclusion criteria

• Current or previous treatment with the experimental agents SMT C1100 (BMN-195) or PRO045.
• Other experimental treatment in the past 12 weeks.
• If on cardiac medication, must be on a stable dose for the past 12 weeks.
• Major surgery within the past 3 months.

Other inclusion/exclusion criteria apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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12 participants in 3 patient groups, including a placebo group

Placebo (double-blind dose titration)

Placebo Comparator group

Description:

Participants with genotypically confirmed Duchenne muscular dystrophy (DMD) characterized by deletions amenable to exon 45 skipping will receive placebo-matching to casimersen intravenous (IV) infusions, once weekly over approximately 12 weeks in the double-blind period.

Treatment:

Drug: Placebo

SRP-4045 (double-blind dose titration)

Experimental group

Description:

Participants with genotypically confirmed DMD characterized by deletions amenable to exon 45 skipping will receive weekly IV infusions of casimersen at four escalating dose levels, each for at least 2 weeks: 4 milligrams per kilograms (mg/kg) during Week 1 to Week 2, followed by 10 mg/kg during Week 3 to Week 4, followed by 20 mg/kg during Week 5 to Week 6, followed by 30 mg/kg beginning at Week 7 and continue over approximately Week 12 in the double-blind period.

Treatment:

Drug: SRP-4045

SRP-4045 (open label extension period)

Experimental group

Description:

All participants who completed double blind period will be enrolled to receive casimersen 30 mg/kg once weekly, for up to Week 144 in the open label extension period.

Treatment:

Drug: SRP-4045