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

NCT ID: NCT02530905

Last Updated: 2021-05-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-08
• Study Completion Date: 2018-10-03

Brief Summary

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.

Detailed 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.

Conditions

Duchenne Muscular Dystrophy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo (double-blind dose titration)

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

SRP-4045 placebo-matching solution for IV infusion.

SRP-4045 (double-blind dose titration)

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.

Group Type: EXPERIMENTAL

SRP-4045

Intervention Type: DRUG

SRP-4045 solution for IV infusion.

SRP-4045 (open label extension period)

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.

Group Type: EXPERIMENTAL

SRP-4045

Intervention Type: DRUG

SRP-4045 solution for IV infusion.

Interventions

SRP-4045

SRP-4045 solution for IV infusion.

Intervention Type: DRUG

Placebo

SRP-4045 placebo-matching solution for IV infusion.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Sarepta Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Sarepta Therapeutics, Inc.

Locations

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Kennedy Krieger Institute

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

4045-101

Identifier Type: -

Identifier Source: org_study_id