Efficacy, Safety, and Tolerability Rollover Study of Eteplirsen in Subjects With Duchenne Muscular Dystrophy

Open-Label, Multiple-Dose, Efficacy, Safety, and Tolerability Study of Eteplirsen in Subjects With Duchenne Muscular Dystrophy Who Participated in Study 4658-US-201

The primary objective of this study is to assess the ongoing efficacy, safety, and tolerability of an additional 212 weeks of treatment with eteplirsen injection in Duchenne muscular dystrophy (DMD) subjects who have successfully completed the 28 week eteplirsen study: Study 4658-us-201. This study will also evaluate the correlation between biomarkers for DMD and the clinical status of participating DMD subjects.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy (DMD)
• Intervention / Treatment: Drug: AVI-4658 (Eteplirsen)

Detailed Description

This is an open label, multiple dose extension study to assess the ongoing efficacy, safety, and tolerability of weekly intravenous (IV) infusions of eteplirsen in DMD subjects who have successfully completed Study 4658-us 201.

Subjects will have the opportunity to enroll in this study during the last visit of Study 4658-us-201 (Week 28). Eligible subjects will receive once weekly IV infusions of eteplirsen (50 or 30 mg/kg) for an additional 212 weeks. Subjects will receive the same dose of eteplirsen they received in Study 4658-us-201. Subjects will thereafter continue to receive once weekly IV infusions of eteplirsen for up to an additional 72 week period (through week 284). If commercial eteplirsen becomes available during this additional 72 week period, participation in the study will be discontinued as subjects transition to commercial eteplirsen.

Safety, efficacy, pharmacokinetic (PK), and biomarker assessments will be performed at scheduled visits; adverse events (AEs) and concomitant medications and therapies will be continuously monitored.

If review of data from this open label study suggests that continued treatment with eteplirsen is warranted, this study may be extended by protocol amendment or subjects who successfully complete this study may have the opportunity to participate in a separate follow on, open label eteplirsen study.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Miller Children's Hospital
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Clinical Research Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University Medical School
  • New York
    • Liverpool, New York, United States, 13088
      • Summerwood Pediatrics/Infusacare Medical Services
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Levine Children's Hospital
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Children's Specialty Group, Pediatric Neurology
  • Wisconsin
    • Osceola, Wisconsin, United States, 54020
      • Osceola Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 13 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

A subject must meet all of the following criteria to be eligible for this study.

1. The subject and/or their parent/legal guardian are willing and able to provide signed informed consent.
2. The subject has successfully completed 28 weeks of treatment in Study 4658-US-201.
3. The subject has a parent(s) or legal guardian(s) who is able to understand and comply with all of the study procedure requirements.

Exclusion Criteria:

A subject who meets any of the following criteria will be excluded from this study.

1. The subject has a prior or ongoing medical condition that, in the Investigator's opinion, could adversely affect the safety of the subject or make it unlikely that the course of treatment or follow-up would be completed or impair the assessment of study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AVI-4658 (Eteplirsen); Multiple-Dose Extension Study	Drug: AVI-4658 (Eteplirsen); Eteplirsen will be administered once weekly via an IV infusion. There are two treatment groups, 30 mg/kg and 50 mg/kg.; Other Names: EXONDYS 51

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the 6 Minute Walk Test (6MWT) at Week 240	This study used a modified version of the 6MWT test procedure described in American Thoracic Society (ATS) 2002 guidelines, specifically adapted for patients with Duchenne muscular dystrophy. The participant was asked to walk a set course of 25 meters for 6 minutes (timed) and the distance walked in meters was recorded. Increases from baseline in 6MWT distance are indicative of improvement and decreases from baseline indicate worsening. Baseline here corresponds to the baseline in the parent study (4658-us-201, NCT01396239).	Parent Baseline and Week 240
Change From Baseline in the Percentage of Dystrophin Positive Fibers (PDPF) at Week 48	Dystrophin expression as assessed by percent dystrophin positive fibers was measured by immunohistochemistry (IHC) technique using primary anti-dystrophin antibody. Percent change from baseline is the arithmetic difference of the treatment time point minus baseline divided by baseline calculated for individual subjects. Baseline here corresponds to the baseline in the parent study (4658-us-201, NCT01396239).	Parent Baseline and Week 48

Collaborators and Investigators

• Sponsor: Sarepta Therapeutics, Inc.
• Investigators: Study Director: Medical Director, Sarepta Therapeutics, Inc.

Publications and helpful links

General Publications

• Mendell JR, Goemans N, Lowes LP, Alfano LN, Berry K, Shao J, Kaye EM, Mercuri E; Eteplirsen Study Group and Telethon Foundation DMD Italian Network. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016 Feb;79(2):257-71. doi: 10.1002/ana.24555. Epub 2016 Jan 8.

Helpful Links

• Mendell, 2013, Annals of Neurology
• Mendell, 2016, Annals of Neurology
• Kinane, 2018, Journal of Neuromuscular Diseases
• Charleston, 2018, Neurology

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2012
• Primary Completion (Actual): April 15, 2016
• Study Completion (Actual): August 16, 2017

Study Registration Dates

• First Submitted: February 23, 2012
• First Submitted That Met QC Criteria: February 27, 2012
• First Posted (Estimate): February 28, 2012

Study Record Updates

• Last Update Posted (Actual): March 30, 2020
• Last Update Submitted That Met QC Criteria: March 26, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: DMD, Duchenne, Eteplirsen, dystrophy, dystrophin, exon 51
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: 4658-us-202