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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sarepta Therapeutics
ClinicalTrials.gov Identifier:
NCT01540409
First received: February 23, 2012
Last updated: October 14, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Duchenne Muscular Dystrophy (DMD)
Drug: AVI-4658 (Eteplirsen)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-Label, Multiple-Dose, Efficacy, Safety, and Tolerability Study of Eteplirsen in Subjects With Duchenne Muscular Dystrophy Who Participated in Study 4658-US-201

Resource links provided by NLM:


Further study details as provided by Sarepta Therapeutics:

Primary Outcome Measures:
  • Percent of dystrophin positive fibers [ Time Frame: 20 Weeks ] [ Designated as safety issue: No ]
    The primary biological efficacy endpoint will be the change from baseline at Week 20 in the percent of dystrophin positive fibers (type = anti-dystrophin antibody MANDYS106) in muscle biopsy tissue as measured by immunohistochemistry (IHC).

  • 6 Minute Walk Test (6MWT) [ Time Frame: Baseline, Wks 4, 8, 20, 32, 46, 56, 68, 92, 116, 140, 164 ] [ Designated as safety issue: No ]
    The primary functional efficacy endpoint will be the change from baseline to end-of-study on the 6 Minute Walk Test (6MWT).


Other Outcome Measures:
  • Muscle Biopsy [ Time Frame: Baseline, Week 20, Week 140 (optional) ] [ Designated as safety issue: No ]
    • Dystrophin intensity per fiber in muscle biopsy tissue as determined by IHC
    • CD3, CD4, and CD8 lymphocyte count in muscle biopsy tissue
    • Total dystrophin protein in muscle biopsy tissue as determined by Western blot analysis
    • Exon skipping in muscle biopsy tissue as assessed by reverse transcriptase polymerase chain reaction (RT PCR)

  • Timed 4 Step Test results [ Time Frame: Baseline, Wks 4, 8, 20, 32, 46, 56, 68, 92, 116, 140, 164 ] [ Designated as safety issue: No ]
  • North Star Ambulatory Assessment (NSAA) results [ Time Frame: Baseline, Wks 4, 8, 20, 32, 46, 56, 68, 92, 116, 140, 164 ] [ Designated as safety issue: No ]
  • Maximum voluntary isometric contraction test (MVICT) results [ Time Frame: Baseline, Wks 4, 8, 20, 32, 46, 56, 68, 92, 116, 140, 164 ] [ Designated as safety issue: No ]
  • 9 Hole Peg Test results [ Time Frame: Baseline, Wks 20, 46, 68, 92, 116, 140, 164 ] [ Designated as safety issue: No ]
  • Pediatric Quality of Life Inventory (PedsQL) results, including the neuromuscular module (NMM) [ Time Frame: Baseline, Wks 20, 46, 68, 116, 164 ] [ Designated as safety issue: No ]
  • Pulmonary function test results [ Time Frame: Baseline, Wks 8, 20, 32, 46, 68, 92, 116, 140, 164 ] [ Designated as safety issue: No ]
    including forced vital capacity (FVC), percent predicted FVC, forced expiratory volume in 1 second (FEV1), FEV1%, FEV1/FVC ratio, maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP)


Enrollment: 12
Study Start Date: February 2012
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AVI-4658 (Eteplirsen)
Multiple-Dose Extension Study
Drug: AVI-4658 (Eteplirsen)
Eteplirsen will be administered once weekly via an IV infusion. Their are two treatment groups, 30 mg/kg and 50 mg/kg.

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.

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.

  Eligibility

Ages Eligible for Study:   7 Years to 13 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01540409

Locations
United States, California
Miller Children's Hospital
Long Beach, California, United States, 90806
United States, Florida
University of Florida Clinical Research Center
Gainesville, Florida, United States, 32610
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington University Medical School
St. Louis, Missouri, United States, 63110
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Summerwood Pediatrics/Infusacare Medical Services
Liverpool, New York, United States, 13088
United States, North Carolina
Levine Children's Hospital
Charlotte, North Carolina, United States, 28203
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Virginia
Children's Specialty Group, Pediatric Neurology
Norfolk, Virginia, United States, 23510
United States, Wisconsin
Osceola Medical Center
Osceola, Wisconsin, United States, 54020
Sponsors and Collaborators
Sarepta Therapeutics
Investigators
Principal Investigator: Jerry R Mendell, MD Nationwide Children's Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Sarepta Therapeutics
ClinicalTrials.gov Identifier: NCT01540409     History of Changes
Other Study ID Numbers: 4658-us-202
Study First Received: February 23, 2012
Last Updated: October 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sarepta Therapeutics:
DMD, Duchenne, Eteplirsen, dystrophy, dystrophin, exon 51

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Muscular Diseases
Muscular Disorders, Atrophic
Musculoskeletal Diseases
Nervous System Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on October 23, 2014