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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: November 22, 2016
Last verified: November 2016

February 23, 2012
November 22, 2016
February 2012
April 2016   (final data collection date for primary outcome measure)
  • Percent of dystrophin positive fibers [ Time Frame: Baseline to Week 20 ] [ 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 to Week 212 ] [ Designated as safety issue: No ]
    The primary functional efficacy endpoint will be the change from baseline to Week 212 on the 6 Minute Walk Test (6MWT).
The primary efficacy endpoint will be the change from baseline in the percent of dystrophin positive fibers in muscle biopsy tissue as measured by immunohistochemistry (IHC). [ Time Frame: 20 Weeks ] [ Designated as safety issue: Yes ]
The primary efficacy endpoint will be based on the pre-treatment and post-treament percent of dystrophin positive fibers as measured in the muscle biopsy tissue on(IHC).
Complete list of historical versions of study NCT01540409 on ClinicalTrials.gov Archive Site
Not Provided
The secondary efficacy endpoints will be the change from baseline in: CD3, CD4, and CD8 lymphocyte counts in muscle biopsy tissue; 6-Minute Walk Test (6-MWT) distance. [ Time Frame: 20,80 Weeks ] [ Designated as safety issue: Yes ]
A key secondary efficacy endpoint will be based on the pre-treatment and post-treatment CD3, CD4, and CD8 lymphocyte counts as measured in the muscle biopsy tissue as well as a 6-Minute Walk Test(6-MWT)distance.
  • Muscle Biopsy Tests [ Time Frame: Baseline to 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 to Week 212 ] [ Designated as safety issue: No ]
  • North Star Ambulatory Assessment (NSAA) results [ Time Frame: Baseline to Week 212 ] [ Designated as safety issue: No ]
  • Maximum voluntary isometric contraction test (MVICT) results [ Time Frame: Baseline to Week 212 ] [ Designated as safety issue: No ]
  • 9 Hole Peg Test results [ Time Frame: Baseline to Week 212 ] [ Designated as safety issue: No ]
  • Pediatric Quality of Life Inventory (PedsQL) results, including the neuromuscular module (NMM) [ Time Frame: Baseline to Week 212 ] [ Designated as safety issue: No ]
  • Pulmonary function test results [ Time Frame: Baseline to Week 212 ] [ 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).
Not Provided
 
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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Duchenne Muscular Dystrophy (DMD)
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 Name: EXONDYS 51
Experimental: AVI-4658 (Eteplirsen)
Multiple-Dose Extension Study
Intervention: Drug: AVI-4658 (Eteplirsen)
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
12
February 2017
April 2016   (final data collection date for primary outcome measure)

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.

Male
7 Years to 13 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01540409
4658-us-202
No
Not Provided
Not Provided
Sarepta Therapeutics
Sarepta Therapeutics
Not Provided
Principal Investigator: Jerry R Mendell, MD Nationwide Children's Hospital
Sarepta Therapeutics
November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP