Efficacy, Safety, and Tolerability Rollover Study of Eteplirsen in Subjects With Duchenne Muscular Dystrophy
|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|
- 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).
- 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).
|Study Start Date:||February 2012|
|Estimated Study Completion Date:||February 2017|
|Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
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 Name: EXONDYS 51
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01540409
|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 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|
|Principal Investigator:||Jerry R Mendell, MD||Nationwide Children's Hospital|