Duchenne Muscular Dystrophy (DMD)
Conditions
Keywords
DMD, Duchenne, Eteplirsen, dystrophy, dystrophin, exon 51
Brief summary
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.
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.
Interventions
Eteplirsen will be administered once weekly via an IV infusion. There are two treatment groups, 30 mg/kg and 50 mg/kg.
Sponsors
Sarepta Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
7 Years to 13 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the 6 Minute Walk Test (6MWT) at Week 240 | Parent Baseline and 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). |
| Change From Baseline in the Percentage of Dystrophin Positive Fibers (PDPF) at Week 48 | Parent Baseline and 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). |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 12 centers in the United States. Overall, 12 participants who completed parent study 4658-us-201 (NCT01396239) were enrolled between July 2011 and February 2012 in this extension study (4658-us-202; NCT01540409). A 4-week open label period (Week 24-28) was observed between the parent and extension study.
Pre-assignment details
Participants who received placebo in 4658-us-201 study were randomized in 1:1 ratio in this extension study to receive either eteplirsen 30 or 50 milligram per kilogram (mg/kg) and, those who received eteplirsen 30 or 50 mg/kg in 4658-us-201 received same treatment in this extension study.
Participants by arm
| Arm | Count |
|---|---|
| Eteplirsen 30 mg/kg Participants who received 30 mg/kg eteplirsen or placebo once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 30 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study. | 6 |
| Eteplirsen 50 mg/kg Participants who received 50 mg/kg eteplirsen or placebo once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 50 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Eteplirsen 30 mg/kg | Eteplirsen 50 mg/kg | Total |
|---|---|---|---|
| Age, Continuous | 9.2 years STANDARD_DEVIATION 0.75 | 8.8 years STANDARD_DEVIATION 1.47 | 9.0 years STANDARD_DEVIATION 1.13 |
| Region of Enrollment United States | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 4 / 6 | 2 / 6 |
Outcome results
Primary
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).
Time frame: Parent Baseline and Week 240
Population: The Intent-to-Treat Population (ITT) population included all participants randomized into parent study 4658-us-201. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. Results are reported below in 2 reporting groups based on evaluation period (Week 240) as applicable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eteplirsen 30 mg/kg | Change From Baseline in the 6 Minute Walk Test (6MWT) at Week 240 | -199.0 Meters | Standard Deviation 113.25 |
| Eteplirsen 50 mg/kg | Change From Baseline in the 6 Minute Walk Test (6MWT) at Week 240 | -258.0 Meters | Standard Deviation 175.65 |
Primary
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).
Time frame: Parent Baseline and Week 48
Population: The ITT population included all participants randomized into parent study 4658-us-201. Results are reported below in 3 reporting groups of placebo to eteplirsen, eteplirsen 30 mg/kg, and eteplirsen 50 mg/kg, respectively, based on evaluation period (Week 48) as applicable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eteplirsen 30 mg/kg | Change From Baseline in the Percentage of Dystrophin Positive Fibers (PDPF) at Week 48 | 37.70 Percentage of Dystrophin Positive Fibers | Standard Deviation 12.602 |
| Eteplirsen 50 mg/kg | Change From Baseline in the Percentage of Dystrophin Positive Fibers (PDPF) at Week 48 | 51.69 Percentage of Dystrophin Positive Fibers | Standard Deviation 7.089 |
| Eteplirsen 50 mg/kg | Change From Baseline in the Percentage of Dystrophin Positive Fibers (PDPF) at Week 48 | 42.93 Percentage of Dystrophin Positive Fibers | Standard Deviation 13.433 |