Duchenne Muscular Dystrophy (DMD)Phase 2NCT01540409
Efficacy, Safety, and Tolerability Rollover Study of Eteplirsen in Subjects With Duchenne Muscular Dystrophy
A Phase 2 study testing AVI-4658 (Eteplirsen) in people with Duchenne Muscular Dystrophy (DMD), run by Sarepta Therapeutics, Inc. at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 to 13 years, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy (DMD)
- What is being tested?
- AVI-4658 (Eteplirsen)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 11 sitesUnited States
- Study dates
- 27 Feb 2012to 16 Aug 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 13 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- A subject must meet all of the following criteria to be eligible for this study.
- The subject and/or their parent/legal guardian are willing and able to provide signed informed consent.
- The subject has successfully completed 28 weeks of treatment in Study 4658-US-201.
- The subject has a parent(s) or legal guardian(s) who is able to understand and comply with all of the study procedure requirements.
Who cannot join
- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Levine Children's Hospital
Charlotte, North Carolina, 28203
Rush University Medical Center
Chicago, Illinois, 60612
Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Florida Clinical Research Center
Gainesville, Florida, 32610
Summerwood Pediatrics/Infusacare Medical Services
Liverpool, New York, 13088
Miller Children's Hospital
Long Beach, California, 90806
Children's Specialty Group, Pediatric Neurology
Norfolk, Virginia, 23510
Osceola Medical Center
Osceola, Wisconsin, 54020
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Washington University Medical School
St Louis, Missouri, 63110
About this study
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
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.
Read the 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.
- Conditions
- Duchenne Muscular Dystrophy (DMD)
- Being tested
- AVI-4658 (Eteplirsen)
- Keywords
- DMD, Duchenne, Eteplirsen, dystrophy, dystrophin, exon 51
- Medical subject headings
- Muscular Dystrophy, Duchenne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AVI-4658 (Eteplirsen)Drug
Also called EXONDYS 51
Eteplirsen will be administered once weekly via an IV infusion. There are two treatment groups, 30 mg/kg and 50 mg/kg.
| Study group | Role | What they receive |
|---|---|---|
| AVI-4658 (Eteplirsen) | Experimental | Multiple-Dose Extension Study Receives: Drug: AVI-4658 (Eteplirsen) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: Parent Baseline and Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2012 (estimated)
- Study start27 Feb 2012
- Primary completion15 Apr 2016
- Study completion16 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Duchenne Muscular Dystrophy (DMD)Studies of the same condition, open and under way.
- More trials run by Sarepta Therapeutics, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sarepta Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Sarepta Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01540409
- Sponsor's protocol ID
- 4658-us-202
- Status last verified
- Mar 2020
- First submitted
- 23 Feb 2012
- Last updated
- 30 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 26573217
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01540409
- Acronym / sponsor ID
- 4658-us-202
- Conditions
- Duchenne Muscular Dystrophy (DMD)
- Keywords
- DMD, Duchenne, Eteplirsen, dystrophy, dystrophin, exon 51
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Sarepta Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 27 Feb 2012 (actual)
- Primary completion
- 15 Apr 2016 (actual)
- Study completion
- 16 Aug 2017 (actual)
- First posted
- 28 Feb 2012 (estimated)
- Results
- Posted 10 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AVI-4658 (Eteplirsen) | Experimental | Drug: AVI-4658 (Eteplirsen)Multiple-Dose Extension Study |
Who may qualify
- Ages
- 7 to 13 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- A subject must meet all of the following criteria to be eligible for this study.
- The subject and/or their parent/legal guardian are willing and able to provide signed informed consent.
- The subject has successfully completed 28 weeks of treatment in Study 4658-US-201.
- The subject has a parent(s) or legal guardian(s) who is able to understand and comply with all of the study procedure requirements.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AVI-4658 (Eteplirsen)Also: EXONDYS 51Eteplirsen will be administered once weekly via an IV infusion. There are two treatment groups, 30 mg/kg and 50 mg/kg. | Drug | AVI-4658 (Eteplirsen) |
Primary outcome
Change From Baseline in the 6 Minute Walk Test (6MWT) at Week 240
Time frame: 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
Time frame: 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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26573217Mendell 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.
- Mendell, 2013, Annals of NeurologyLink provided by the sponsor.
- Mendell, 2016, Annals of NeurologyLink provided by the sponsor.
- Kinane, 2018, Journal of Neuromuscular DiseasesLink provided by the sponsor.
- Charleston, 2018, NeurologyLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Sarepta Therapeutics, Inc.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AVI-4658 (Eteplirsen) in people with Duchenne Muscular Dystrophy (DMD), run by Sarepta Therapeutics, Inc. at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in the 6 Minute Walk Test (6MWT) at Week 240 (time frame: Parent Baseline and Week 240). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01540409, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2020.