Efficacy Study of AVI-4658 to Induce Dystrophin Expression in Selected Duchenne Muscular Dystrophy Patients

March 26, 2020 updated by: Sarepta Therapeutics, Inc.

A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Efficacy, Safety, Tolerability and Pharmacokinetics Study of AVI-4658(Eteplirsen),in the Treatment of Ambulant Subjects With Duchenne Muscular Dystrophy

This study is designed to assess the efficacy, safety, tolerability, and pharmacokinetics (PK) of AVI-4658 (eteplirsen) in both 50.0 mg/kg and 30.0 mg/kg doses administered over 24 weeks in subjects diagnosed with Duchenne muscular dystrophy (DMD).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

For details regarding the roll-over extension study 4658-us-202, please refer to NCT01540409.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

7 years to 13 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Major Inclusion and Exclusion Criteria:

Inclusion Criteria:

A subject must meet all of the following criteria to be eligible for this study.

  • Be a male with DMD and have an out-of-frame deletion(s) that may be corrected by skipping exon 51 [e.g., deletions of exons 45-50, 47-50, 48-50, 49-50, 50, 52, 52-63], as confirmed in a Clinical Laboratory Improvement Act-accredited laboratory by any of the peer-reviewed and published methodology that evaluates all exons (including, but not limited to, multiplex ligation-dependent probe, comparative genomic hybridization, and single condition amplification/internal primer analysis).
  • Be between the ages of 7 and 13 years, inclusive.
  • Have stable cardiac function and stable pulmonary function (forced vital capacity [FVC] ≥50% of predicted and not require supplemental oxygen) that, in the Investigator's opinion, is unlikely to decompensate over the duration of the study.
  • Be receiving treatment with oral corticosteroids and have been on a stable dose for at least 24 weeks before study entry. Subjects may be allowed to take other (non-RNA antisense or gene therapy) medication (including angiotensin-converting enzyme [ACE] inhibitors, β blockers, losartan potassium, and coenzyme Q) as long as they have been on a stable dose of the medication for 24 weeks before the screening visit (Visit 1) and the dose will remain constant throughout the study.
  • Have intact right and left biceps muscles or an alternative upper arm muscle group.
  • Achieve an average distance within 200m and 400m ±10% (i.e. within 180m and 440m) while walking independently over six minutes.
  • Have a left ventricular ejection fraction (LVEF) of >40% based on the ECHO that is obtained at the screening visit (Visit 1). A subject who has abnormal ECHO findings but who has an LVEF of >40% may be enrolled in the study at the Investigator's discretion; however, the subject must have been receiving stable doses of ACE inhibitors or β blockers for at least 24 weeks before study entry.
  • Have a parent(s) or legal guardian(s) who is able to understand and comply with the all of the study procedure requirements.
  • Be willing to provide informed assent and have a parent(s) or legal guardian(s) who is willing to provide written informed consent for the subject to participate in the study.

Exclusion Criteria:

A subject who meets any of the following criteria will be excluded from this study.

  • Use of any pharmacologic treatment, other than corticosteroids, that might have an effect on muscle strength or function within 12 weeks before study entry (e.g., growth hormone, anabolic steroids).
  • Previous treatment with the experimental agents eteplirsen, BMN-195, or PRO051.
  • Previous treatment with any other experimental agents or participation in any other DMD interventional clinical study within 12 weeks before entry into this study; including use of the shock training system or "STS," or planned use during this study.
  • Surgery within 3 months before study entry or planned surgery at any time during this study.
  • Presence of other clinically significant illness at the time of study entry, including significant renal dysfunction (as measured by urinary cystatin C, KIM-1, or urinary total protein), or average heart rate during screening Holter monitoring in excess of 110 bpm (unless subsequently treated and confirmed controlled and stable on a β-blocker) or QTc >450 ms.
  • Use of any aminoglycoside antibiotic within 12 weeks before the screening visit (Visit 1) or need for use of an aminoglycoside antibiotic during the study (unless discussed and agreed with the Principal Investigator and medical monitor).
  • Prior or ongoing medical condition that, in the Investigator's opinion, could adversely affect the safety of the subject or that makes it unlikely that the course of treatment or follow-up would be completed or could impair the assessment of study results.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AVI-4658 (Eteplirsen)
  1. 50 mg/kg eteplirsen for 28 weeks
  2. 30 mg/kg eteplirsen for 28 weeks
Drug: AVI-4658 (Eteplirsen)
Treatment group 1 (n=4): 50.0 mg/kg eteplirsen once weekly x 24 weeks via a 60-minute i.v. infusion Treatment group 2 (n=4): 30.0 mg/kg eteplirsen once weekly x 24 weeks via a 60-minute i.v. infusion Treatment group 3 (n=4): matching placebo once weekly x 24 weeks via a 60-minute i.v. infusion; treatment group 3a will match two placebo subjects to 50.0 mg/kg eteplirsen; treatment group 3b will match two placebo subjects to 30.0 mg/kg eteplirsen
Other Names:
  • Eteplirsen- Phosphorodiamidate Morphilino Oligomer
Placebo Comparator: Placebo / Delayed Treatment

3a. Placebo 50 mg/kg phosphate buffered saline solution identical in appearance to eteplirsen for 24 weeks followed by 50 mg/kg of eteplirsen for 4 weeks.

3b. Placebo 30 mg/kg phosphate buffered saline solution identical in appearance to eteplirsen for 24 weeks followed by 30 mg/kg of eteplirsen for 4 weeks.
Other: Placebo
sterile, isotonic, clear, colorless phosphate buffered saline solution of eteplirsen at a concentration of 100 mg/mL in single-use vials containing a nominal volume of 1.0 mL without preservatives.
Other Names:
  • Phosphate buffered saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the Number (%) of Dystrophin Positive Fibers
Time Frame: After 12 weeks for 4 patients who received 50 mg/kg and 2 patients who received placebo. After 24 weeks for 4 patients who received 30 mg/kg and 2 patients who received placebo.
The primary efficacy endpoint will be based on the pre-treatment and post-treatment change in the number (%) of dystrophin positive fibers as measured in the muscle biopsy tissue on immunohistochemistry (IHC).
After 12 weeks for 4 patients who received 50 mg/kg and 2 patients who received placebo. After 24 weeks for 4 patients who received 30 mg/kg and 2 patients who received placebo.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline: 6 Minute Walk Test (6MWT) - Intent to Treat Population (ITT)
Time Frame: 24 weeks
A key secondary efficacy endpoint will be based on the pre-treatment and post-treatment Change from baseline: 6 Minute Walk Test (6MWT) - Intent to Treat population (ITT)
24 weeks
Change From Baseline: 6 Minute Walk Test (6MWT) - Modified Intent to Treat Population (mITT)
Time Frame: 24 weeks
A key secondary efficacy endpoint will be based on the pre-treatment and post-treatment of the 6-MWT distance. Change from baseline: 6 Minute Walk Test (6MWT) - modified Intent-to-Treat population (mITT).
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sarepta Therapeutics, Inc.

Investigators

  • Study Director: Medical Director, Sarepta Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2011

Primary Completion (Actual)

February 1, 2012

Study Completion (Actual)

June 1, 2012

Study Registration Dates

First Submitted

July 8, 2011

First Submitted That Met QC Criteria

July 15, 2011

First Posted (Estimate)

July 18, 2011

Study Record Updates

Last Update Posted (Actual)

March 30, 2020

Last Update Submitted That Met QC Criteria

March 26, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4658-us-201
  • 07-2484 (Other Identifier: Office of Orphan Drug Development)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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