We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01396239
Recruitment Status : Completed
First Posted : July 18, 2011
Results First Posted : November 9, 2015
Last Update Posted : March 30, 2020
Sponsor:
Information provided by (Responsible Party):
Sarepta Therapeutics, Inc.

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Drug: AVI-4658 (Eteplirsen) Other: Placebo Phase 2

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : July 2011
Actual Primary Completion Date : February 2012
Actual Study Completion Date : June 2012


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 Name: 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 Name: Phosphate buffered saline




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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)

  2. 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   7 Years to 13 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01396239


Locations
Layout table for location information
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Sponsors and Collaborators
Sarepta Therapeutics, Inc.
Investigators
Layout table for investigator information
Study Director: Medical Director Sarepta Therapeutics, Inc.
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Sarepta Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01396239    
Other Study ID Numbers: 4658-us-201
07-2484 ( Other Identifier: Office of Orphan Drug Development )
First Posted: July 18, 2011    Key Record Dates
Results First Posted: November 9, 2015
Last Update Posted: March 30, 2020
Last Verified: March 2020
Keywords provided by Sarepta Therapeutics, Inc.:
DMD
Additional relevant MeSH terms:
Layout table for MeSH terms
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked