NCT01396239

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jul 2011

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2011

Completed
7 days until next milestone

First Submitted

Initial submission to the registry

July 8, 2011

Completed
10 days until next milestone

First Posted

Study publicly available on registry

July 18, 2011

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2012

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2012

Completed
3.4 years until next milestone

Results Posted

Study results publicly available

November 9, 2015

Completed
Last Updated

March 30, 2020

Status Verified

March 1, 2020

Enrollment Period

7 months

First QC Date

July 8, 2011

Results QC Date

July 2, 2013

Last Update Submit

March 26, 2020

Conditions

Duchenne Muscular Dystrophy

Keywords

DMD

Outcome Measures

Primary Outcomes (1)

  • Change in the Number (%) of Dystrophin Positive Fibers

    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 Outcomes (2)

  • 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)

    24 weeks

Study Arms (2)

AVI-4658 (Eteplirsen)

EXPERIMENTAL

1. 50 mg/kg eteplirsen for 28 weeks 2. 30 mg/kg eteplirsen for 28 weeks

Drug: AVI-4658 (Eteplirsen)

Placebo / Delayed Treatment

PLACEBO COMPARATOR

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

Interventions

AVI-4658 (Eteplirsen)DRUG

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

Also known as: Eteplirsen- Phosphorodiamidate Morphilino Oligomer
AVI-4658 (Eteplirsen)
PlaceboOTHER

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.

Also known as: Phosphate buffered saline
Placebo / Delayed Treatment

Eligibility Criteria

Age7 Years - 13 Years
Sexmale
Healthy VolunteersNo
Age GroupsChild (0-17)

You may not qualify if:

  • 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.
  • 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.
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (2)

  • 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.

    PMID: 26573217DERIVED

  • Mendell JR, Rodino-Klapac LR, Sahenk Z, Roush K, Bird L, Lowes LP, Alfano L, Gomez AM, Lewis S, Kota J, Malik V, Shontz K, Walker CM, Flanigan KM, Corridore M, Kean JR, Allen HD, Shilling C, Melia KR, Sazani P, Saoud JB, Kaye EM; Eteplirsen Study Group. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013 Nov;74(5):637-47. doi: 10.1002/ana.23982. Epub 2013 Sep 10.

    PMID: 23907995DERIVED

Related Links

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

eteplirsen

Condition Hierarchy (Ancestors)

Muscular DystrophiesMuscular Disorders, AtrophicMuscular DiseasesMusculoskeletal DiseasesNeuromuscular DiseasesNervous System DiseasesGenetic Diseases, X-LinkedGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

Due to the small number of study participants, a single adverse event (AE) in 1 patient exceeds the reporting threshold of 5%. Refer to the "Post-Hoc Outcome Measures" #4 and #5 for a summary of frequent and related AEs.

Results Point of Contact

Title
Edward M. Kaye MD, Interim CEO, SVP & Chief Medical Officer
Organization
Sarepta Therapeutics, Inc.
clinicaltrials@sarepta.com
+1-888-727-3782

Study Officials

  • Medical Director

    Sarepta Therapeutics, Inc.

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 8, 2011

First Posted

July 18, 2011

Study Start

July 1, 2011

Primary Completion

February 1, 2012

Study Completion

June 1, 2012

Last Updated

March 30, 2020

Results First Posted

November 9, 2015

Record last verified: 2020-03

Locations

US(1)