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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01396239
• Date of registration: 08/07/2011
• Prospective Registration: No
• Primary sponsor: Sarepta Therapeutics, Inc.
• Public title: Efficacy Study of AVI-4658 to Induce Dystrophin Expression in Selected Duchenne Muscular Dystrophy Patients
• Scientific 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
• Date of first enrolment: July 2011
• Target sample size: 12
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01396239
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Medical Director
• Affiliation: Sarepta Therapeutics, Inc.

Key inclusion & exclusion 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, ß 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 ß 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
ß-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.



Age minimum: 7 Years
Age maximum: 13 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Duchenne Muscular Dystrophy

Intervention(s)

Drug: AVI-4658 (Eteplirsen)

Other: Placebo

Primary Outcome(s)

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.]

Secondary Outcome(s)

Change From Baseline: 6 Minute Walk Test (6MWT) - Modified Intent to Treat Population (mITT) [Time Frame: 24 weeks]

Change From Baseline: 6 Minute Walk Test (6MWT) - Intent to Treat Population (ITT) [Time Frame: 24 weeks]

Secondary ID(s)

4658-us-201

07-2484

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 09/11/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01396239