A Double-Blind, Placebo-Controlled, Multicenter Study With an Open-Label Extension to Evaluate the Efficacy and Safety of SRP-4045 and SRP-4053 in Patients With Duchenne Muscular Dystrophy
- Conditions
- 10028396Duchenne muscular dystrophymuscle disorder
- Registration Number
- NL-OMON42902
- Lead Sponsor
- Sarepta Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 4
1. Is a male with an established clinical diagnosis of DMD and an out-of-frame deletion amenable to:
* Exon 45 skipping (including but not limited to deletions of exons such as 12-44, 18-44, 44, 46-47, 46-48, 46-49, 46-51, 46-53, or 46-55) OR
* Exon 53 skipping (including but not limited to deletions of exons such as 42-52, 45-52, 47-52, 48-52,49-52, 50-52, 52, or 54-58) as documented by a genetic report from an accredited laboratory confirming deletion endpoints by multiplex ligation-dependent probe amplification or sequencing.
2. Is 7 to 13 years of age, inclusive.
3. Has stable pulmonary function (forced vital capacity % of predicted [FVC%] *50% and no requirement for nocturnal ventilation) that, in the Investigator*s opinion, is unlikely to decompensate over the duration of the study.
4. Has intact right and left biceps muscles (the preferred biopsy site) or 2 alternative upper arm muscle groups.
5. Has been on a stable dose or dose equivalent of oral corticosteroids for at least 24 weeks prior to Week 1 and the dose is expected to remain constant (except for modifications to accommodate changes in weight) throughout the study. Note: patients are allowed to take other medications (excluding other ribonucleic
acid [RNA] antisense or gene therapy agents) including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blocking agents (ARBs), * adrenergic blockers, potassium, and coenzyme Q,
provided they have been on a stable dose for 12 weeks prior to Week 1 and the dose is expected to remain constant throughout the study.
6. Achieved a mean 6MWT distance of *300 to *450 meters (without assistance) at both the Screening and Baseline visits (prior to Week 1). The mean 6MWT distance at the Screening and Baseline visits is the average of 2 separate assessments on 2 consecutive days at each visit. The Baseline mean (average of Baseline Days 1 and 2) must be within 15% of the Screening mean distance (average of Screening Days 1 and 2).
7. Sexually active subjects must agree to use contraceptives for the entire duration of the study and for 90 days following the last dose. Both a male condom and a medically acceptable form of female
contraceptive (e.g., oral contraceptives) must be used.
8. Has (a) parent(s) or legal guardian(s) who is (are) able to understand and comply with all the study requirements.
9. Is willing to provide informed assent (if applicable) and has (a) parent(s) or legal guardian(s) who is (are) willing to provide written informed consent for the patient to participate in the study.
1. Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks prior to Week 1 that may have an effect on muscle strength or function. Growth hormone for short stature and testosterone for delayed puberty are permitted if an endocrinologist has documented the diagnosis and medical necessity of treatment, and the patient has been on a stable dose for at least 24 weeks prior to Week 1.
2. Previous treatment with SMT C1100 (BMN-195) at any time.
3. Previous treatment with PRO045 or PRO053 within 24 weeks prior to Week 1.
4. Current or previous treatment with any other experimental treatment (other than deflazacort) within 12 weeks prior to Week 1.
5. Major surgery within 3 months prior to Week 1 or planned surgery for any time during this study, except for protocol-specified surgery, as applicable.
6. Presence of any other significant genetic disease other than DMD (e.g., dwarfism).
7. Presence of other clinically significant illness including significant cardiac, pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease, or malignancy.
8. Use of any aminoglycoside antibiotic or statin within 12 weeks prior to Week 1 or anticipated need for an aminoglycoside antibiotic or statin during the study.
9. LVEF <50% on the Screening echocardiogram (ECHO) or QTcF *450 msec based on the Screening and Baseline ECG.
10. Loss of *30 degrees of plantar flexion from the normal range of movement at the ankle joint due to contracture (i.e., fixed loss of more than 10 degrees of plantar flexion from plantigrade, assuming normal range of dorsiflexion of 20 degrees).
11. Prior or ongoing medical condition that could, in the Investigator*s opinion, adversely affect the safety of the patient, make it unlikely that the course of treatment would be completed, or impair the assessment of study results. Additionally, patients who seem unable / unwilling to comply with the study procedures, in the Investigator*s opinion, are to be excluded.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint:<br /><br>* Change from Baseline at Week 96 on the 6MWT for the combined-active group<br /><br>compared to placebo.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints:<br /><br>* Change from Baseline at Week 48 in the quantity of dystrophin protein<br /><br>expression as measured by Western blot of biopsied muscle tissue.<br /><br>* Change from Baseline at Week 48 in the intensity of dystrophin expression in<br /><br>biopsied muscle tissue, as measured by IHC.<br /><br>* Ability to rise independently from the floor (without external support) at<br /><br>Week 96, as indicated by an NSAA subscore of *2* (without modification) or<br /><br>*1* (Gower*s maneuver).<br /><br>* LOA status at Week 96, defined as an inability to perform the 6MWT, or a<br /><br>result of *0* meters on 6MWT.<br /><br>* Change from Baseline at Week 96 in:<br /><br>o NSAA total score<br /><br>o FVC% predicted<br /><br>o Frequency of falls<br /><br>o LVEF</p><br>