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
- Duchenne muscular dystrophymuscle disorder1002839610028377
- Registration Number
- NL-OMON51496
- Lead Sponsor
- Sarepta Therapeutics, Inc.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 2
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 prior to screening by a genetic report from an accredited
laboratory defining deletion endpoints by multiplex ligation-dependent probe
amplification or sequencing. The patient*s amenability to exon 45 or exon 53
skipping must be confirmed prior to first dose using the genotyping results
obtained during Screening.
2. Is between 6 and 13 years of age, inclusive, at randomization for patients
amenable to exon 53 skipping; or is between 7 and 13 years of age, inclusive,
at randomization for patients amenable to exon 45 skipping.
3. Has stable pulmonary function (FVC % of predicted *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 brachii 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
throughout the study (except for modifications to accommodate changes in
weight).
6. If taking angiotensin-converting enzyme (ACE) inhibitors, angiotensin
receptor blocking agents (ARBs), * adrenergic blockers, aldosterone receptor
antagonists, potassium, or coenzyme Q, has been on a stable dose for at least
12 weeks prior to Week 1 and the dose is expected to remain constant throughout
the study (except for modifications to accommodate changes in weight).
7. 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).
8. If sexually active, agrees to use a male condom during such activity for the
entire duration of the study and for 90 days after the last dose. The sexual
partner must also use a medically acceptable form of contraceptive (eg, female
oral contraceptives) during this time frame.
9. Has (a) parent(s) or legal guardian(s) who is (are) able to understand and
comply with all the study requirements.
10. 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. Treatment with any of the following investigational therapies according to
the time frames specified:
* At any time:
o Utrophin upregulating agents (except for Ezutromid)
o CRISPR/Cas9, or any other form of gene editing
o Gene therapy
o Cell-based therapy (eg, stem cell transplantation)
o Any form of nucleic acid antisense therapy, except PRO045 (BMN 045) or PRO053
(BMN 053) (see below)
o Exon Skipping Therapies
- Drisapersen within 36 weeks prior to Week 1
- PRO045 (BMN 045) Within 24 weeks prior to Week 1
- PRO053 (BMN 053)Within 24 weeks prior to Week 1
- PRO051 (BMN 051) Within 24 weeks prior to Week 1
* All Anti-Myostatin Therapies within 24 Weeks prior to Week 1 including
but not limited to:
o Domagrozumab (PF-06252616)
o RG-6206 (formally RO-7239361 and BMS-986089)
* Small Molecule Therapies:
o Ezutromid (SMT C1100) within 1 week prior to Week 1
* Within 24 weeks prior to Week 1:
o Anti-fibrotic or anti-inflammatory agents including but not limited to:
rimeporide, epigallocatechin-gallate, TAS-205, edasalonexent (CAT-1004),
FG-3019, and halofuginone (HT-100)
o Mast cell activation inhibitor (eg, CRD007 [pemirolast sodium])
o Idebenone (Raxone®)
* Within 12 weeks prior to Week 1:
o Nitric oxide (NO)-active agents including, but not limited to, metformin and
citrulline, isosorbide dinitrate, tadalafil, sildenafil, pentoxifylline if
taken as part of a DMD clinical trial and not for a medical indication. If
taken for a medical indication, must be on a stable dose for at least 12 weeks
prior to Week 1.
o Vamorolone (VBP-15)
* For any experimental treatment not otherwise specified in Exclusion Criterion
1, consult the medical monitor.
2. Treatment with any of the following non-investigational therapies according
to the time frames specified:
* Within 12 weeks prior to Week 1:
o Any pharmacologic treatment (other than corticosteroids) that may have an
effect on muscle strength or function. Growth hormone for short stature and
testosterone for delayed puberty are permitted if a physician has documented
the diagnosis and medical necessity of treatment, and the patient started
dosing at least 24 weeks prior to Week 1.
* Within 12 weeks prior to Week 1 or anticipated need during the study:
o Statins
o Aminoglycoside antibiotics
3. 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.
4. Presence of any other significant genetic disease other than DMD (eg,
dwarfism).
5. Presence of other clinically significant illness including significant
cardiac, pulmonary, hepatic, renal, hematologic, immunologic, or behavioral
disease, or malignancy.
6. LVEF <50% on the Screening echocardiogram (ECHO) or QTcF *450 msec on the
Screening and Baseline electrocardiogram (ECG).
7. Dorsiflexion range of motion will be measured bilaterally and recorded as
degrees from neutral (see figure). The subject will be excluded if the average
loss of dorsiflexion of both extremities is > -10 degrees. For example, if
the subject has -8 degrees on one side and -12 degrees on the other side, then
he would still qualify because the average of the 2 sides is -10 degrees.
8. Prior or ongoing medical condition that could, in the Investigator*s
opinion, adversely affec
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Double-blind period: Change from Baseline at Week 96 on the 6MWT for the<br /><br>combined-active group compared to placebo. </p><br>
- Secondary Outcome Measures
Name Time Method