A research study of a new investigational medicinal product for the treatment of Duchenne Muscular Dystrophy patients
- Conditions
- Patients with Duchenne Muscular Dystrophy Amenable to Exon 45 or 53 SkippingMedDRA version: 20.0Level: PTClassification code 10013801Term: Duchenne muscular dystrophySystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2015-002069-52-GR
- Lead Sponsor
- Sarepta Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Male
- Target Recruitment
- 222
1. Is a male with an established clinical diagnosis of DMD and an out-offrame
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), ß 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.
Acceptable methods of contraception include combined (estrogen and
progesterone containing) hormonal contraception associated with
inhibition of ovulation (oral, intravaginal or transdermal); progesterone -
only hormonal contraception associated with inhibition of ovulation
(oral, injectable, or implantable); intrauterine device; intrauterine
hormone-releasing system; bilateral tubal occlusion, vasectomized
partner; sexual abstinence (True abstinence: when this is in line with the
preferred and usual lifestyle of the subject. Periodic abstinence: such as
calendar, ovulation, symptothermal, post-ovulation methods] and
withdrawal are not acceptable methods of contraception); or condom in
combination with either cap, diaphragm, or sponge with spermicide
(double-barrier contraception).
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
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)
- 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 -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 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 th
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method