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 Skipping.MedDRA version: 20.0Level: PTClassification code: 10013801Term: Duchenne muscular dystrophy Class: 100000004850Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- CTIS2024-514698-23-00
- Lead Sponsor
- Sarepta Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 328
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., 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., 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., 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., Has intact right and left biceps brachii muscles (the preferred biopsy site) or 2 alternative upper arm muscle groups., 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), 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)., 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 business 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)., 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 spe
Treatment with any of the following investigational therapies according to the time frames specified: ? At any time: - Utrophin upregulating agents (except for Ezutromid) - CRISPR/Cas9, or any other form of gene editing - Gene therapy - Cell-based therapy (e.g., stem cell transplantation) - 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: - Domagrozumab (PF-06252616) - RG-6206 (formally RO-7239361 and BMS-986089) ? Small Molecule Therapies: - Ezutromid (SMT C1100) within 1 week prior to Week 1 ? Within 24 weeks prior to Week 1: - Anti-fibrotic or anti-inflammatory agents including but not limited to: rimeporide, epigallocatechin-gallate, TAS-205, edasalonexent (CAT1004), FG-3019, and halofuginone (HT-100) - Mast cell activation inhibitor (e.g., CRD007 [pemirolast sodium]) - Idebenone (Raxone®) ? Within 12 weeks prior to Week 1: - 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. - Vamorolone (VBP-15) ? For any experimental treatment not otherwise specified in Exclusion Criterion 1, consult the medical monitor., Treatment with any of the following non-investigational therapies according to the time frames specified: ? Within 12 weeks prior to Week 1: - 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: - Statins - Aminoglycoside antibiotics, 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., Presence of any other significant genetic disease other than DMD (e.g., dwarfism)., Presence of other clinically significant illness including significant cardiac, pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease, or malignancy., LVEF <50% on the Screening echocardiogram (ECHO) or QTcF =450 msec based on the Screening and Baseline electrocardiogram (ECG)., 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., 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 procedure
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