Study of DS-5141b in Patients With Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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This is a phase I/II study to evaluate the safety, tolerability, efficacy, and pharmacokinetic (PK) profile of DS-5141b in patients with Duchenne muscular dystrophy (DMD) amenable to exon 45 skipping and to determine the dosage for subsequent studies.

Official Title
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Phase I/II Study of DS-5141b: Open-label Study of DS-5141b in Patients With Duchenne Muscular Dystrophy

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: DS-5141b


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmation of out-of-frame deletion(s) that could be corrected by dystrophin gene exon 45 skipping. Intact muscles of adequate quality for biopsy to allow evaluation of the efficacy of the study drug. Boys aged from 5 years to <11 years. Patients able to walk at least 325 meters in the 6-minutes walk test. Glucocorticoid-naive patients, or patients who have used glucocorticoids for at least 6 months prior to enrollment in this study with no dose changes for at least 3 months prior to enrollment. Exclusion Criteria: A genetic mutation that can not be expected the expression of dystrophin protein by dystrophin gene exon 45 skipping. A concurrent illness other than DMD that can cause muscle weakness and/or impairment of motor function. Current or history of severe disorder. Left ventricular ejection fraction (LEVF) <55%. Corrected QT interval (QTc) >0.45 sec.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 10 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DS-5141b<br>DS-5141b, Subcutaneous injection Part 1: DS-5141b will be injected subcutaneously once a week for 2 weeks at the following dose levels. Dose escalation will be performed. DS-5141b will be administered at dose levels 1 and 3 in Cohort 1 and at dose levels 2 and 4 in Cohort 2. Level 1: 0.1 mg/kg Level 2: 0.5 mg/kg Level 3: 2.0 mg/kg Level 4: 6.0 mg/kg Part 2: Two doses of DS-5141b will be selected based on the results obtained in Part 1. Each selected dose will be administered subcutaneously once a week for 12 weeks. Part 2-Extension: Two doses, 2.0 mg/kg or 6.0 mg/kg, of DS-5141b will be administered subcutaneously once a week for 48 weeks. | Drug: DS-5141b<br>* DS-5141b, Subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent adverse events (TEAEs) by the end of the trial | TEAEs are adverse events (including clinically significant laboratory values) temporally associated with use of DS-5141b, whether or not attributable to the product. | 48 Weeks of Part 2-Extension | 
| Maximum concentration (Cmax) of DS-5141b |  | Week 48 of Part 2-Extension | 
| Area under the curve (AUC) for DS-5141b |  | Week 48 of Part 2-Extension | 
| Time to maximum concentration (Tmax) of DS-5141b |  | Week 48 of Part 2-Extension | 
| Half-life (T1/2) of DS-5141b |  | Week 48 of Part 2-Extension | 
| Dystrophin protein expression in muscle tissue |  | Week 48 of Part 2-Extension | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Production of exon 45-skipped dystrophin mRNA in muscle tissue |  | Week 48 of Part 2-Extension | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Duchenne muscular dystrophy, DMD, Oligonucleotides, Antisense, Exon skipping