Study of DS-5141b in Patients With Duchenne Muscular Dystrophy
Phase I/II Study of DS-5141b: Open-label Study of DS-5141b in Patients With Duchenne Muscular Dystrophy
PhasePhase 1/Phase 2
Lead SponsorDaiichi Sankyo
StatusCompleted No Results Posted
Indication/ConditionDuchenne Muscular Dystrophy
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.
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.
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.