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

Phase 1

Completed

• Conditions: Duchenne Muscular Dystrophy
• Interventions: Drug: DS-5141b

• Registration Number: NCT02667483
• Lead Sponsor: Daiichi Sankyo Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-10
• Study First Submitted: 2016-01-26
• Study First Submitted QC: 2016-01-28
• Study First Posted: 2016-01-29
• Primary Completion: 2020-10-20
• Study Completion: 2020-10-20
• Status Verified: 2023-07
• Results First Submitted: 2023-07-28
• Results First Submitted QC: 2023-07-28
• Last Update Submitted: 2023-07-28
• Results First Posted: 2024-03-07
• Last Update Posted: 2024-03-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 8

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DS-5141b	DS-5141b	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-2: Two doses, 2.0 mg/kg or 6.0 mg/kg, of DS-5141b will be administered subcutaneously once a week for 48 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) In Participants With Duchenne Muscular Dystrophy	48 Weeks of Part 2-Extension-2	A treatment-emergent adverse event (TEAE) is defined as an adverse event that emerges during treatment having been absent prior to treatment or reemerges during treatment or worsens in severity during treatment.
Pharmacokinetic Parameter Maximum Concentration (Cmax) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy	Week 48 of Part 2-Extension-2	Pharmacokinetic parameters were assessed using non-compartmental methods.
Pharmacokinetic Parameter Half-life (T1/2) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Dystrophy	Week 48 of Part 2-Extension-2	Pharmacokinetic parameters were assessed using non-compartmental methods.
Mean Dystrophin Protein Expression in Muscle Tissue	Week 48 of Part 2-Extension-2
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy	Week 48 of Part 2-Extension-2	Pharmacokinetic parameters were assessed using non-compartmental methods.
Pharmacokinetic Parameter Area Under the Curve (AUC) Tau of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy	Week 48 of Part 2-Extension-2	Pharmacokinetic parameters were assessed using non-compartmental methods.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Exon 45-skipped Dystrophin mRNA Expression in Muscle Tissue Posttreatment	Week 48 of Part 2-Extension-2

Trial Locations

Locations (2)

Kobe University Hospital; 🇯🇵 Hyogo, Kobe-shi, Japan

National Center of Neurology and Psychiatry; 🇯🇵 Tokyo, Kodaira-shi, Japan