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

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.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: DS-5141b

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kobe-shi
    • Hyogo, Kobe-shi, Japan, 650-0017
      • Kobe University Hospital
  • Kodaira-shi
    • Tokyo, Kodaira-shi, Japan, 187-8551
      • National Center of Neurology and Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 10 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: DS-5141b; DS-5141b, Subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) In Participants With Duchenne Muscular Dystrophy	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.	48 Weeks of Part 2-Extension-2
Pharmacokinetic Parameter Maximum Concentration (Cmax) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy	Pharmacokinetic parameters were assessed using non-compartmental methods.	Week 48 of Part 2-Extension-2
Pharmacokinetic Parameter Area Under the Curve (AUC) Tau of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy	Pharmacokinetic parameters were assessed using non-compartmental methods.	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	Pharmacokinetic parameters were assessed using non-compartmental methods.	Week 48 of Part 2-Extension-2
Pharmacokinetic Parameter Half-life (T1/2) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Dystrophy	Pharmacokinetic parameters were assessed using non-compartmental methods.	Week 48 of Part 2-Extension-2
Mean Dystrophin Protein Expression in Muscle Tissue		Week 48 of Part 2-Extension-2

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.
• Collaborators: Orphan Disease Treatment Institute Co., Ltd.
• Investigators: Study Director: Global Clinical Leader, Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): October 20, 2020
• Study Completion (Actual): October 20, 2020

Study Registration Dates

• First Submitted: January 26, 2016
• First Submitted That Met QC Criteria: January 28, 2016
• First Posted (Estimated): January 29, 2016

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: DMD; Duchenne muscular dystrophy; Exon skipping; Oligonucleotides, Antisense
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: DS5141-A-J101; 153072 (Registry Identifier: JAPIC CTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No