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

NCT02667483 | Completed Phase 1 Results

• 2 other identifiers: DS5141-A-J101153072
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

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.

Conditions

Duchenne Muscular Dystrophy

Keywords

Duchenne muscular dystrophy; DMD; Oligonucleotides, Antisense; Exon skipping

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (1)

• Number of Participants With Exon 45-skipped Dystrophin mRNA Expression in Muscle Tissue Posttreatment

  Week 48 of Part 2-Extension-2

Study Arms (1)

DS-5141b

EXPERIMENTAL

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

Interventions

DS-5141b DRUG

DS-5141b, Subcutaneous injection

DS-5141b

Eligibility Criteria

• Age: 5 Years - 10 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Daiichi Sankyo Co., Ltd.: lead
• Daiichi Sankyo: collaborator

Study Sites (2)

Kobe University Hospital

Hyōgo, Kobe-shi, 650-0017, Japan

Location

National Center of Neurology and Psychiatry

Tokyo, Kodaira-shi, 187-8551, Japan

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2016
• First Posted: January 29, 2016
• Study Start: October 1, 2015
• Primary Completion: October 20, 2020
• Study Completion: October 20, 2020
• Last Updated: March 7, 2024
• Results First Posted: March 7, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

JP (2)