Back to resultsStudy of DS-5141b in Patients With Duchenne Muscular Dystrophy
Primary Purpose
Duchenne Muscular Dystrophy
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
DS-5141b
Sponsored by
About this trial
This is an interventional treatment trial for Duchenne Muscular Dystrophy focused on measuring Duchenne muscular dystrophy, DMD, Oligonucleotides, Antisense, Exon skipping
Eligibility Criteria
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.
Sites / Locations
- Kobe University Hospital
- National Center of Neurology and Psychiatry
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
DS-5141b
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Maximum concentration (Cmax) of DS-5141b
Area under the curve (AUC) for DS-5141b
Time to maximum concentration (Tmax) of DS-5141b
Half-life (T1/2) of DS-5141b
Dystrophin protein expression in muscle tissue
Secondary Outcome Measures
Production of exon 45-skipped dystrophin mRNA in muscle tissue
Full Information
NCT ID
NCT02667483
First Posted
January 26, 2016
Last Updated
December 14, 2020
Sponsor
Daiichi Sankyo Co., Ltd.
Collaborators
Orphan Disease Treatment Institute Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT02667483
Brief Title
Study of DS-5141b in Patients With Duchenne Muscular Dystrophy
Official Title
Phase I/II Study of DS-5141b: Open-label Study of DS-5141b in Patients With Duchenne Muscular Dystrophy
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
October 2015 (Actual)
Primary Completion Date
October 20, 2020 (Actual)
Study Completion Date
October 20, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo Co., Ltd.
Collaborators
Orphan Disease Treatment Institute Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne Muscular Dystrophy
Keywords
Duchenne muscular dystrophy, DMD, Oligonucleotides, Antisense, Exon skipping
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DS-5141b
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
DS-5141b
Intervention Description
DS-5141b, Subcutaneous injection
Primary Outcome Measure Information:
Title
Number of participants with treatment-emergent adverse events (TEAEs) by the end of the trial
Description
TEAEs are adverse events (including clinically significant laboratory values) temporally associated with use of DS-5141b, whether or not attributable to the product.
Time Frame
48 Weeks of Part 2-Extension
Title
Maximum concentration (Cmax) of DS-5141b
Time Frame
Week 48 of Part 2-Extension
Title
Area under the curve (AUC) for DS-5141b
Time Frame
Week 48 of Part 2-Extension
Title
Time to maximum concentration (Tmax) of DS-5141b
Time Frame
Week 48 of Part 2-Extension
Title
Half-life (T1/2) of DS-5141b
Time Frame
Week 48 of Part 2-Extension
Title
Dystrophin protein expression in muscle tissue
Time Frame
Week 48 of Part 2-Extension
Secondary Outcome Measure Information:
Title
Production of exon 45-skipped dystrophin mRNA in muscle tissue
Time Frame
Week 48 of Part 2-Extension
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Leader
Organizational Affiliation
Daiichi Sankyo, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Kobe University Hospital
City
Hyogo
State/Province
Kobe-shi
ZIP/Postal Code
650-0017
Country
Japan
Facility Name
National Center of Neurology and Psychiatry
City
Tokyo
State/Province
Kodaira-shi
ZIP/Postal Code
187-8551
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of DS-5141b in Patients With Duchenne Muscular Dystrophy
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