Clinical trial NCT02667483: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Duchenne Muscular Dystrophy
Keywords: Duchenne muscular dystrophy
DMD
Oligonucleotides, Antisense
Exon skipping
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2016-01-29
Enrollment: 8
Sex: MALE
Minimum age (years): 5
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) In Participants With Duchenne Muscular Dystrophy
timeFrame: 48 Weeks of Part 2-Extension-2
measure: Pharmacokinetic Parameter Maximum Concentration (Cmax) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy
timeFrame: Week 48 of Part 2-Extension-2
measure: Pharmacokinetic Parameter Area Under the Curve (AUC) Tau of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy
timeFrame: Week 48 of Part 2-Extension-2
measure: Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy
timeFrame: Week 48 of Part 2-Extension-2
measure: Pharmacokinetic Parameter Half-life (T1/2) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Dystrophy
timeFrame: Week 48 of Part 2-Extension-2
measure: Mean Dystrophin Protein Expression in Muscle Tissue
timeFrame: Week 48 of Part 2-Extension-2
Secondary outcomes:
measure: Number of Participants With Exon 45-skipped Dystrophin mRNA Expression in Muscle Tissue Posttreatment
timeFrame: Week 48 of Part 2-Extension-2
Other outcomes:
Locations:
city: Hyogo
country: Japan
facility: Kobe University Hospital
state: Kobe-shi
city: Tokyo
country: Japan
facility: National Center of Neurology and Psychiatry
state: Kodaira-shi
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: