Clinical trial NCT01153932: Phase II Doubleblind Exploratory Study of GSK2402968 in Ambulant Subjects With Duchenne Muscular Dystrophy
Official title: A Phase II, Double Blind, Exploratory, Parallel-group, Placebocontrolled Clinical Study to Assess Two Dosing Regimens of GSK2402968 for Efficacy, Safety, Tolerability and Pharmacokinetics in Ambulant Subjects With Duchenne Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Muscular Dystrophies
Keywords: 968
muscular dystrophy
duchenne
DMD
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-06-30
Enrollment: 53
Sex: MALE
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether GSK2402968 given as a continuous dose and as an intermittent dose is effective and safe in the treatment of Duchenne muscular dystrophy.

Detailed description: This is a phase II, double-blind, exploratory, parallel-group, placebo-controlled clinical study in ambulant subjects with DMD resulting from a mutation that can be corrected by exon skipping induced by GSK2402968. The study aims to randomise 54 subjects. There will be 2 parallel cohorts. Each cohort will include subjects on GSK2402968 and matched placebo in a 2:1 ratio.

Eligibility criteria: Inclusion Criteria:

* Ambulant subjects with Duchenne muscular dystrophy resulting from a mutation in the DMD gene, confirmed by a state-of-the-art DNA diagnostic technique covering all DMD gene exons, including but not limited to MLPA (Multiplex Ligation-dependent Probe Amplification), CGH (Comparative Genomic Hybridisation) or H-RMCA (High-Resolution Melting Curve Analysis), and correctable by GSK2402968-induced DMD exon 51 skipping,
* Males, at least 5 years of age and with a life expectancy of at least 1 year
* Able to rise from floor in ≤7 seconds (without aids/orthoses),
* Able to complete the 6MWD test with a distance of at least 75m
* Receiving glucocorticoids for a minimum of 6 months immediately prior to screening, with no significant change in total daily dosage or dosing regimen for a minimum of 3 months immediately prior to screening and a reasonable expectation that total daily dosage and dosing regimen will not change significantly for the duration of the study
* QTc \<450msec
* On adequate contraception
* Able to comply with and complete all protocol requirements

Exclusion Criteria:

* any additional missing exon for DMD
* Current of history of liver or renal disease or impairment
* Acute illness within 4 weeks of the first dose
* Use of prohibited meds within 6 months of fist dose
* Current participation in any other investigational clinical trial
* Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test at screening
* Symptomatic cardiomyopathy
* Children in Care

Primary outcomes:
measure: To assess the efficacy of 2 different dosing regimens of subcutaneous GSK2402968 administered over 24 weeks in ambulant subjects with DMD
timeFrame: 48 weeks
Secondary outcomes:
measure: To assess the safety and tolerability of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects
timeFrame: one year
measure: To assess the PK of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects with DMD
timeFrame: 48 weeks
measure: To assess long term efficacy of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects with DMD
timeFrame: one year
Other outcomes:
Locations:
city: WEstmead
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Parkville
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Paris cedex 13
country: France
facility: GSK Investigational Site
city: Freiburg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Jerusalem
country: Israel
facility: GSK Investigational Site
city: Nijmegen
country: Netherlands
facility: GSK Investigational Site
city: Esplugues (Barcelona)
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Ankara
country: Turkey
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Newcastle upon Tyne
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Voit T, Topaloglu H, Straub V, Muntoni F, Deconinck N, Campion G, De Kimpe SJ, Eagle M, Guglieri M, Hood S, Liefaard L, Lourbakos A, Morgan A, Nakielny J, Quarcoo N, Ricotti V, Rolfe K, Servais L, Wardell C, Wilson R, Wright P, Kraus JE. Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study. Lancet Neurol. 2014 Oct;13(10):987-96. doi: 10.1016/S1474-4422(14)70195-4. Epub 2014 Sep 7.