Phase II Doubleblind Exploratory Study of GSK2402968 in Ambulant Subjects With Duchenne Muscular Dystrophy

NCT ID: NCT01153932

Last Updated: 2014-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2012-09-30

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.

Conditions

Muscular Dystrophies

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Continuous regimen; 6mg/kg once weekly

Once Weekly

Group Type: EXPERIMENTAL

GSK2402968

Intervention Type: DRUG

Subcutaneous injection

matched placebo

Intervention Type: DRUG

Subcutaneous injection

Intermittent regimen; 6mg/kg twice weekly

Twice weekly on 1st, 3rd and 5th weeks, once weekly on 2nd, 4th and 6th weeks, and no active drug on 7th to 10th week of each 10 week cycle

Group Type: EXPERIMENTAL

GSK2402968

Intervention Type: DRUG

Subcutaneous injection

matched placebo

Intervention Type: DRUG

Subcutaneous injection

Interventions

GSK2402968

Subcutaneous injection

Intervention Type: DRUG

matched placebo

Subcutaneous injection

Intervention Type: DRUG

Other Intervention Names

968; Placebo

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

• Minimum Eligible Age: 5 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Westmead, New South Wales, Australia

GSK Investigational Site

Parkville, Victoria, Australia

GSK Investigational Site

Ghent, , Belgium

GSK Investigational Site

Paris, , France

GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Jerusalem, , Israel

GSK Investigational Site

Nijmegen, , Netherlands

GSK Investigational Site

Esplugues (Barcelona), , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Ankara, , Turkey (Türkiye)

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Newcastle upon Tyne, , United Kingdom

Countries

Australia; Belgium; France; Germany; Israel; Netherlands; Spain; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 25209738 (View on PubMed)

Other Identifiers

114117

Identifier Type: -

Identifier Source: org_study_id