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

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

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.

Study Overview

• Status: Completed
• Conditions: Muscular Dystrophies
• Intervention / Treatment: Drug: GSK2402968; Drug: matched placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • WEstmead, New South Wales, Australia, 2145
      • GSK Investigational Site
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • GSK Investigational Site
• Belgium
  • Gent, Belgium, 9000
    • GSK Investigational Site
• France
  • Paris cedex 13, France, 75651
    • GSK Investigational Site
• Germany
  • Baden-Wuerttemberg
    • Freiburg, Baden-Wuerttemberg, Germany, 79106
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45122
      • GSK Investigational Site
• Israel
  • Jerusalem, Israel, 91240
    • GSK Investigational Site
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • GSK Investigational Site
• Spain
  • Esplugues (Barcelona), Spain, 08950
    • GSK Investigational Site
  • Valencia, Spain, 46009
    • GSK Investigational Site
• Turkey
  • Ankara, Turkey, 06100
    • GSK Investigational Site
• United Kingdom
  • London, United Kingdom, WC1N 1EH
    • GSK Investigational Site
  • Newcastle upon Tyne, United Kingdom, NE1 3BZ
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Continuous regimen; 6mg/kg once weekly; Once Weekly	Drug: GSK2402968; Subcutaneous injection; Other Names: 968; Drug: matched placebo; Subcutaneous injection; Other Names: Placebo
Experimental: 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	Drug: GSK2402968; Subcutaneous injection; Other Names: 968; Drug: matched placebo; Subcutaneous injection; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the efficacy of 2 different dosing regimens of subcutaneous GSK2402968 administered over 24 weeks in ambulant subjects with DMD	48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the safety and tolerability of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects	one year
To assess the PK of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects with DMD	48 weeks
To assess long term efficacy of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects with DMD	one year

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: June 29, 2010
• First Submitted That Met QC Criteria: June 29, 2010
• First Posted (Estimate): June 30, 2010

Study Record Updates

• Last Update Posted (Estimate): August 25, 2014
• Last Update Submitted That Met QC Criteria: August 21, 2014
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: DMD; muscular dystrophy; duchenne; 968
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: 114117