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A Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy (DMD114044)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01254019
First received: October 21, 2010
Last updated: October 23, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to determine whether GSK2402968 is effective in the treatment of ambulant boys with Duchenne muscular dystrophy resulting from a mutation thought to be corrected by exon 51 skipping.


Condition Intervention Phase
Muscular Dystrophies
Drug: GSK2402968 6mg/kg/week
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Double Blind, Placebo-controlled Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • To assess the efficacy of subcutaneous 6 mg/kg GSK2402968 versus placebo; specifically to have 90% power to detect a difference in 6MWD between GSK2402968 and placebo of 30 meters, assuming a common standard deviation of 55meters [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the safety and tolerability of subcutaneous 6 mg/kg GSK2402968 with respect to AEs, ECG results, vital signs and laboratory tests [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Plasma concentration of subcutaneous 6 mg/kg GSK2402968 calculated at each time point for each subject (sample size (n), mean, standard deviation (SD), percentage of coefficient of variation (%CV), geometric mean, median, minimum, and maximum [ Time Frame: one year ] [ Designated as safety issue: No ]
  • To evaluate the difference on quality of life of between GSK2402968 and placebo using PedsQOL, CGI-I and HUI [ Time Frame: one year ] [ Designated as safety issue: No ]

Enrollment: 186
Study Start Date: December 2010
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK2402968
6mg/kg
Drug: GSK2402968 6mg/kg/week
subcutaneous
Experimental: Placebo
dose-matched
Drug: GSK2402968 6mg/kg/week
subcutaneous

  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ambulant subjects with Duchenne muscular dystrophy resulting from a mutation/deletion within 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), SCAIP (Single Condition Amplification/Internal Primer) or H-RMCA (High-Resolution Melting Curve Analysis), and correctable by GSK2402968-induced DMD exon 51 skipping.
  • Males, aged at least 5 years, and with life expectancy of at least 1 year
  • Able to complete 6MWD test with minimal distance of at least 75m at each predrug visit. In addition, results of 6MWD must be within 20% of each other at each pre-drug visit
  • 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 (based on single or average QTc value of triplicate ECGs obtained over a brief recording period), or <480 msec for subjects with Bundle Branch Block. Note: QTc may be either QTcB or QTcF, and machine read or manual overread.
  • Subjects, where appropriate, must be willing to use adequate contraception (condoms or abstinence) for the duration of the study and for at least 5 months after the last dose of study drug.
  • Willing and able to comply with all protocol requirements and procedures,
  • Able to give informed assent and/or consent in writing signed by the subject and/or parent(s)/legal guardian (according to local regulations).
  • French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

  • Any additional missing exon for DMD that cannot be treated with GSK2402968
  • Current or history of liver or renal disease or impairment
  • Acute illness within 4 weeks of the first anticipated administration of study medication which may interfere with study assessments
  • Use of anticoagulants, antithrombotics or antiplatelet agents, previous treatment with investigational drugs, within 6 months of the first administration of study medication; and idebenone or other forms of Coenzyme Q10 within 1 month of the first administration of study medication.
  • Current or anticipated participation in any investigational clinical studies
  • Positive hepatitis B surface antigen, hepatitis C antibody test (if verified via RIBA or PCA testing), or human immunodeficiency virus (HIV) test at screening,
  • Symptomatic cardiomyopathy. If subject has a left ventricular ejection fraction <45% at Screening, the investigator should discuss inclusion of subject in the study with the medical monitor,
  • Children in Care. The definition of a Child in Care is a child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. The definition of a child in care can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The definition of a child in care does not include a child who is adopted or has an appointed legal guardian.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01254019

  Show 47 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01254019     History of Changes
Other Study ID Numbers: 114044
Study First Received: October 21, 2010
Last Updated: October 23, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Canada: Health Canada
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
Europe: European Medicines Agency

Keywords provided by GlaxoSmithKline:
Duchenne Muscular Dystrophy
DMD
968
GSK
Duchenne

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Muscular Diseases
Muscular Disorders, Atrophic
Musculoskeletal Diseases
Nervous System Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on November 27, 2014