a clinical study to assess the efficacy and safety of gsk2402968 in subjects with duchenne muscular dystrophy

Conditions: Muscular Dystrophies

Summary: 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.


Eligibility 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.

Keywords: duchenne muscular dystrophy dmd 968 gsk duchenne