A Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
Condition: Muscular Dystrophies
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne
Intervention: GSK2402968 6mg/kg/week
Intervention description: subcutaneous
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 186.0
Sex: Male
Minimum age: 5 Years
Healthy volunteers: No
Keywords: Duchenne Muscular Dystrophy; DMD; 968; GSK; Duchenne

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.