Patient case (clinical description): An 8-year-old boy is brought to the clinic by his parents because of weakness and difficulty of standing up from a sitting position. The mother is healthy but had a brother who died in his 20th after being disabled and using wheelchairs in the last few years of his life. Physical examination shows 3/5 lower extremity muscle strength and enlarged calf muscles. The other physical examination and vital signs are unremarkable. Muscle biopsy showed absence of dystrophin protein. The patient is diagnosed with DMD.

Patient's own account: I brought my  8-year-old son to the doctor's clinic. He was struggling to stand up from a chair for the past few days. My wife is healthy but she was pretty worried since his brother died in his 20s after being disabled and using a wheelchair for the last years of his life. The doctor did an exam which highlighted weakness in the leg muscles and unusually large calf muscles. The rest of the exam was fine, and his vitals were normal. My son did a muscle biopsy, and it showed that the protein important for muscle strength and function is missing. The doctor diagnosed him with Duchenne muscular dystrophy.

Clinical trial: A Clinical Study to Assess Two Doses of GSK2402968 in Subjects With Duchenne Muscular Dystrophy (DMD)

Eligibility criteria:
Inclusion Criteria:

          -  Ambulant subjects with Duchenne muscular dystrophy (DMD) 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,

          -  Life expectancy of at least 1 year,

          -  Able to rise from floor in < or =15 seconds (without aids/orthoses) at Screening Visit
             1 and Screening Visit 2,

          -  Able to complete 6 Minute Walk Distance (6MWD) test with minimal distance of at least
             75 meters, with reproducible results (within 20% of each other) at Screening Visit 1,
             Screening Visit 2 and at the baseline visit prior to randomization,

          -  Receiving oral 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 48 week
             duration of the study (Dose adjustments that are based on weight changes are
             permitted),

          -  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

          -  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).

        Exclusion Criteria:

          -  Any additional missing exon for DMD that cannot be treated with GSK2402968,

          -  Current or history of liver disease or impairment including :

               1. an INR vaue above 1.5 is in and of itself exclusionary

               2. a total bilirubin greater than 2 times the Upper Limit of Normal is in and of
                  itself exclusionary

               3. a GGT greater than 2 times the Upper Limit of Normal is in and of itself
                  exclusionary

          -  Current or history of renal disease or impairment,

          -  Baseline platelet count below the Lower Limit of Normal,

          -  aPPT above the Upper Limit of Normal,

          -  History of significant medical disorder which may confound the interpretation of
             either efficacy or safety data e.g. inflammatory disease

          -  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, 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
Male
No healthy subjects accepted to join the trial.
Subject must be at least 5 Years old.


Eligibility (NLI label): Entailment