Clinical trial: Exploratory Study of NS-089/NCNP-02 in DMD (NCT04129294)

Eligibility criteria:
Inclusion Criteria:

          -  Has an out of frame deletion(s) that could be corrected by skipping exon 44 as
             confirmed by any of methodology at the time of visit 1. If not confirmed by any of
             methodology that evaluates the relative copy number of all exons (i.e. MLPA etc), must
             be confirmed through these techniques by the time of visit 3.

          -  DNA sequencing of exon 44 confirms that no DNA polymorphisms occur that could
             compromise duplex formation between NS-089/NCNP-02 and pre-mRNA.

          -  Male and >= 8 years and < 17 years of age at the time of obtaining informed consent
             and/or assent. Subjects aged >= 4 years and < 8 years can be enrolled according to the
             circumstances.

          -  Able to give informed consent in writing signed by parent(s) or legal guardian who is
             able to understand all of the study procedure requirements. If applicable, able to
             give informed assent in writing signed by the subject.

          -  Life expectancy of at least 1 year

          -  Able to ambulate. Non-ambulant subject can be enrolled according to the circumstances.

          -  Have intact muscles, which have adequate quality for biopsy. (No lacks or severe
             atrophy of biceps brachii or tibialis anterior muscle)

          -  QTc <450 msec (based on 12-lead ECGs), or <480 msec for subject with Bundle Branch
             Block.

          -  Glucocorticoid-naive patients, or patients who have used systemic glucocorticoids for
             at least 6 months prior to enrollment in this study with no dose changes for at least
             3 months prior to enrollment.

        Exclusion Criteria:

          -  Has participated in other pharmacological clinical trial that might recover dystrophin
             protein by the readthrough or the exon-skipping therapy, and/or upregulate the
             dystrophin-associated proteins such as utrophin.

          -  A forced vital capacity (FVC) < 50% of predicted.

          -  Continuous use of artificial respirator (except for use of NPPV while sleeping)

          -  A left ventricular ejection fraction (EF) < 40% or fractional shortening (FS) < 25%
             based on echocardiogram (ECHO).

          -  Surgery within the last 3 months prior to the first anticipated administration of
             study medication or planned for anytime between visit 1 of Part 1 and the last visit
             of Part 2.

          -  Positive hepatitis B surface antigen (HbsAg), hepatitis C antibody test (HCV), or
             human immunodeficiency virus (HIV) test at screening.

          -  Current diagnosis of any immune deficiency or autoimmune disease.

          -  Current diagnosis of any active or uncontrolled infection, cardiomyopathy, or liver or
             renal disease.

          -  Use of any other investigational agents and/or experimental agents within 3 months
             prior to the first anticipated administration of study medication.

          -  History of any severe drug allergy.
Male
No healthy subjects accepted to join the trial.
Subject must be at least 4 Years old.
Subject must be at most 17 Years

Patient description (medical language): 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 description (patient's own words): 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.

Does the patient match the trial criteria? 1