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 Study to Assess the Safety, Tolerability and Preliminary Efficacy of ASP0367 (MA-0211) in Pediatric Male Participants With Duchenne Muscular Dystrophy (DMD)

Eligibility criteria:
Inclusion Criteria:

          -  Subject has a diagnosis of Duchenne muscular dystrophy (DMD) (confirmed by Central
             Genetic Counselor) defined as a clinical picture consistent with typical DMD and 1 of
             the following:

               -  Dystrophin immunofluorescence and/or Western blot showing severe dystrophin
                  deficiency consistent with the diagnosis of DMD.

               -  Identifiable mutation within the DMD gene (deletion/duplication of 1 or more
                  exons), where reading frame can be predicted as "out-of-frame"

               -  Complete dystrophin gene sequencing showing an alteration (point mutation,
                  duplication or other) that is expected to preclude production of the functional
                  dystrophin protein (i.e., nonsense mutation or deletion/duplication leading to a
                  downstream stop codon).

          -  A male subject of reproductive potential (Tanner Stage 2 and above) must agree to do
             either of the following from screening throughout the study until 30 days after the
             last dose of the investigational product (IP):

               -  Abstain from sexual intercourse, OR

               -  If having heterosexual intercourse, must use a condom and their female partners
                  who are of childbearing potential must use a highly effective contraception
                  method.

          -  Subject has been on a stable daily dose of corticosteroids for 6 months prior to the
             time of enrollment (at baseline).

          -  Subject has been on stable cardiac therapy for 3 months prior to the time of
             enrollment (at baseline), if used, which may include prophylactic
             angiotensin-converting enzyme inhibitors (ACE), angiotensin II receptor blocker (ARB),
             aldosterone receptor antagonists (e.g., spironolactone, eplerenone), and/or
             beta-blocker therapy or a combination therapy thereof.

          -  Subject is unable to complete the 10 meter run/walk in <10 seconds at screening.

          -  Subject has a PUL 2.0 entry item A score of 4, 5 or 6 at screening.

          -  Subject and subject's parent(s) or legal guardian agrees not to participate in another
             interventional study while participating in the present study.

          -  For those subjects receiving exon-skipping therapy, the subject has been on a stable
             dose regimen with a single commercially-available product for at least 6 months prior
             to randomization at baseline.

        Exclusion Criteria:

          -  Subject has had an acute illness (i.e., upper respiratory or viral infection) within 4
             weeks prior to study enrollment (at baseline), which precludes participation.

          -  Subject has a cardiac ejection fraction < 55% on echocardiogram at screening.

          -  Subject has a mean QT interval from triplicate electrocardiogram (ECG) using
             Fridericia's correction (QTcF) of > 450 msec at screening. If the mean QTcF exceeds
             the limits stated above, 1 additional triplicate ECG can be taken and utilized at
             screening.

          -  Subject has cardiac troponin I (cTnI) above the upper limit of normal (ULN) (or
             cardiac troponin T [cTnT] above the ULN if cTnI is not available immediately) at
             screening.

          -  Subject has used coenzyme Q10 (CoQ10), metformin, idebenone, carnitine, or other
             mitochondrial focused supplements or drugs within 4 weeks prior to randomization at
             baseline. In addition, subject has used any peroxisome proliferator-activated
             receptors (PPAR) ligands such as fibrates and thiazolidinediones 4 weeks prior to
             randomization at baseline.

          -  Subject has a known or suspected hypersensitivity to ASP0367, or any components of the
             formulation used.

          -  Subject has inadequate renal function, as defined by serum Cystatin C > 2 x ULN at
             screening.

          -  Subject who has any of the following liver function tests elevated: gamma-glutamyl
             transferase [GGT] and/or total bilirubin [TBL]) > 1.5 x ULN at screening.

          -  Subject who has a positive test result for hepatitis B surface (HBs) antigen,
             hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV)
             antigen/antibody at screening.

          -  Subject has mental conditions such as schizophrenia, bipolar disorder or major
             depressive disorder.

          -  Subject has a history of suicide attempt, suicidal behavior or has any suicidal
             ideation within 1 year prior to screening that meets criteria at a level of 4 or 5 by
             using the Columbia Suicide Severity Rating Scale (C-SSRS) or who is at significant
             risk to commit suicide, as assessed at screening or at baseline.

          -  Subject has severe behavioral or cognitive problems that preclude participation in the
             study.

          -  Subject has any condition, which makes the subject unsuitable for study participation.

          -  Subject is taking any other investigational therapy currently or has taken any other
             investigational therapy within 3 months prior to the time of enrollment (at baseline).

          -  Subject and parent/guardian are unwilling and unable to comply with scheduled visits,
             IP administration plan and study procedures.

          -  Subject has had clinical signs and symptoms consistent with coronavirus (SARSCoV-2)
             infection or who has tested positive within 2 months prior to randomization at
             baseline.

          -  Subject whose parent(s) and/or caregiver(s) have increased risk of coronavirus
             (SARS-CoV-2) exposure from work history (e.g., nursing home, meat processing facility
             and correctional facility) or recent travel history unless the subject's parent(s)
             and/or caregiver(s) have been appropriately vaccinated with one of the COVID-19
             vaccines.
Male
No healthy subjects accepted to join the trial.
Subject must be at least 8 Years old.
Subject must be at most 16 Years

Eligibility (NLI label): Entailment