A Randomized, Double Blind, Placebo-Controlled Phase 1b Study With Open-Label Extension to Assess the Safety, Tolerability and Preliminary Efficacy of ASP0367 (MA-0211) in Pediatric Male Patients With Duchenne Muscular Dystrophy (DMD)

Fecha de inicio: 24 de febrero de 2021

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 regimen 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 \<6 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. * For those subjects using metformin, the subject has been on a stable dose of metformin for 3 months prior to the time of enrollment (at baseline) and the investigator expects the subject to maintain the current metformin dose. 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 \< 53% 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) at screening and is assessed clinically significant. * Subject has used coenzyme Q10 (CoQ10), 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 A virus (HAV) antibodies (immunoglobulin M \[IgM\]), 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 tested positive for coronavirus (SARS-CoV-2) infection without any clinical signs or symptoms within 2 weeks prior to randomization at baseline and/or has had clinical signs and symptoms consistent with coronavirus (SARS-CoV-2) infection and fully recovered within 4 weeks 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.