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

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)

The primary purpose of this study is to evaluate the safety and tolerability of ASP0367.

This study will also evaluate the pharmacokinetics, pharmacodynamics and efficacy on muscle function of ASP0367.

This study is comprised of a 4-week pre-treatment screening period, 24-week treatment period and 4-week post-treatment follow-up period. The 24-week treatment period consists of a 12-week double-blind (DB) part and 12-week open-label extension (OLE) part and each part includes a 2 week Low dose Period and a 10-week High-dose Period.

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.