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

NCT04184882 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 0367-CL-0102
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Duchenne Muscular Dystrophy (DMD)

Keywords

tolerability; ASP0367; MA-0211; safety

Outcome Measures

Primary Outcomes (8)

• Number of participants with Treatment Emergent Adverse Events (TEAEs)

  An AE is any untoward medical occurrence in a subject administered an investigational product (IP), and which does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an AE observed after starting administration of the investigational product (IP) to 28 days after the last dose of IP for the double blind part or moving to the open-label extension part, whichever comes first. An IP-related TEAE is defined as any TEAE with a causal relationship of "yes" by the investigator.

  Up to Week 28

• Number of participants with vital sign abnormalities and/or AEs

  Number of participants with potentially clinically significant vital sign values.

  Up to Week 28

• Number of participants with body weight change abnormalities and/or AEs

  Number of participants with potentially clinically significant body weight.

  Up to Week 28

• Number of participants with electrocardiogram (ECG) abnormalities

  Number of participants with potentially clinically significant 12-ECG values.

  Up to Week 28

• Number of participants with echocardiography abnormalities and/or AEs

  Number of participants with potentially clinically significant echocardiography values.

  Up to Week 28

• Number of participants with laboratory value abnormalities and/or AEs

  Number of participants with potentially clinically significant laboratory values.

  Up to Week 28

• Number of participants with suicidal ideation and/or behavior as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)

  The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinician administered assessment tool that evaluates suicidal ideation and behavior. Number of participants that have an affirmative response provided to the 5 items for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods (not plan) without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 6 items for suicidal behavior (1. Actual attempt, 2. Interrupted attempt, 3. Aborted attempt, 4. Preparatory acts or behavior, 5. Suicidal Behavior 6. Completed suicide,) will be reported.

  Baseline and up to Week 28

• Change from baseline in digit span test

  The Digit span test is a subtest of Wechsler Intelligence Scale for children (WISC). This test comprises 3 parts on the fifth edition (WISC-V). Digit Span Forward requires the subject to repeat numbers in the same order as presented by the interviewer. Digit Span Backward requires the subject to repeat the numbers in the reverse order of that presented by the interviewer. Digit Span Sequencing requires the subject to sequentially order the numbers presented by the interviewer. Scores of this test are based on each raw score and total raw score.

  Baseline and up to Week 24

Secondary Outcomes (10)

• Pharmacokinetics (PK) of ASP0367 in plasma: AUC from the time of dosing to the start of next dosing interval (AUCtau)

  Up to Week 2

• PK of ASP0367 in plasma: maximum concentration (Cmax)

  Up to Week 2

• Pharmacodynamics (PD) of ASP0367: Percent change from baseline in peroxisome proliferator-activated receptor (PPAR) delta target genes expression levels in blood

  Baseline and up to Week 4

• PD of ASP0367: Percent change from baseline in serum myostatin/follistatin ratio

  Baseline and up to Week 12

• Change from baseline in Performance of Upper Limb Module (PUL) (v2.0) assessment score

  Baseline and up to Week 12

Study Arms (2)

ASP0367 group

EXPERIMENTAL

Participants will be dosed investigational product (IP) at the low dose for 2 weeks and then at the high dose for 10 weeks with the total duration of 12 weeks in the DB part and OLE part, respectively.

Drug: Bocidelpar

Placebo to ASP0367 group

PLACEBO COMPARATOR

Participants will be dosed matching placebo in the DB part. In OLE part, participants will dosed IP at the low dose for 2 weeks and then at the high dose for 10 weeks with the total duration of 12 weeks.

Drug: Bocidelpar; Drug: Placebo

Interventions

Bocidelpar DRUG

Oral

Also known as: MA-0211, ASP0367

ASP0367 group; Placebo to ASP0367 group

Placebo DRUG

Oral

Placebo to ASP0367 group

Eligibility Criteria

• Age: 8 Years - 16 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (5)

University of California Davis Health

Sacramento, California, 95817, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21201, United States

Location

UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Children's Hospital of Richmond at VCU

Richmond, Virginia, 23219, United States

Location

Related Links

• Link to plain language summary of the study on the Trial Results Summaries website.
• Link to results and other applicable study documents on the Astellas Clinical Trials website.

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Associate Director

  Astellas Pharma Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2019
• First Posted: December 4, 2019
• Study Start: February 24, 2021
• Primary Completion: September 4, 2022
• Study Completion: September 4, 2022
• Last Updated: October 22, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)