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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
8
Oral
Oral
University of California Davis Health
Sacramento, California, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
Kennedy Krieger Institute
Baltimore, Maryland, United States
UMass Memorial Medical Center
Worcester, Massachusetts, United States
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.
Time frame: Up to Week 28
Number of participants with vital sign abnormalities and/or AEs
Number of participants with potentially clinically significant vital sign values.
Time frame: Up to Week 28
Number of participants with body weight change abnormalities and/or AEs
Number of participants with potentially clinically significant body weight.
Time frame: Up to Week 28
Number of participants with electrocardiogram (ECG) abnormalities
Number of participants with potentially clinically significant 12-ECG values.
Time frame: Up to Week 28
Number of participants with echocardiography abnormalities and/or AEs
Number of participants with potentially clinically significant echocardiography values.
Time frame: Up to Week 28
Number of participants with laboratory value abnormalities and/or AEs
Number of participants with potentially clinically significant laboratory values.
Time frame: 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)
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Children's Hospital of Richmond at VCU
Richmond, Virginia, United States
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.
Time frame: 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.
Time frame: Baseline and up to Week 24
Pharmacokinetics (PK) of ASP0367 in plasma: AUC from the time of dosing to the start of next dosing interval (AUCtau)
AUCtau will be recorded from the PK plasma samples collected.
Time frame: Up to Week 2
PK of ASP0367 in plasma: maximum concentration (Cmax)
Cmax will be recorded from the PK plasma samples collected.
Time frame: 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
Whole blood cell samples will be collected to measure percent change in target gene expressions.
Time frame: Baseline and up to Week 4
PD of ASP0367: Percent change from baseline in serum myostatin/follistatin ratio
Serum samples will be collected to record myostatin.
Time frame: Baseline and up to Week 12
Change from baseline in Performance of Upper Limb Module (PUL) (v2.0) assessment score
The PUL Assessment v2.0 includes a total of 23 upper limb test items, with the first entry item A used to define the starting functional level. The remaining 22 items are subdivided into 3 major dimension levels as following; shoulder level (6 items, maximum score of 12), elbow level (9 items, maximum score of 17) and distal level dimension (7 items, maximum score of 13). Positive change in scores indicates an improvement.
Time frame: Baseline and up to Week 12
Change from baseline on Pediatric Quality of Life (PedsQL) Multidimensional Fatigue Scale
PedsQL Multidimensional Fatigue Scale comprises the General Fatigue Scale (6 items), Sleep/Rest Fatigue Scale (6 items) and Cognitive Fatigue Scale (6 items). A 5-point response scale in each item is utilized (0 never a problem; 1 almost never a problem; 2 sometimes a problem; 3 often a problem; 4 almost always a problem). Negative change in scores indicates an improvement. This scale is based on the subject's age and will be assessed by both subject and parent or legal guardian.
Time frame: Baseline and up to Week 12
Change from baseline in distance walked in 2 minutes assessed in meters
The 2-minute walk test (2MWT) is a measurement of endurance that assesses walking distance over 2 minutes. Only ambulatory subjects conduct the 2MWT in this study.
Time frame: Baseline and up to Week 12
Percent change from baseline in the assisted 6 minute cycling test (a6MCT) maximal attained revolutions
The a6MCT has been developed as a submaximal endurance test for both legs (leg-cycling) and arms (arm-cranking) for children who are expected to lose their walking ability in the near future or are wheel chair dependent. Only arm-cranking will be applied to this study.
Time frame: Baseline and up to Week 12
Change from baseline in the a6MCT maximal attained revolutions
The a6MCT has been developed as a submaximal endurance test for both legs (leg-cycling) and arms (arm-cranking) for children who are expected to lose their walking ability in the near future or are wheel chair dependent. Only arm-cranking will be applied to this study.
Time frame: Baseline and up to Week 12
Change from baseline in fat fraction by magnetic resonance spectroscopy (MRS)
The fat fraction by MRS will be assessed for the vastus lateralis (VL) and soleus (SOL) muscles.
Time frame: Baseline, Week 12 and Week 24