A Phase IIa Study of TAS-205 for Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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The objective of this study is to evaluate the efficacy after 24-week repeated oral doses of TAS-205 in patients with Duchenne Muscular Dystrophy (DMD) in an exploratory manner.

Detailed Description
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Duchenne Muscular Dystrophy (DMD) is the most common fatal genetic disorder diagnosed in childhood, affecting approximately 1 in 3,500 lives male births. DMD patients suffer from a relentless decline in muscle strength that impairs the ability of walking and breathing, resulting in their lives with wheelchairs and then loss of upper body function. The main objective of this study is to evaluate the efficacy after 24-week repeated oral doses of TAS-205 in patients with DMD in an exploratory manner. The objective of this study is also to evaluate the safety, the dose-response and the urinary excretion of pharmacodynamic (PD) marker after 24-week repeated oral doses of TAS-205 in DMD patients.

Official Title
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A Randomized Phase IIa Study of TAS-205 in Patients With Duchenne Muscular Dystrophy

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: TAS-205
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to give an informed consent. If applicable, able to give an informed assent. Phenotypic evidence of DMD. Male and ≧5 years of age. Bodyweight ≧7.5 kg and <60 kg. Able to complete the 6MWD test with a distance of at least 75 m. Able to take tablets. If taking oral glucocorticoids no significant change in the total daily or dosing 6 months before enrollment. Exclusion Criteria: Any serious drug allergy. A forced vital capacity (FVC) of <50% of predicted value. Wearing a respirator continuously (except for the use during sleep). A left ventricular ejection fraction (EF) of <40% or fractional shortening (FS) of <25% on echocardiogram. Clinically significant cardiac failure and respiratory failure. Ongoing immunosuppressive therapy (other than corticosteroids) . Surgical history or plan for surgery that may affect muscular strength or motor function. Any injury that may affect muscular strength or motor function. With any systemic allergic disease or any chronic inflammatory disease. Previous gene therapy (exon skipping, or stop codon read through therapy), cell-based therapy, or any other investigational agents.

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAS-205（Low dose group）<br>Low dose group：Oral administration of tablets for 24 weeks, bis in die (BID) after meal The number of tablets of the study drug corresponding to the dosage (6.67-13.33 mg/kg/dose) by body weight within 14 days before enrollment was to be administered within 30 minutes after breakfast and dinner. | Drug: TAS-205<br>* 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal<br>|
| Experimental: TAS-205（High dose group）<br>High dose group: Oral administration of tablets for 24 weeks, bis in die (BID) after meal The number of tablets of the study drug corresponding to the dosage (13.33-26.67 mg/kg/dose) by body weight within 14 days before enrollment was to be administered within 30 minutes after breakfast and dinner. | Drug: TAS-205<br>* 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal<br>|
| Placebo Comparator: Placebo<br>Placebo group: Oral administration of tablets for 24 weeks, BID after meal | Drug: Placebo<br>* 1 group: Placebo group. Oral administration for 24 weeks, BID after meal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to 24 Weeks in the 6-minute Walk Distance (6MWD) | The distance the subject can walk as fast as possible in 6 minutes will be evaluated. | baseline, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Time to Rise From the Floor | The time required for the subject to rise from a supine position on the floor as quickly as possible will be evaluated. | baseline, and 24 weeks | 
| Mean Change From Baseline in Time to Walk/Run for 10meters | The time required for the subject to run or walk as quickly as possible a 10 m-wide passage with marks affixed on the floor will be evaluated. | baseline, and 24 weeks | 
| Mean Change From Baseline in Time to up and go (TUG) | This test will assess the extent of the subject's composite mobility, including standing up, walking, repositioning the body, and balancing. | baseline, and 24 weeks |