Duchenne Muscular Dystrophy
Conditions
Brief summary
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
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.
Interventions
DRUGTAS-205
2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal
DRUGPlacebo
1 group: Placebo group. Oral administration for 24 weeks, BID after meal
Sponsors
Taiho Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
5 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to 24 Weeks in the 6-minute Walk Distance (6MWD) | baseline, 24 weeks | The distance the subject can walk as fast as possible in 6 minutes will be evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Time to Rise From the Floor | baseline, and 24 weeks | The time required for the subject to rise from a supine position on the floor as quickly as possible will be evaluated. |
| Mean Change From Baseline in Time to Walk/Run for 10meters | baseline, and 24 weeks | 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. |
| Mean Change From Baseline in Time to up and go (TUG) | baseline, and 24 weeks | This test will assess the extent of the subject's composite mobility, including standing up, walking, repositioning the body, and balancing. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TAS-205（Low Dose Group） TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal | 11 |
| TAS-205（High Dose Group） TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal | 11 |
| Placebo Placebo: 1 group: Placebo group. Oral administration for 24 weeks, BID after meal | 10 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | TAS-205（Low Dose Group） | TAS-205（High Dose Group） | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 11 Participants | 11 Participants | 10 Participants | 32 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 11 Participants | 10 Participants | 32 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 11 participants | 11 participants | 10 participants | 32 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 11 Participants | 11 Participants | 10 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 9 / 11 | 9 / 12 | 10 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 | 0 / 12 |
Outcome results
Primary
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.
Time frame: baseline, 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAS-205（Low Dose Group） | Mean Change From Baseline to 24 Weeks in the 6-minute Walk Distance (6MWD) | -3.5 meter | Standard Deviation 67.3 |
| TAS-205（High Dose Group） | Mean Change From Baseline to 24 Weeks in the 6-minute Walk Distance (6MWD) | -7.5 meter | Standard Deviation 37.3 |
| Placebo | Mean Change From Baseline to 24 Weeks in the 6-minute Walk Distance (6MWD) | -17.0 meter | Standard Deviation 55.6 |
Secondary
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.
Time frame: baseline, and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAS-205（Low Dose Group） | Mean Change From Baseline in Time to Rise From the Floor | 4.011 second | Standard Deviation 6.209 |
| TAS-205（High Dose Group） | Mean Change From Baseline in Time to Rise From the Floor | 1.283 second | Standard Deviation 2.547 |
| Placebo | Mean Change From Baseline in Time to Rise From the Floor | 2.633 second | Standard Deviation 4.246 |
p-value: 0.59695% CI: [-6.757, 4]t-test, 2 sided
p-value: 0.43395% CI: [-2.22, 4.918]t-test, 2 sided
Secondary
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.
Time frame: baseline, and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAS-205（Low Dose Group） | Mean Change From Baseline in Time to up and go (TUG) | 0.594 second | Standard Deviation 2.156 |
| TAS-205（High Dose Group） | Mean Change From Baseline in Time to up and go (TUG) | 0.286 second | Standard Deviation 1.626 |
| Placebo | Mean Change From Baseline in Time to up and go (TUG) | 0.061 second | Standard Deviation 1.626 |
p-value: 0.54995% CI: [-2.363, 1.298]t-test, 2 sided
p-value: 0.76795% CI: [-1.801, 1.351]t-test, 2 sided
Secondary
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.
Time frame: baseline, and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAS-205（Low Dose Group） | Mean Change From Baseline in Time to Walk/Run for 10meters | 1.113 second | Standard Deviation 1.14 |
| TAS-205（High Dose Group） | Mean Change From Baseline in Time to Walk/Run for 10meters | 1.025 second | Standard Deviation 1.296 |
| Placebo | Mean Change From Baseline in Time to Walk/Run for 10meters | 0.629 second | Standard Deviation 1.272 |
p-value: 0.38295% CI: [-1.618, 0.65]t-test, 2 sided
p-value: 0.50195% CI: [-1.61, 0.817]t-test, 2 sided