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

• Sponsor: Taiho Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02752048
• Collaborator: (none)
• Enrollment: 36
• Locations: 11
• Arms: 3
• Duration (Months): 17.5
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy	Drug: TAS-205; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase IIa Study of TAS-205 in Patients With Duchenne Muscular Dystrophy
• Study Start Date: May 1, 2016
• Actual Primary Completion Date: May 15, 2017
• Actual Study Completion Date: Oct 17, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAS-205（Low dose group） 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; 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal
Experimental: TAS-205（High dose group） 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; 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal
Placebo Comparator: Placebo Placebo group: Oral administration of tablets for 24 weeks, BID after meal	Drug: Placebo; 1 group: Placebo group. Oral administration for 24 weeks, BID after meal

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years and Older
• Sexes Eligible for Study: Male
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nagoya City University Hospital	Aichi		Japan	467-8601
2	National Hospital Organization Nagara Medical Center	Gifu		Japan	502-8558
3	Kobe University Hospital	Hyogo		Japan	650-0017
4	National Hospital Organization Utano Hospital	Kyoto		Japan	616-8255
5	Shinshu University Hospital	Nagano		Japan	390-8621
6	National Hospital Organization Niigata National Hospital	Niigata		Japan	945-8585
7	National Hospital Organization Toneyama National Hospital	Osaka		Japan	560-8552
8	National Hospital Organization Higashisaitama Hospital	Saitama		Japan	349-0196
9	Tokyo Women's Medical University Hospital	Tokyo		Japan	162-8666
10	National Center of Neurology and Psychiatry	Tokyo		Japan	187-8551
11	Tottori University Hospital	Tottori		Japan	683-8504

Sponsors and Collaborators

• Taiho Pharmaceutical Co., Ltd.

Investigators

• Study Director: Taiho Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd.

Study Documents (Full-Text)

• Study Protocol - Apr 7, 2016
• Statistical Analysis Plan - Aug 14, 2018

More Information

Publications

None provided.

• Responsible Party: Taiho Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT02752048
• Other Study ID Numbers: Taiho10053040
• First Posted: Apr 26, 2016
• Last Update Posted: Apr 20, 2020
• Last Verified: Mar 1, 2020

• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne

Study Results

Participant Flow

Arm/Group Title	TAS-205（Low Dose Group）	TAS-205（High Dose Group）	Placebo
Arm/Group Description	TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal	TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal	Placebo: 1 group: Placebo group. Oral administration for 24 weeks, BID after meal
Period Title: Overall Study
STARTED	11	12	13
COMPLETED	11	12	10
NOT COMPLETED	0	0	3

Baseline Characteristics

Arm/Group Title	TAS-205（Low Dose Group）	TAS-205（High Dose Group）	Placebo	Total
Arm/Group Description	TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal	TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal	Placebo: 1 group: Placebo group. Oral administration for 24 weeks, BID after meal	Total of all reporting groups
Overall Participants	11	11	10	32
Age (Count of Participants)
<=18 years	11 100%	11 100%	10 100%	32 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	11 100%	11 100%	10 100%	32 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	11 100%	11 100%	10 100%	32 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Japan	11 100%	11 100%	10 100%	32 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TAS-205（Low Dose Group）	TAS-205（High Dose Group）	Placebo
Arm/Group Description	TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal	TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal	Placebo: 1 group: Placebo group. Oral administration for 24 weeks, BID after meal
Measure Participants	11	11	10
Mean (Standard Deviation) [meter]	-3.5 (67.3)	-7.5 (37.3)	-17.0 (55.6)

2. Secondary Outcome

Title	Mean Change From Baseline in Time to Rise From the Floor
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TAS-205（Low Dose Group）	TAS-205（High Dose Group）	Placebo
Arm/Group Description	TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal	TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal	Placebo: 1 group: Placebo group. Oral administration for 24 weeks, BID after meal
Measure Participants	11	11	10
Mean (Standard Deviation) [second]	4.011 (6.209)	1.283 (2.547)	2.633 (4.246)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAS-205（Low Dose Group）, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Change in time to rise from the floor from baseline to Week 24 were calculated to evaluate
Statistical Test of Hypothesis	p-Value	0.596
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.378
	Confidence Interval	(2-Sided) 95%; -6.757 to 4.000
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TAS-205（High Dose Group）, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Change in time to rise from the floor from baseline to Week 24 were calculated to evaluate
Statistical Test of Hypothesis	p-Value	0.433
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.349
	Confidence Interval	(2-Sided) 95%; -2.220 to 4.918
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Mean Change From Baseline in Time to Walk/Run for 10meters
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TAS-205（Low Dose Group）	TAS-205（High Dose Group）	Placebo
Arm/Group Description	TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal	TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal	Placebo: 1 group: Placebo group. Oral administration for 24 weeks, BID after meal
Measure Participants	11	11	10
Mean (Standard Deviation) [second]	1.113 (1.140)	1.025 (1.296)	0.629 (1.272)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAS-205（Low Dose Group）, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Change in 10-m walk/run test from baseline to Week 24 were calculated to evaluate
Statistical Test of Hypothesis	p-Value	0.382
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.484
	Confidence Interval	(2-Sided) 95%; -1.618 to 0.650
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TAS-205（High Dose Group）, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Change in 10-m walk/run test from baseline to Week 24 were calculated to evaluate
Statistical Test of Hypothesis	p-Value	0.501
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.397
	Confidence Interval	(2-Sided) 95%; -1.610 to 0.817
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Mean Change From Baseline in Time to up and go (TUG)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TAS-205（Low Dose Group）	TAS-205（High Dose Group）	Placebo
Arm/Group Description	TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal	TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal	Placebo: 1 group: Placebo group. Oral administration for 24 weeks, BID after meal
Measure Participants	11	11	10
Mean (Standard Deviation) [second]	0.594 (2.156)	0.286 (1.626)	0.061 (1.626)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAS-205（Low Dose Group）, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Change in time to up and go from baseline to Week 24 were calculated to evaluate
Statistical Test of Hypothesis	p-Value	0.549
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.533
	Confidence Interval	(2-Sided) 95%; -2.363 to 1.298
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TAS-205（High Dose Group）, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Change in time to up and go from baseline to Week 24 were calculated to evaluate
Statistical Test of Hypothesis	p-Value	0.767
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.225
	Confidence Interval	(2-Sided) 95%; -1.801 to 1.351
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From registration point to the end of follow-up period which was after four weeks from the end of 24-weeks administration
Arm/Group Title	TAS-205（Low Dose Group）		TAS-205（High Dose Group）		Placebo
Arm/Group Description	TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal		TAS-205: 2 groups: Low dose group, High dose group. Oral administration for 24 weeks, bis in die (BID) after meal		Placebo: 1 group: Placebo group. Oral administration for 24 weeks, BID after meal
All Cause Mortality
	TAS-205（Low Dose Group）		TAS-205（High Dose Group）		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/12 (0%)		0/12 (0%)
Serious Adverse Events
	TAS-205（Low Dose Group）		TAS-205（High Dose Group）		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	TAS-205（Low Dose Group）		TAS-205（High Dose Group）		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/11 (81.8%)		9/12 (75%)		10/12 (83.3%)
Blood and lymphatic system disorders
Lymphadenopathy	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Cardiac disorders
Constipation	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Dental caries	0/11 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Diarrhoea	1/11 (9.1%)	1	1/12 (8.3%)	1	0/12 (0%)	0
Stomatitis	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
General disorders
Mucosal inflammation	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Pyrexia	0/11 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Peripheral swelling	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Infections and infestations
Bronchitis	1/11 (9.1%)	1	1/12 (8.3%)	1	2/12 (16.7%)	2
Gastroenteritis	2/11 (18.2%)	2	3/12 (25%)	3	0/12 (0%)	0
Herpes zoster	0/11 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Impetigo	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Influenza	0/11 (0%)	0	0/12 (0%)	0	2/12 (16.7%)	2
Mumps	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Pneumonia mycoplasmal	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Rhinitis	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Sinusitis	1/11 (9.1%)	1	0/12 (0%)	0	0/12 (0%)	0
Tonsillitis	1/11 (9.1%)	1	0/12 (0%)	0	0/12 (0%)	0
Upper respiratory tract infection	1/11 (9.1%)	1	2/12 (16.7%)	2	1/12 (8.3%)	1
Viral upper respiratory tract infection	0/11 (0%)	0	1/12 (8.3%)	1	1/12 (8.3%)	1
Beta haemolytic streptococcal infection	1/11 (9.1%)	1	0/12 (0%)	0	0/12 (0%)	0
Pneumonia bacterial	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Injury, poisoning and procedural complications
Chillblains	0/11 (0%)	0	0/12 (0%)	0	2/12 (16.7%)	2
Excoriation	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Investigations
Blood corticotrophin decreased	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Cortisol decreased	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Glucose urine present	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Muscle enzyme increased	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Cystatin C increased	1/11 (9.1%)	1	0/12 (0%)	0	0/12 (0%)	0
Urobilinogen urine increased	0/11 (0%)	0	2/12 (16.7%)	2	0/12 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/11 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/11 (9.1%)	1	1/12 (8.3%)	1	2/12 (16.7%)	2
Muscle spasms	1/11 (9.1%)	1	0/12 (0%)	0	0/12 (0%)	0
Myalgia	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Pain in extremity	2/11 (18.2%)	2	1/12 (8.3%)	1	2/12 (16.7%)	2
Nervous system disorders
Headache	1/11 (9.1%)	1	0/12 (0%)	0	0/12 (0%)	0
Vomiting psychogenic	0/11 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Psychiatric disorders
Head banging	0/11 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Cough	0/11 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Epistaxis	0/11 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Rhinorrhoea	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Upper respiratory tract inflammation	2/11 (18.2%)	2	3/12 (25%)	3	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Dyshidrotic eczema	1/11 (9.1%)	1	0/12 (0%)	0	0/12 (0%)	0
Eczema asteatotic	0/11 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Erythema	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Leukoderma	1/11 (9.1%)	1	0/12 (0%)	0	0/12 (0%)	0
Palmar erythema	1/11 (9.1%)	1	0/12 (0%)	0	0/12 (0%)	0
Papule	0/11 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Rash	1/11 (9.1%)	1	1/12 (8.3%)	1	1/12 (8.3%)	1
Rash erythematous	0/11 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Urticaria	2/11 (18.2%)	2	1/12 (8.3%)	1	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.