Clinical Study of TA-650 in Patients With Behcet's Disease (BD) With Special Lesions

• Sponsor: Mitsubishi Tanabe Pharma Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01532570
• Collaborator: (none)
• Enrollment: 18
• Locations: 6
• Arm: 1
• Duration (Months): 28
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of TA-650 in patients with Behcet's disease ( BD ) with special lesions after the administration of TA-650 at a dosage of 5 mg/kg in weeks 0, 2, and 6, then every 8 weeks after week 14 up to week 46.

Condition or Disease	Intervention/Treatment	Phase
Behcet's Disease; Behcet Syndrome; Neuro-Behcet's Disease	Drug: TA-650	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: To Evaluate the Efficacy, Safety, and Pharmacokinetics of TA-650 in Patients With Behcet's Disease ( BD ) With Special Lesions After the Administration of TA-650
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TA-650	Drug: TA-650; TA-650 will be intravenously infused at a dosage of 5 mg/kg slowly over a period of more than 2 hours at the first administration (weeks 0), 2, and 6, and then every 8 weeks up to week 46. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Complete Response at Week 30 [Week 30]

   We defined the patient who met the following criteria as the complete responders. The criteria of complete responders are that clinical symptoms associated with each BD have disappeared and morphological characteristics (ex. ulcers area, Computed tomography (CT) or Positron emission tomography/Computed tomography (PET/CT) findings etc) at the lesion site and inflammatory markers (ex. cerebrospinal fluid and serum inflammatory markers) are improved compared to Week 0.

Secondary Outcome Measures

1. Percentage of Participants With Complete Response at Week 14 and 54 [Week 14, Week 54]

   We defined the patient who met the following criteria as the complete responders. The criteria of complete responders are that clinical symptoms associated with each BD have disappeared and morphological characteristics (ex. ulcers area, CT or PET/CT findings etc) at the lesion site and inflammatory markers (ex. cerebrospinal fluid and serum inflammatory markers) are improved compared to Week 0.

2. Patient General Visual Analogue Scale (VAS) for the Clinical Symptoms Associated With Each BD [Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54]

   The VAS evaluation measured using the "General VAS evaluation From" and the range is from 0 to 100 mm. The best condition per one week before evaluation visit for the clinical symptoms associated with each BD is defined as "0" and the worst condition is defined as "100". The time of final evaluation : Final time point for the 5 mg/kg patients, final time point during administration of 5 mg/kg for the 10 mg/kg patients, final time point during administration of 5 mg/kg for patients who discontinued the study.

3. Imaging Findings:Endoscopic Examination for Intestinal BD [Week 14, Week 30, Week 54]

   The investigator assessed the length of the major axis of the principal intestinal ulcer at day of evaluation and scored in accordance with the following categories, "Healed/scarred, Reduced to =< 25%, Reduced to > 25% to =< 50% or Reduced to > 50%/no change/increased" in the principal intestinal ulcer compared to size at Week 0.

4. Imaging Findings: Brain Magnetic Resonance Imaging (MRI) for Acute Neuro-BD [Week 14, Week 30, Week 54]

   Changes in brain MRI findings were scored at day of evaluation, in accordance with the following categories, "No high-intensity areas, Reduction or No changes/increase" in the size of high-intensity areas compared to Week 0.

5. Imaging Findings: Brainstem MRI for Chronic Neuro-BD [Week 14, Week 30, Week 54]

   Changes in brainstem MRI findings were scored at day of evaluation, in accordance with the following categories, "Unchanged or Reduced" in the brainstem area compared to Week 0.

6. Imaging Findings: CT, PET/CT for Vascular-BD [Week 14, Week 30, Week 54]

   Changes in CT or PET/CT findings were scored at day of evaluation, in accordance with the following categories, "Improves, Unchanged or Worsened" by comparison with those at Week 0.

7. Concentration of Inflammatory Biomarker (C-reactive Protein (CRP)) of Intestinal BD [Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54]

   The time of final evaluation : Final time point for the 5 mg/kg patients, final time point during administration of 5 mg/kg for the 10 mg/kg patients, final time point during administration of 5 mg/kg for patients who discontinued the study.

8. Concentration of Inflammatory Biomarker (CRP) of Vascular BD [Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54]

   The time of final evaluation : Final time point for the 5 mg/kg patients, final time point during administration of 5 mg/kg for the 10 mg/kg patients, final time point during administration of 5 mg/kg for patients who discontinued the study.

9. Level of Inflammatory Biomarker (Erythrocyte Sedimentation Rate) of Vascular BD [Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54]

   The time of final evaluation : Final time point for the 5 mg/kg patients, final time point during administration of 5 mg/kg for the 10 mg/kg patients, final time point during administration of 5 mg/kg for patients who discontinued the study.

10. Cell Counts in Cerebrospinal Fluid (CSF) for Acute Neuro-BD [Week 0, Week 14, Week 30, Week 54]

    The time of final evaluation : Final time point for the 5 mg/kg patients, final time point during administration of 5 mg/kg for the 10 mg/kg patients, final time point during administration of 5 mg/kg for patients who discontinued the study.

11. Interleukin-6 (IL-6) Concentration in CSF for Neuro-BD [Week 0, Week 14, Week 30, Week 54]

12. The Number of Improved Intestinal BD Patients From Baseline [Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54]

    The investigator assessed clinical symptoms associated with intestinal BD in one week before the day of evaluation as " No symptom, Very slightly poor, Slightly poor, Poor or Extremely poor". We calculated improved patients in comparison with those for Week 0.

13. Change From Baseline in Clinical Symptoms Associated With Neuro-BD Patients [Week 2, 6, 10, then every 4 weeks after Week 14 to Week 54]

    The investigator assessed the clinical symptoms associated with neuro-BD at each time point of the evaluation in compared to Week 0, in accordance with the categories as "No symptom, Improved, Unchanged or Worsened".

14. Change From Baseline in Clinical Symptoms Associated With Vascular BD Patients [Week 2, 6, 10, then every 4 weeks after Week 14 to Week 54]

    The investigator assessed the clinical symptoms associated with vascular-BD at each time point of the evaluation in compared to Week 0, in accordance with the categories as "No symptom, Improved, Unchanged or Worsened".

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who were diagnosed with the complete or incomplete type of Behcet's disease according to "The criteria for a diagnosis of Behcet's disease, Ministry of Health, Labour and Welfare in Japan (partially revised in 2010)"

• Patients who have special lesions despite having received conventional treatments for special lesions, or patients who cannot receive conventional treatments due to intolerability.

• Patients who have clinical symptoms associated with each special lesions.

Exclusion Criteria:

• Patients with intestinal, neuro-, vascular Behcet's disease in whom a differential diagnosis of each Behcet's disease from other conditions．

• Patients who have received treatment with infliximab within 1 year before enrollment for another purpose than treating special lesions; or patients whose previous treatment with infliximab was discontinued due to adverse events.

• Patients who had participated in another clinical study and had received a study drug within 12 weeks before giving acquirement.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational site	Chubu		Japan
2	Investigational site	Hokkaido		Japan
3	Investigational site	Kanto		Japan
4	Investigational site	Kinki		Japan
5	Investigational site	Kyusyu		Japan
6	Investigational site	Tohoku		Japan

Sponsors and Collaborators

• Mitsubishi Tanabe Pharma Corporation

Investigators

• Study Director: Yoshiaki Ishigatsubo, MD, Ph.D, Yokohama City University Graduate School of Medicine
• Study Director: Toshifumi Hibi, MD, Kitasato University Kitasato Institute Hospital
• Study Director: Shunsei Hirohata, MD, Kitasato University School of Medicine
• Study Director: Kazuoki Kondo, MD, Mitsubihsi Tanabe Pharma Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mitsubishi Tanabe Pharma Corporation
• ClinicalTrials.gov Identifier: NCT01532570
• Other Study ID Numbers: TA-650-23
• First Posted: Feb 14, 2012
• Last Update Posted: Dec 16, 2016
• Last Verified: Oct 1, 2016

• Keywords provided by Mitsubishi Tanabe Pharma Corporation: Behcet's disease; intestinal Behcet's disease; neuro-Behcet's disease; vascular Behcet's disease
• Additional relevant MeSH terms: Behcet Syndrome

Study Results

Participant Flow

Arm/Group Title	Intestinal BD	Acute Neuro-BD	Chronic Progressive Neuro-BD	Vascular BD
Arm/Group Description	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.
Period Title: Overall Study
STARTED	11	2	1	4
COMPLETED	10	1	1	4
NOT COMPLETED	1	1	0	0

Baseline Characteristics

Arm/Group Title	Intestinal BD	Acute Neuro-BD	Chronic Progressive Neuro-BD	Vascular BD	Total
Arm/Group Description	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	Total of all reporting groups
Overall Participants	11	2	1	4	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.0 (13.4)	34.0 (5.7)	47.0 (NA)	44.0 (2.9)	37.6 (11.4)
Gender (Count of Participants)
Female	6 54.5%	1 50%	0 0%	1 25%	8 44.4%
Male	5 45.5%	1 50%	1 100%	3 75%	10 55.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Complete Response at Week 30
Description	We defined the patient who met the following criteria as the complete responders. The criteria of complete responders are that clinical symptoms associated with each BD have disappeared and morphological characteristics (ex. ulcers area, Computed tomography (CT) or Positron emission tomography/Computed tomography (PET/CT) findings etc) at the lesion site and inflammatory markers (ex. cerebrospinal fluid and serum inflammatory markers) are improved compared to Week 0.
Time Frame	Week 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intestinal BD	Acute Neuro-BD	Chronic Progressive Neuro-BD	Vascular BD
Arm/Group Description	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.
Measure Participants	11	2	1	4
Number [percentage of Complete Responders]	54.5	0	100	100

2. Secondary Outcome

Title	Percentage of Participants With Complete Response at Week 14 and 54
Description	We defined the patient who met the following criteria as the complete responders. The criteria of complete responders are that clinical symptoms associated with each BD have disappeared and morphological characteristics (ex. ulcers area, CT or PET/CT findings etc) at the lesion site and inflammatory markers (ex. cerebrospinal fluid and serum inflammatory markers) are improved compared to Week 0.
Time Frame	Week 14, Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intestinal BD	Acute Neuro-BD	Chronic Progressive Neuro-BD	Vascular BD
Arm/Group Description	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.
Measure Participants	11	2	1	4
Week 14 (n=11, 2, 1, 4)	54.5	0	100	100
Week 54 (n=10, 1, 1, 4)	60	0	100	100

3. Secondary Outcome

Title	Patient General Visual Analogue Scale (VAS) for the Clinical Symptoms Associated With Each BD
Description	The VAS evaluation measured using the "General VAS evaluation From" and the range is from 0 to 100 mm. The best condition per one week before evaluation visit for the clinical symptoms associated with each BD is defined as "0" and the worst condition is defined as "100". The time of final evaluation : Final time point for the 5 mg/kg patients, final time point during administration of 5 mg/kg for the 10 mg/kg patients, final time point during administration of 5 mg/kg for patients who discontinued the study.
Time Frame	Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intestinal BD	Neuro-BD (Acute+Chronic Progressive)	Vascular BD
Arm/Group Description	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	Acute; A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30. Chronic Progressive; A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.
Measure Participants	11	3	4
Week 0 (n=11, 3, 4)	55.5 (22.9)	41.3 (11.0)	40.5 (34.4)
Week 2 (n=11, 3, 4)	42.7 (30.9)	33.0 (23.1)	11.8 (7.8)
Week 6 (n=11, 3, 4)	26.4 (20.3)	15.0 (17.1)	14.3 (8.1)
Week 10 (n=11, 3, 4)	23.6 (19.8)	23.0 (20.4)	17.8 (14.0)
Week 14 (n=11, 3, 4)	32.4 (24.0)	28.3 (30.0)	13.5 (9.8)
Week 18 (n=11, 3, 4)	23.9 (20.8)	31.7 (22.4)	15.3 (8.9)
Week 22 (n=11, 3, 4)	31.8 (26.0)	35.3 (31.5)	17.8 (6.4)
Week 26 (n=11, 2, 4)	28.9 (20.7)	18.5 (23.3)	17.5 (9.8)
Week 30 (n=11, 2, 4)	31.1 (29.2)	15.0 (21.2)	11.8 (7.5)
Week 34 (n=11, 2, 4)	21.2 (21.6)	12.5 (17.7)	18.8 (9.2)
Week 38 (n=11, 2, 4)	25.4 (30.8)	11.5 (16.3)	10.3 (8.3)
Week 42 (n=10, 2, 4)	20.9 (20.4)	13.0 (18.4)	13.5 (9.3)
Week 46 (n=10, 2, 4)	22.3 (27.5)	11.5 (16.3)	10.5 (6.6)
Week 50 (n=10, 2, 4)	17.5 (25.1)	11.5 (16.3)	22.8 (25.4)
Week 54 (n=10, 2, 4)	21.0 (26.6)	8.5 (12.0)	11.3 (7.9)
Final (n=11, 3, 4)	26.9 (29.6)	7.7 (8.6)	11.3 (7.9)

4. Secondary Outcome

Title	Imaging Findings:Endoscopic Examination for Intestinal BD
Description	The investigator assessed the length of the major axis of the principal intestinal ulcer at day of evaluation and scored in accordance with the following categories, "Healed/scarred, Reduced to =< 25%, Reduced to > 25% to =< 50% or Reduced to > 50%/no change/increased" in the principal intestinal ulcer compared to size at Week 0.
Time Frame	Week 14, Week 30, Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intestinal BD
Arm/Group Description	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.
Measure Participants	11
The ulcer was cured or scarred: Week 14 (n=11)	9 81.8%
Reduced to = < 1/4: Week 14 (n=11)	0 0%
Reduced to > 1/4 to = < 1/2: Week 14 (n=11)	0 0%
Reduced to > 1/2 or increase: Week 14 (n=11)	2 18.2%
The ulcer was cured or scarred: Week 30 (n=11)	9 81.8%
Reduced to = < 1/4: Week 30 (n=11)	0 0%
Reduced to > 1/4 to = < 1/2: Week 30 (n=11)	0 0%
Reduced to > 1/2 or increase: Week 30 (n=11)	2 18.2%
The ulcer was cured or scarred: Week 54 (n=9)	8 72.7%
Reduced to = < 1/4: Week 54 (n=9)	0 0%
Reduced to > 1/4 to = < 1/2: Week 54 (n=9)	0 0%
Reduced to > 1/2 or increase: Week 54 (n=9)	1 9.1%
The ulcer was cured or scarred: Final (n=11)	9 81.8%
Reduced to = < 1/4: Final (n=11)	0 0%
Reduced to > 1/4 to = < 1/2: Final (n=11)	0 0%
Reduced to > 1/2 or increase: Final (n=11)	2 18.2%

5. Secondary Outcome

Title	Imaging Findings: Brain Magnetic Resonance Imaging (MRI) for Acute Neuro-BD
Description	Changes in brain MRI findings were scored at day of evaluation, in accordance with the following categories, "No high-intensity areas, Reduction or No changes/increase" in the size of high-intensity areas compared to Week 0.
Time Frame	Week 14, Week 30, Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Acute Neuro-BD
Arm/Group Description	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.
Measure Participants	2
Reduced high intensity areas, Week 14 (n=2)	2 18.2%
Reduced high intensity areas, Week 30 (n=1)	1 9.1%
Reduced high intensity areas, Week 54 (n=1)	1 9.1%

6. Secondary Outcome

Title	Imaging Findings: Brainstem MRI for Chronic Neuro-BD
Description	Changes in brainstem MRI findings were scored at day of evaluation, in accordance with the following categories, "Unchanged or Reduced" in the brainstem area compared to Week 0.
Time Frame	Week 14, Week 30, Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chronic Progressive Neuro-BD
Arm/Group Description	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.
Measure Participants	1
Unchanged brain stem area, Week 14	1 9.1%
Unchanged brain stem area, Week 30	1 9.1%
Unchanged brain stem area, Week 54	1 9.1%

7. Secondary Outcome

Title	Imaging Findings: CT, PET/CT for Vascular-BD
Description	Changes in CT or PET/CT findings were scored at day of evaluation, in accordance with the following categories, "Improves, Unchanged or Worsened" by comparison with those at Week 0.
Time Frame	Week 14, Week 30, Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vascular-BD
Arm/Group Description	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.
Measure Participants	4
Improved, Week 14	3 27.3%
Unchanged, Week 14	1 9.1%
Woesened, Week 14	0 0%
Improved, Week 30	3 27.3%
Unchanged, Week 30	1 9.1%
Worsened, Week 30	0 0%
Improved, Week 54	3 27.3%
Unchanged, Week 54	1 9.1%
Worsened, Week 54	0 0%

8. Secondary Outcome

Title	Concentration of Inflammatory Biomarker (C-reactive Protein (CRP)) of Intestinal BD
Description	The time of final evaluation : Final time point for the 5 mg/kg patients, final time point during administration of 5 mg/kg for the 10 mg/kg patients, final time point during administration of 5 mg/kg for patients who discontinued the study.
Time Frame	Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intestinal BD
Arm/Group Description	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.
Measure Participants	11
Week 0 (n=11)	0.20
Week 2 (n=11)	0.00
Week 6 (n=11)	0.10
Week 10 (n=11)	0.10
Week 14 (n=10)	0.15
Week 18 (n=11)	0.10
Week 22 (n=11)	0.10
Week 26 (n=11)	0.00
Week 30 (n=11)	0.10
Week 34 (n=11)	0.00
Week 38 (n=11)	0.10
Week 42 (n=10)	0.00
Week 46 (n=10)	0.00
Week 50 (n=10)	0.05
Week 54 (n=10)	0.10
Final (n=11)	0.10

9. Secondary Outcome

Title	Concentration of Inflammatory Biomarker (CRP) of Vascular BD
Description	The time of final evaluation : Final time point for the 5 mg/kg patients, final time point during administration of 5 mg/kg for the 10 mg/kg patients, final time point during administration of 5 mg/kg for patients who discontinued the study.
Time Frame	Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vascular-BD
Arm/Group Description	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.
Measure Participants	4
Week 0	0.90
Week 2	0.25
Week 6	0.20
Week 10	0.10
Week 14	0.15
Week 18	0.15
Week 22	0.10
Week 26	0.10
Week 30	0.10
Week 34	0.10
Week 38	0.15
Week 42	0.10
Week 46	0.15
Week 50	0.05
Week 54	0.15
Final	0.15

10. Secondary Outcome

Title	Level of Inflammatory Biomarker (Erythrocyte Sedimentation Rate) of Vascular BD
Description	The time of final evaluation : Final time point for the 5 mg/kg patients, final time point during administration of 5 mg/kg for the 10 mg/kg patients, final time point during administration of 5 mg/kg for patients who discontinued the study.
Time Frame	Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vascular-BD
Arm/Group Description	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.
Measure Participants	4
Week 0	31.0
Week 2	11.0
Week 6	8.0
Week 10	7.0
Week 14	8.5
Week 18	6.5
Week 22	5.5
Week 26	7.5
Week 30	4.5
Week 34	6.5
Week 38	9.0
Week 42	9.5
Week 46	8.5
Week 50	8.0
Week 54	6.5
Final	6.5

11. Secondary Outcome

Title	Cell Counts in Cerebrospinal Fluid (CSF) for Acute Neuro-BD
Description	The time of final evaluation : Final time point for the 5 mg/kg patients, final time point during administration of 5 mg/kg for the 10 mg/kg patients, final time point during administration of 5 mg/kg for patients who discontinued the study.
Time Frame	Week 0, Week 14, Week 30, Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Acute Neuro BD (Patient 1)	Acute Neuro-BD (Patient 2)
Arm/Group Description
Measure Participants	1	1
Week 0	37	3
Week 14	4	2
Week 30	1	NA
Week 54	NA	NA
At discontinuation	NA	2

12. Secondary Outcome

Title	Interleukin-6 (IL-6) Concentration in CSF for Neuro-BD
Time Frame	Week 0, Week 14, Week 30, Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Acute Neuro BD (Patient No.1)	Acute Neuro-BD (Patient No.2)	Chronic Progressive Neuro-BD
Arm/Group Description
Measure Participants	1	1	1
Week 0	145	2.5	64.5
Week 14	2.2	23	35.1
Week 30	1.4	NA	5.4
Week 54	1.5	NA	32.1
At discontinuation	NA	6.5	NA

13. Secondary Outcome

Title	The Number of Improved Intestinal BD Patients From Baseline
Description	The investigator assessed clinical symptoms associated with intestinal BD in one week before the day of evaluation as " No symptom, Very slightly poor, Slightly poor, Poor or Extremely poor". We calculated improved patients in comparison with those for Week 0.
Time Frame	Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intestinal BD
Arm/Group Description	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.
Measure Participants	11
Week 2 (n=11)	7 63.6%
Week 6 (n=11)	9 81.8%
Week 10 (n=11)	9 81.8%
Week 14 (n=11)	8 72.7%
Week 18 (n=11)	11 100%
Week 22 (n=11)	10 90.9%
Week 26 (n=11)	10 90.9%
Week 30 (n=11)	10 90.9%
Week 34 (n=11)	10 90.9%
Week 38 (n=11)	9 81.8%
Week 42 (n=10)	8 72.7%
Week 46 (n=10)	8 72.7%
Week 50 (n=10)	8 72.7%
Week 54 (n=10)	8 72.7%
Final (n=11)	9 81.8%

14. Secondary Outcome

Title	Change From Baseline in Clinical Symptoms Associated With Neuro-BD Patients
Description	The investigator assessed the clinical symptoms associated with neuro-BD at each time point of the evaluation in compared to Week 0, in accordance with the categories as "No symptom, Improved, Unchanged or Worsened".
Time Frame	Week 2, 6, 10, then every 4 weeks after Week 14 to Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Acute Neuro BD (Patient No.1)	Acute Neuro-BD (Patient No.2)	Chronic Progressive Neuro-BD
Arm/Group Description
Measure Participants	1	1	1
No symptom, Week 2	1 9.1%	1 50%	0 0%
Improved, Week 2	0 0%	0 0%	0 0%
Unchanged, Week 2	0 0%	0 0%	1 100%
Worsened, Week 2	0 0%	0 0%	0 0%
No symptom, Week 6	1 9.1%	1 50%	1 100%
Improved, Week 6	0 0%	0 0%	0 0%
Unchanged, Week 6	0 0%	0 0%	0 0%
Worsened, Week 6	0 0%	0 0%	0 0%
No symptom, Week 10	1 9.1%	0 0%	0 0%
Improved, Week 10	0 0%	1 50%	1 100%
Unchanged, Week 10	0 0%	0 0%	0 0%
Worsened, Week 10	0 0%	0 0%	0 0%
No symptom, Week 14	1 9.1%	0 0%	1 100%
Improved, Week 14	0 0%	1 50%	0 0%
Unchanged, Week 14	0 0%	0 0%	0 0%
Worsened, Week 14	0 0%	0 0%	0 0%
No symptom, Week 18	1 9.1%	0 0%	1 100%
Improved, Week 18	0 0%	1 50%	0 0%
Unchanged, Week 18	0 0%	0 0%	0 0%
Worsened, Week 18	0 0%	0 0%	0 0%
No symptom, Week 22	0 0%	0 0%	1 100%
Improved, Week 22	1 9.1%	0 0%	0 0%
Unchanged, Week 22	0 0%	1 50%	0 0%
Worsened, Week 22	0 0%	0 0%	0 0%
No symptom, Week 26	1 9.1%	NA NaN	1 100%
Improved, Week 26	0 0%	NA NaN	0 0%
Unchanged, Week 26	0 0%	NA NaN	0 0%
Worsened, Week 26	0 0%	NA NaN	0 0%
No symptom, Week 30	1 9.1%	NA NaN	1 100%
Improved, Week 30	0 0%	NA NaN	0 0%
Unchanged, Week 30	0 0%	NA NaN	0 0%
Worsened, Week 30	0 0%	NA NaN	0 0%
No symptom, Week 34	1 9.1%	NA NaN	1 100%
Improved, Week 34	0 0%	NA NaN	0 0%
Unchanged, Week 34	0 0%	NA NaN	0 0%
Worsened, Week 34	0 0%	NA NaN	0 0%
No symptom, Week 38	1 9.1%	NA NaN	1 100%
Improved, Week 38	0 0%	NA NaN	0 0%
Unchanged, Week 38	0 0%	NA NaN	0 0%
Worsened, Week 38	0 0%	NA NaN	0 0%
No symptom, Week 42	1 9.1%	NA NaN	1 100%
Improved, Week 42	0 0%	NA NaN	0 0%
Unchanged, Week 42	0 0%	NA NaN	0 0%
Worsened, Week 42	0 0%	NA NaN	0 0%
No symptom, Week 46	1 9.1%	NA NaN	1 100%
Improved, Week 46	0 0%	NA NaN	0 0%
Unchanged, Week 46	0 0%	NA NaN	0 0%
Worsened, Week 46	0 0%	NA NaN	0 0%
No symptom, Week 50	1 9.1%	NA NaN	1 100%
Improved, Week 50	0 0%	NA NaN	0 0%
Unchanged, Week 50	0 0%	NA NaN	0 0%
Worsened, Week 50	0 0%	NA NaN	0 0%
No symptom, Week 54	1 9.1%	NA NaN	1 100%
Improved, Week 54	0 0%	NA NaN	0 0%
Unchanged, Week 54	0 0%	NA NaN	0 0%
Worsened, Week 54	0 0%	NA NaN	0 0%
No symptom, at discontinuations	NA NaN	1 50%	NA NaN
Improved, at discontinuations	NA NaN	0 0%	NA NaN
Unchanged, at discontinuations	NA NaN	0 0%	NA NaN
Worsened, at discontinuations	NA NaN	0 0%	NA NaN

15. Secondary Outcome

Title	Change From Baseline in Clinical Symptoms Associated With Vascular BD Patients
Description	The investigator assessed the clinical symptoms associated with vascular-BD at each time point of the evaluation in compared to Week 0, in accordance with the categories as "No symptom, Improved, Unchanged or Worsened".
Time Frame	Week 2, 6, 10, then every 4 weeks after Week 14 to Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vascular-BD
Arm/Group Description	A-650, 5 mg/kg, iv infusion over a period of more than 2 hours. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.
Measure Participants	4
No symptom, Week 2	1 9.1%
Improved, Week 2	2 18.2%
Unchanged, Week 2	1 9.1%
Worsened, Week 2	0 0%
No symptom, Week 6	1 9.1%
Improved, Week 6	2 18.2%
Unchanged, Week 6	1 9.1%
Worsened, Week 6	0 0%
No symptom, Week 10	1 9.1%
Improved, Week 10	2 18.2%
Unchanged, Week 10	1 9.1%
Worsened, Week 10	0 0%
No symptom, Week 14	1 9.1%
Improved, Week 14	2 18.2%
Unchanged, Week 14	1 9.1%
Worsened, Week 14	0 0%
No symptom, Week 18	0 0%
Improved, Week 18	4 36.4%
Unchanged, Week 18	0 0%
Worsened, Week 18	0 0%
No symptom, Week 22	0 0%
Improved, Week 22	3 27.3%
Unchanged, Week 22	1 9.1%
Worsened, Week 22	0 0%
No symptom, Week 26	0 0%
Improved, Week 26	3 27.3%
Unchanged, Week 26	1 9.1%
Worsened, Week 26	0 0%
No symptom, Week 30	0 0%
Improved, Week 30	4 36.4%
Unchanged, Week 30	0 0%
Worsened, Week 30	0 0%
No symptom, Week 34	0 0%
Improved, Week 34	3 27.3%
Unchanged, Week 34	1 9.1%
Worsened, Week 34	0 0%
No symptom, Week 38	0 0%
Improved, Week 38	4 36.4%
Unchanged, Week 38	0 0%
Worsened, Week 38	0 0%
No symptom, Week 42	0 0%
Improved, Week 42	4 36.4%
Unchanged, Week 42	0 0%
Worsened, Week 42	0 0%
No symptom, Week 46	0 0%
Improved, Week 46	4 36.4%
Unchanged, Week 46	0 0%
Worsened, Week 46	0 0%
No symptom, Week 50	0 0%
Improved, Week 50	4 36.4%
Unchanged, Week 50	0 0%
Worsened, Week 50	0 0%
No symptom, Week 54	0 0%
Improved, Week 54	4 36.4%
Unchanged, Week 54	0 0%
Worsened, Week 54	0 0%
No symptom, Final	0 0%
Improved, Final	4 36.4%
Unchanged, Final	0 0%
Worsened, Final	0 0%

Adverse Events

Arm/Group Title	TA-650
Arm/Group Description	TA-650: TA-650 will be intravenously infused at a dosage of 5 mg/kg slowly over a period of more than 2 hours at the first administration (weeks 0), 2, and 6, and then every 8 weeks up to week 46. If the criteria for a dosage escalation are met at the evaluation after week 30, TA-650 will be administered at a dosage of 10 mg/kg after week 30.
All Cause Mortality
	TA-650
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	TA-650
	Affected / at Risk (%)	# Events
Total	2/18 (11.1%)
Eye disorders
Cataract	1/18 (5.6%)
Vascular disorders
Behcet's syndrome	1/18 (5.6%)
Other (Not Including Serious) Adverse Events
	TA-650
	Affected / at Risk (%)	# Events
Total	17/18 (94.4%)
Cardiac disorders
Palpitations	1/18 (5.6%)
Eye disorders
Conjunctival haemorrhage	1/18 (5.6%)
Dry eye	1/18 (5.6%)
Gastrointestinal disorders
Constipation	1/18 (5.6%)
Gastritis	1/18 (5.6%)
Nausea	1/18 (5.6%)
Proctalgia	2/18 (11.1%)
General disorders
Malaise	1/18 (5.6%)
Puncture site reaction	1/18 (5.6%)
Pyrexia	2/18 (11.1%)
Hepatobiliary disorders
Cholelithiasis	1/18 (5.6%)
Liver disorder	1/18 (5.6%)
Infections and infestations
Bronchitis	1/18 (5.6%)
Enteritis infectious	2/18 (11.1%)
Gastroenteritis	2/18 (11.1%)
Gastroenteritis norovirus	1/18 (5.6%)
Influenza	1/18 (5.6%)
Nasopharyngitis	4/18 (22.2%)
Periodontitis	1/18 (5.6%)
Pharyngitis	1/18 (5.6%)
Pulpitis dental	1/18 (5.6%)
Tinea pedis	1/18 (5.6%)
Tonsillitis	1/18 (5.6%)
Upper respiratory tract infection	5/18 (27.8%)
Injury, poisoning and procedural complications
Administration related reaction	1/18 (5.6%)
Arthropod sting	1/18 (5.6%)
Contusion	1/18 (5.6%)
Excoriation	1/18 (5.6%)
Ligament sprain	2/18 (11.1%)
Limb injury	1/18 (5.6%)
Post lumbar puncture syndrome	1/18 (5.6%)
Tongue injury	1/18 (5.6%)
Wound	1/18 (5.6%)
Investigations
Antinuclear antibody increased	2/18 (11.1%)
Double stranded DNA antibody positive	8/18 (44.4%)
White blood cell count decreased	1/18 (5.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/18 (11.1%)
Back pain	2/18 (11.1%)
Muscle rigidity	1/18 (5.6%)
Myalgia	1/18 (5.6%)
Tenosynovitis	1/18 (5.6%)
Nervous system disorders
Dizziness	1/18 (5.6%)
Dysaesthesia	1/18 (5.6%)
Headache	2/18 (11.1%)
Hypoaesthesia	1/18 (5.6%)
Intracranial hypotension	1/18 (5.6%)
Somnolence	1/18 (5.6%)
Tension headache	1/18 (5.6%)
Psychiatric disorders
Depressive symptom	1/18 (5.6%)
Somatoform disorder	1/18 (5.6%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/18 (5.6%)
Epistaxis	1/18 (5.6%)
Upper respiratory tract inflammation	1/18 (5.6%)
Skin and subcutaneous tissue disorders
Acne	2/18 (11.1%)
Asteatosis	1/18 (5.6%)
Dermatitis acneiform	1/18 (5.6%)
Dermatitis contact	1/18 (5.6%)
Drug eruption	1/18 (5.6%)
Dyshidrotic eczema	1/18 (5.6%)
Rash	1/18 (5.6%)
Urticaria	1/18 (5.6%)
Vascular disorders
Behcet's syndrome	1/18 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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