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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Behcet's Disease, Behcet Syndrome, Neuro-Behcet's Disease

Intervention / Treatment
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* Drug: TA-650


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TA-650<br> | Drug: TA-650<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Response at 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. | Week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Response at Week 14 and 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. | Week 14, Week 54 | 
| Patient General Visual Analogue Scale (VAS) for the Clinical Symptoms Associated With Each BD | 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. | Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54 | 
| Imaging Findings:Endoscopic Examination for Intestinal BD | 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. | Week 14, Week 30, Week 54 | 
| Imaging Findings: Brain Magnetic Resonance Imaging (MRI) for Acute Neuro-BD | 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. | Week 14, Week 30, Week 54 | 
| Imaging Findings: Brainstem MRI for Chronic Neuro-BD | 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. | Week 14, Week 30, Week 54 | 
| Imaging Findings: CT, PET/CT for Vascular-BD | 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. | Week 14, Week 30, Week 54 | 
| Concentration of Inflammatory Biomarker (C-reactive Protein (CRP)) of Intestinal BD | 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. | Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54 | 
| Concentration of Inflammatory Biomarker (CRP) of Vascular BD | 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. | Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54 | 
| Level of Inflammatory Biomarker (Erythrocyte Sedimentation Rate) of Vascular BD | 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. | Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54 | 
| Cell Counts in Cerebrospinal Fluid (CSF) for Acute Neuro-BD | 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. | Week 0, Week 14, Week 30, Week 54 | 
| Interleukin-6 (IL-6) Concentration in CSF for Neuro-BD |  | Week 0, Week 14, Week 30, Week 54 | 
| The Number of Improved Intestinal BD Patients From Baseline | 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. | Week 0, 2, 6, 10, then every 4 weeks after Week 14 to Week 54 | 
| Change From Baseline in Clinical Symptoms Associated With Neuro-BD Patients | 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. | Week 2, 6, 10, then every 4 weeks after Week 14 to Week 54 | 
| Change From Baseline in Clinical Symptoms Associated With Vascular BD Patients | 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. | Week 2, 6, 10, then every 4 weeks after Week 14 to Week 54 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Behcet's disease, intestinal Behcet's disease, neuro-Behcet's disease, vascular Behcet's disease