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

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

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.

Study Overview

• Status: Completed
• Conditions: Behcet Syndrome; Behcet's Disease; Neuro-Behcet's Disease
• Intervention / Treatment: Drug: TA-650

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chubu, Japan
    • Investigational site
  • Hokkaido, Japan
    • Investigational site
  • Kanto, Japan
    • Investigational site
  • Kinki, Japan
    • Investigational site
  • Kyusyu, Japan
    • Investigational site
  • Tohoku, Japan
    • Investigational site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma Corporation
• Investigators: Study Director: Yoshiaki Ishigatsubo, MD, Ph.D, Yokohama City University Graduate School of Medicine; Study Director: Shunsei Hirohata, MD, Kitasato University School of Medicine

Publications and helpful links

General Publications

• Hibi T, Hirohata S, Kikuchi H, Tateishi U, Sato N, Ozaki K, Kondo K, Ishigatsubo Y. Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease: Efficacy, safety, and pharmacokinetics in a multicenter, prospective, open-label, single-arm phase 3 study. Medicine (Baltimore). 2016 Jun;95(24):e3863. doi: 10.1097/MD.0000000000003863. Erratum In: Medicine (Baltimore). 2016 Aug 07;95(31):e5074.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: February 6, 2012
• First Submitted That Met QC Criteria: February 13, 2012
• First Posted (Estimate): February 14, 2012

Study Record Updates

• Last Update Posted (Estimate): December 16, 2016
• Last Update Submitted That Met QC Criteria: October 25, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Behcet's disease; intestinal Behcet's disease; neuro-Behcet's disease; vascular Behcet's disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Eye Diseases; Genetic Diseases, Inborn; Stomatognathic Diseases; Mouth Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Vasculitis; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Skin Diseases, Vascular; Behcet Syndrome
• Other Study ID Numbers: TA-650-23