A Study of Adalimumab in Japanese Subjects With Intestinal Behçet's Disease

A Multi-Center Study of Adalimumab in Japanese Subjects With Intestinal Behçet's Disease

To investigate efficacy, safety and pharmacokinetics of adalimumab subcutaneous (sc) for Japanese subjects with intestinal Behçet's disease who are refractory to conventional therapies.

Study Overview

• Status: Completed
• Conditions: Intestinal Behçet's Disease
• Intervention / Treatment: Biological: Adalimumab

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chikushino, Japan
    • Site Reference ID/Investigator# 46738
  • Kurume, Japan
    • Site Reference ID/Investigator# 46723
  • Nagoya-shi, Japan
    • Site Reference ID/Investigator# 46728
  • Nishinomiya-shi, Japan
    • Site Reference ID/Investigator# 46725
  • Osaka-shi, Japan
    • Site Reference ID/Investigator# 46730
  • Sagamihara-shi, Japan
    • Site Reference ID/Investigator# 46722
  • Sakura, Japan
    • Site Reference ID/Investigator# 46726
  • Sapporo-shi, Japan
    • Site Reference ID/Investigator# 59578
  • Takatsuki-shi, Japan
    • Site Reference ID/Investigator# 46724
  • Tokyo, Japan
    • Site Reference ID/Investigator# 46729
  • Tokyo, Japan
    • Site Reference ID/Investigator# 46737
  • Yokohama-shi, Japan
    • Site Reference ID/Investigator# 46733

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Intestinal Behçet's disease
• Patients with typical ulcer at ileocecal region
• Patients who have failed conventional treatment

Exclusion Criteria:

• Crohn's disease
• History of ileocecal resection
• History of tuberculosis (TB)
• Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adalimumab; Adalimumab 160 mg at Week 0, 80 mg at Week 2 and 40 mg every other week (eow) starting at Week 4 to Week 50, subcutaneous injection. After Week 52, participants could continue the treatment with 40 mg eow until the day before approval of adalimumab for intestinal Behçet's disease in Japan.	Biological: Adalimumab; Other Names: ABT-D2E7, Humira

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Marked Improvement at Week 24	Marked improvement is defined as the combination of both global assessment of gastrointestinal (GI) symptoms and endoscopic improvement grades of ≤1. Global assessment of GI symptoms is a participant-assessed, investigator-confirmed grading of global symptoms from 0 to 4: 0=free of symptoms; 1=symptoms existed in past 2 weeks but did not affect participant's daily life; 2=symptoms existed in past 2 weeks and slightly affected participant's daily life; 3=symptoms existed in past 2 weeks and affected participant's daily life; 4=symptoms existed in past 2 weeks and critically affected participant's daily life. Endoscopic improvement was assessed in 4 grades compared to the screening endoscopy based on the longest diameter (none, ≥1 cm to <2 cm, ≥2 cm to <3 cm, ≥3 cm) of ileocecal largest open ulcer (area of mucosal defect). Grades are: 0=healing; 1=marked reduction (reduction to ≤1/4); 2=reduction (reduction to ≤1/2 - 1/4); 3=no change or worse (reduction less than 1/2 or expansion).	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Marked Improvement at Week 52	Marked improvement is defined as the combination of both global assessment of gastrointestinal (GI) symptoms and endoscopic improvement grades of ≤1. Global assessment of GI symptoms is a participant-assessed, investigator-confirmed grading of global symptoms from 0 to 4: 0=free of symptoms; 1=symptoms existed in past 2 weeks but did not affect participant's daily life; 2=symptoms existed in past 2 weeks and slightly affected participant's daily life; 3=symptoms existed in past 2 weeks and affected participant's daily life; 4=symptoms existed in past 2 weeks and critically affected participant's daily life. Endoscopic improvement was assessed in 4 grades compared to the screening endoscopy based on the longest diameter (none, ≥1 cm to <2 cm, ≥2 cm to <3 cm, ≥3 cm) of ileocecal largest open ulcer (area of mucosal defect). Grades are: 0=healing; 1=marked reduction (reduction to ≤1/4); 2=reduction (reduction to ≤1/2 - 1/4); 3=no change or worse (reduction less than 1/2 or expansion).	52 weeks
Number of Participants With Complete Remission at Week 24 and Week 52	Complete remission was defined as both endoscopic improvement and global assessment of gastrointestinal symptoms grades of 0. Endoscopic improvement was assessed in 4 grades compared to the screening (baseline) endoscopy based on the longest diameter (none, ≥1 cm to <2 cm, ≥2 cm to <3 cm, ≥3 cm) of ileocecal largest open ulcer (area of mucosal defect). Grades are: 0=healing; 1=marked reduction (reduction to ≤1/4); 2=reduction (reduction to ≤1/2 - 1/4); 3=no change or worse (reduction less than 1/2 or expansion). Global assessment of gastrointestinal symptoms is a participant-assessed, investigator-confirmed grading of global symptoms from 0 to 4: 0=free of symptoms; 1=symptoms existed in past 2 weeks but did not affect participant's daily life; 2=symptoms existed in past 2 weeks and slightly affected participant's daily life; 3=symptoms existed in past 2 weeks and affected participant's daily life; 4=symptoms existed in past 2 weeks and critically affected participant's daily life.	24 weeks, 52 weeks
Number of Participants With a Global Assessment of Gastrointestinal Symptoms Grade 0 or ≤1 and Improvement of ≥1 Grade at Week 24 and Week 52	Study participants completed a global assessment of their gastrointestinal symptoms (Behçet's disease symptoms other than gastrointestinal symptoms were excluded) during 2 weeks before assessment visit on a 5-grade scale. The investigator confirmed this assessment via interview with participants. Assessment is graded from 0 to 4: 0=free of symptoms; 1=symptoms existed in past 2 weeks but did not affect participant's daily life; 2=symptoms existed in past 2 weeks and slightly affected participant's daily life; 3=symptoms existed in past 2 weeks and affected participant's daily life; 4=symptoms existed in past 2 weeks and critically affected participant's daily life. Global assessment of grade 0 or ≤1 and improvement of ≥1 (from baseline) is presented.	24 weeks, 52 weeks
Number of Participants With Endoscopic Improvement Grades 0, ≤1 and ≤2 at Week 24 and Week 52	Endoscopic improvement was assessed in 4 grades compared to the screening (baseline) endoscopy based on the longest diameter (none, ≥1 cm to <2 cm, ≥2 cm to <3 cm, ≥3 cm) of ileocecal largest open ulcer (area of mucosal defect). Grades are: 0=healing; 1=marked reduction (reduction to ≤1/4); 2=reduction (reduction to ≤1/2 - 1/4); 3=no change or worse (reduction less than 1/2 or expansion).	24 weeks, 52 weeks
Number of Participants With Abdominal Pain, Diarrhea and Other Gastrointestinal (GI) Symptoms Grade ≤1 and Improvement of ≥1 Grade at Week 24 and Week 52	Participants assessed their abdominal pain, diarrhea and other gastrointestinal symptoms (abdominal discomfort, abdominal fullness, etc) during 2 weeks before assessment visit in 5 grades. Investigator confirmed the assessment through interview with participants. Assessment is graded from 0 to 4: 0=free of symptoms; 1=symptoms existed in past 2 weeks but did not affect participant's daily life; 2=symptoms existed in past 2 weeks and slightly affected participant's daily life; 3=symptoms existed in past 2 weeks and affected participant's daily life; 4=symptoms existed in past 2 weeks and critically affected participant's daily life. Improvement of ≥1 grade from baseline is also presented.	24 weeks, 52 weeks
Number of Participants With Resolution of Behçet's Disease Symptoms (Other Than Gastrointestinal Symptoms) at Week 24 and Week 52	Investigators assessed oral aphthous (mouth ulcers), skin symptoms, eye symptoms and vulval (genital) ulcers during 4 weeks before study visit via participant interview, using the following grades. Oral aphthous: 0=None; 1=Symptom existed less than 2 weeks in recent 4 weeks; 2=Symptom existed 2 weeks or more in recent 4 weeks; 3=Symptom existed mostly in recent 4 weeks. Skin (Erythema nodosum rash): 0=None; 1=Symptom existed less than 2 weeks in recent 4 weeks; 2=Symptom existed 2 weeks or more in recent 4 weeks; 3=Symptom existed mostly in recent 4 weeks. Eye (Uveitis): 0=None; 1=one eye crisis in recent 4 weeks; 2=two eye crises in recent 4 weeks; 3=three eye crises in recent 4 weeks. Vulval (genital) ulcer: 0=None; 1=Symptom existed less than 2 weeks in recent 4 weeks; 2=Symptom existed 2 weeks or more in recent 4 weeks; 3=Symptom existed mostly in recent 4 weeks. Resolution was defined as: Behçet's disease symptoms other than gastrointestinal symptoms were graded 0 (disappeared).	24 weeks, 52 weeks
Mean Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 24 and Week 52	Inflammatory Bowel Disease Questionnaire (IBDQ) is the standard questionnaire to assess the quality of life of patients with inflammatory bowel disease. The IBDQ is a 32-item questionnaire consisting of 4 dimensions: bowel-related symptoms, systemic function, social function and emotional status. The responses to each question within each domain range from 1 (significant impairment) to 7 (no impairment), with total score ranging from 32 (very poor) to 224 (perfect health-related quality of life).	Baseline, 24 weeks, 52 weeks
Mean Change From Baseline in Short Form-36 (SF-36) Summary Scores at Week 24 and Week 52	The Short-Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 score indicates alleviation of the disease and a decrease in score indicates aggravation of disease. The physical component reflects activity level, activity limitations, pain and rating of one's health. Score on the physical component ranges from 0 (poorest health) to 100 (best health). The mental component reflects vitality, social functioning, role-emotional and mental health. Score on the mental component ranges from 0 (poorest health) to 100 (best health).	Baseline, 24 weeks, 52 weeks
Median Change From Baseline in C-Reactive Protein (CRP) at Week 24 and Week 52	C-Reactive Protein (CRP) normal range was defined as ≤0.3 mg/dL.	Baseline, 24 weeks, 52 weeks

Collaborators and Investigators

• Sponsor: AbbVie (prior sponsor, Abbott)
• Collaborators: Eisai Co., Ltd.
• Investigators: Study Director: Morio Ozawa, MS, AbbVie GK.

Publications and helpful links

General Publications

• Inoue N, Kobayashi K, Naganuma M, Hirai F, Ozawa M, Arikan D, Huang B, Robinson AM, Thakkar RB, Hibi T. Long-term safety and efficacy of adalimumab for intestinal Behcet's disease in the open label study following a phase 3 clinical trial. Intest Res. 2017 Jul;15(3):395-401. doi: 10.5217/ir.2017.15.3.395. Epub 2017 Jun 12.
• Tanida S, Inoue N, Kobayashi K, Naganuma M, Hirai F, Iizuka B, Watanabe K, Mitsuyama K, Inoue T, Ishigatsubo Y, Suzuki Y, Nagahori M, Motoya S, Nakamura S, Arora V, Robinson AM, Thakkar RB, Hibi T. Adalimumab for the treatment of Japanese patients with intestinal Behcet's disease. Clin Gastroenterol Hepatol. 2015 May;13(5):940-8.e3. doi: 10.1016/j.cgh.2014.08.042. Epub 2014 Sep 19.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: November 17, 2010
• First Submitted That Met QC Criteria: November 17, 2010
• First Posted (Estimate): November 18, 2010

Study Record Updates

• Last Update Posted (Estimate): July 25, 2014
• Last Update Submitted That Met QC Criteria: June 27, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Behçet's, intestinal
• 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; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: M11-509

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No