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

Phase 3

Completed

Conditions: Intestinal Behçet's Disease

Interventions: Biological: Adalimumab

Registration Number: NCT01243671

Lead Sponsor: AbbVie (prior sponsor, Abbott)

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Adalimumab	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Marked Improvement at Week 24	24 weeks	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).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Marked Improvement at Week 52	52 weeks	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).
Number of Participants With Complete Remission at Week 24 and Week 52	24 weeks, 52 weeks	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.
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	24 weeks, 52 weeks	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.
Number of Participants With Endoscopic Improvement Grades 0, ≤1 and ≤2 at Week 24 and Week 52	24 weeks, 52 weeks	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).
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	24 weeks, 52 weeks	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.
Number of Participants With Resolution of Behçet's Disease Symptoms (Other Than Gastrointestinal Symptoms) at Week 24 and Week 52	24 weeks, 52 weeks	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).
Mean Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 24 and Week 52	Baseline, 24 weeks, 52 weeks	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).
Mean Change From Baseline in Short Form-36 (SF-36) Summary Scores at Week 24 and Week 52	Baseline, 24 weeks, 52 weeks	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).
Median Change From Baseline in C-Reactive Protein (CRP) at Week 24 and Week 52	Baseline, 24 weeks, 52 weeks	C-Reactive Protein (CRP) normal range was defined as ≤0.3 mg/dL.

Trial Locations

Locations (12): Site Reference ID/Investigator# 46725
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Nishinomiya-shi, Japan
Site Reference ID/Investigator# 46728
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Nagoya-shi, Japan
Site Reference ID/Investigator# 46738
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Chikushino, Japan
Site Reference ID/Investigator# 46723
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Kurume, Japan
Site Reference ID/Investigator# 46722
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Sagamihara-shi, Japan
Site Reference ID/Investigator# 46737
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Tokyo, Japan
Site Reference ID/Investigator# 46724
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Takatsuki-shi, Japan
Site Reference ID/Investigator# 46729
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Tokyo, Japan
Site Reference ID/Investigator# 59578
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Sapporo-shi, Japan
Site Reference ID/Investigator# 46730
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Osaka-shi, Japan
Site Reference ID/Investigator# 46726
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Sakura, Japan
Site Reference ID/Investigator# 46733
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Yokohama-shi, Japan