A Study of Adalimumab in Japanese Subjects With Active Ankylosing Spondylitis

Study Overview
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Brief Summary
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To evaluate efficacy, safety and pharmacokinetics of adalimumab in Japanese subjects with active ankylosing spondylitis

Detailed Description
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It is reported that the prevalence of Ankylosing Spondylitis (AS) in Japanese patients is extremely lower than that of Caucasians; therefore, a controlled, double-blind study with similar sample size in Western studies for active AS in Japan was not able to be conducted. As a result, this study was conducted with an open-label design to investigate efficacy, safety and pharmacokinetics of adalimumab in Japanese subjects with active AS. The inclusion criteria and primary endpoint measurement (Achieving Assessment in Ankylosing Spondylitis 20 at Week 12) were designed the same as the Western studies for active AS in consideration with the confirmation of Western data. Treatment with adalimumab was to be continued until the approval of adalimumab for AS in Japanese subjects with active AS.

Official Title
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A Multi-Center, Open-Label Efficacy, Safety, and Pharmacokinetic Study of Adalimumab in Japanese Subjects With Active Ankylosing Spondylitis

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Biological: adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject who meets the definition of Ankylosing Spondylitis based on the Modified New York Criteria, has a diagnosis of active Ankylosing Spondylitis and has had an inadequate response to or intolerance to one or more nonsteroidal anti-inflammatory drugs Exclusion Criteria: History of cancer, lymphoma, leukemia or lymphoproliferative disease, active TB, HIV Previously received anti-TNF therapy Spinal surgery or joint surgery involving joints to be assessed within 2 months prior to the Screening

Ages Eligible for Study
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Minimum Age: 15 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: Adalimumab<br>Adalimumab 40 mg or 80 mg subcutaneously (SC) administered every other week (eow) until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan. All subjects received 40 mg of adalimumab SC eow at Baseline. The subjects who completed 16 weeks of therapy and who failed to achieve Assessments in Ankylosing Spondylitis 20 (ASAS 20) response on or after Week 16, could increase the dose of adalimumab to 80 mg eow. When the dose was increased, the higher dose was to be continued during the rest of the study. | Biological: adalimumab<br>* 40 mg or 80 mg every other week, subcutaneous<br>* Other names: Humira;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Achieving Assessment in Ankylosing Spondylitis 20 (ASAS 20) at Week 12 | ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 20 = at least 20% improvement (vs. baseline) and an absolute improvement ≥ 10 units on a 0 - 100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening (defined as a worsening of ≥ 20% and a net worsening of ≥ 10 units) in the remaining domain. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Achieving ASAS 20 | ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 20 = 20% improvement (vs. baseline) and an absolute improvement ≥ 10 units on a 0-100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening (defined as a worsening of ≥ 20% and a net worsening of ≥ 10 units) in the remaining domain. | Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Number of Subjects Achieving ASAS 50 | ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 50 = at least 50% improvement (vs. baseline) and an absolute improvement ≥ 20 units on a 0-100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening (defined as a worsening of ≥ 20% and a net worsening of ≥ 10 units) in the remaining domain. | Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Number of Subjects Achieving ASAS 70 | ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 70 = at least 70% improvement (vs. baseline) and an absolute improvement ≥ 30 units on a 0-100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening (defined as a worsening of ≥ 20% and a net worsening of ≥ 10 units) in the remaining domain. | Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Number of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50) | BASDAI is a validated self assessment tool used to determine disease activity in subjects with Ankylosing Spondylitis (AS). Utilizing a Visual Analog Scale (VAS) of 0-10 (0=none and 10=very severe) subjects answered 6 questions measuring discomfort, pain, fatigue, and morning stiffness. BASDAI 50 = at least 50% improvement (vs. baseline) in BASDAI. | Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Mean Change From Baseline in Patient's Global Assessment of Disease Activity | Subject's assessment of disease activity using a Visual Analog Scale (VAS) of 0 - 100 mm (0 = none and 100 = severe). | Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Mean Change From Baseline in Total Back Pain | Subject assessed his/her back pain by using a Visual Analog Scale (VAS) of 0 - 100 mm (0 = no pain and 100 = most severe pain). | Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) | BASFI is a validated self assessment tool that determines the degree of functional limitation in AS subjects. Utilizing a VAS of 0-100 mm (0=easy, 100=impossible), subjects answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions. | Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Mean Change From Baseline in C-Reactive Protein (CRP) | CRP is a marker of inflammation and measured in mg/dL. A higher level is consistent with inflammation. | Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Number of Subjects Achieving Assessment in Ankylosing Spondylitis (ASAS) 5/6. | ASAS 5/6 consists of 6 domains: the 4 used in ASAS 20 (patient global assessment of disease activity, pain, function, inflammation) plus spinal mobility and an acute phase reactant, C Reactive Protein (CRP). Achieving ASAS 5/6 requires a 20% improvement compared to baseline in ≥ 5 domains (each domain measured on a 0 - 100 scale [0 = no disease activity; 100 = high disease activity]). | Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Number of Subjects Achieving Assessment in Ankylosing Spondylitis 40 (ASAS 40) | ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS = 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 40 = at least 40% improvement (vs. baseline) and an absolute improvement ≥ 20 units on a 0-100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening in remaining domain. | Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Number of Subjects Achieving Assessment in Ankylosing Spondylitis Partial Remission | Partial remission is defined as a score of less than 20 units (on a scale of 0-100; 0=no disease activity and 100=high disease activity) in each of the 4 Assessments in Ankylosing Spondylitis (ASAS) domains: patient global assessment of disease activity, pain, function, and inflammation. | Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Mean Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) | BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: tragus to wall distance, lumbar flexion, cervical rotation, lumbar side flexion, and intermalleolar distance. Each measure was scored 0-2 (0=normal mobility/mild disease involvement, 1=moderate disease involvement, 2=severe disease involvement) to give a final total score ranging from 0 to 10. The higher the BASMI score, the more severe was the subject's limitation of movement due to their AS. | Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Mean Change From Baseline in Chest Expansion | Chest expansion is the difference in centimeters between full expiration and full inspiration, measured at the 4th inter-costal space. An increase in chest expansion represents improvement. | Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Mean Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) | Assessment of enthesitis was performed in the following 7 domains: 1) 1st costochondral joint left and right, 2) 7th costochondral joint left and right, 3) posterior superior iliac spine left and right, 4) anterior superior iliac spine left and right, 5) iliac crest left and right, 6) 5th lumbar spinous process and 7) proximal insertion of Achilles tendon left and right. Each domain was graded for the presence (1) and absence (0) of tenderness yielding total MASES ranging from 0 (no tenderness) to 13 (worst possible score; severe tenderness). | Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Mean Change From Baseline in Nocturnal Pain | Nocturnal pain assessed by subjects using a Visual Analog Scale (VAS) of 0 - 100 mm (0 = no pain and 100 = worst possible pain). | Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Mean Change From Baseline in Swollen Joint Count for 44 Joints (SJC 44) | The number of swollen joints among 22 anatomical joints for both the right and left side of the body were assessed by a joint evaluator where the presence of a swollen joint was scored as 1 and absence as 0. The total SJC was derived by the sum of the scores for a range of SJC from 0 (best possible score; no swollen joints) to 44 (worse possible score; all joints swollen). | Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Mean Change From Baseline in Tender Joint Count for 46 Joints (TJC 46) | The number of tender or painful joints among 23 anatomical joints for both the right and left side of the body were assessed by a joint evaluator where the presence of a tender or painful joint was scored as 1 and absence as 0. The total TJC was derived by the sum of the scores for a range of TJC from 0 (best possible score; no tender or painful joints) to 46 (worst possible score; all joints tender or painful). | Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 
| Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These are summarized in a physical component summary (PCS) and mental component summary (MCS) score. The score for a section is an average of the individual question scores, which are scaled 0-100 (0=lowest level of functioning; 100=highest level of functioning). | Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ankylosing Spondylitis