Trial record 1 of 230 for:    Ankylosing Spondylitis
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A Study of Adalimumab in Japanese Subjects With Active Ankylosing Spondylitis

This study has been completed.
Sponsor:
Collaborator:
Eisai Co., Ltd.
Information provided by (Responsible Party):
Abbott
ClinicalTrials.gov Identifier:
NCT00667355
First received: April 24, 2008
Last updated: January 24, 2012
Last verified: January 2012
  Purpose

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


Condition Intervention Phase
Ankylosing Spondylitis
Biological: adalimumab
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Center, Open-Label Efficacy, Safety, and Pharmacokinetic Study of Adalimumab in Japanese Subjects With Active Ankylosing Spondylitis

Resource links provided by NLM:


Further study details as provided by Abbott:

Primary Outcome Measures:
  • Number of Subjects Achieving Assessment in Ankylosing Spondylitis 20 (ASAS 20) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Subjects Achieving ASAS 20 [ Time Frame: Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Achieving ASAS 50 [ Time Frame: Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Achieving ASAS 70 [ Time Frame: Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50) [ Time Frame: Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in Patient's Global Assessment of Disease Activity [ Time Frame: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    Subject's assessment of disease activity using a Visual Analog Scale (VAS) of 0 - 100 mm (0 = none and 100 = severe).

  • Mean Change From Baseline in Total Back Pain [ Time Frame: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) [ Time Frame: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in C-Reactive Protein (CRP) [ Time Frame: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    CRP is a marker of inflammation and measured in mg/dL. A higher level is consistent with inflammation.

  • Number of Subjects Achieving Assessment in Ankylosing Spondylitis (ASAS) 5/6. [ Time Frame: Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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]).

  • Number of Subjects Achieving Assessment in Ankylosing Spondylitis 40 (ASAS 40) [ Time Frame: Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Achieving Assessment in Ankylosing Spondylitis Partial Remission [ Time Frame: Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) [ Time Frame: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in Chest Expansion [ Time Frame: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) [ Time Frame: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline in Nocturnal Pain [ Time Frame: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    Nocturnal pain assessed by subjects using a Visual Analog Scale (VAS) of 0 - 100 mm (0 = no pain and 100 = worst possible pain).

  • Mean Change From Baseline in Swollen Joint Count for 44 Joints (SJC 44) [ Time Frame: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline in Tender Joint Count for 46 Joints (TJC 46) [ Time Frame: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire [ Time Frame: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit ] [ Designated as safety issue: No ]
    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).


Enrollment: 41
Study Start Date: February 2008
Study Completion Date: January 2011
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adalimumab
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
40 mg or 80 mg every other week, subcutaneous
Other Names:
  • ABT-D2E7
  • Humira
  • adalimumab

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00667355

Locations
Japan
Site Reference # / Investigator 46791
Aichi, Japan
Site Reference # / Investigator 46789
Fukui, Japan
Site Reference # / Investigator 46799
Fukuoka, Japan
Site Reference # / Investigator 46798
Fukuoka, Japan
Site Reference # / Investigator 46796
Hiroshima, Japan
Site Reference # / Investigator 46782
Hokkaido, Japan
Site Reference # / Investigator 7297
Hokkaido, Japan
Site Reference # / Investigator 46795
Hyogo, Japan
Site Reference # / Investigator 46797
Kagawa, Japan
Site Reference # / Investigator 46787
Kanagawa, Japan
Site Reference # / Investigator 46790
Nagano, Japan
Site Reference # / Investigator 46794
Osaka, Japan
Site Reference # / Investigator 46793
Osaka, Japan
Site Reference # / Investigator 46783
Saitama, Japan
Site Reference # / Investigator 46784
Saitama, Japan
Site Reference # / Investigator 46792
Shiga, Japan
Site Reference # / Investigator 46786
Tokyo, Japan
Site Reference # / Investigator 46785
Tokyo, Japan
Site Reference # / Investigator 46788
Toyama, Japan
Sponsors and Collaborators
Abbott
Eisai Co., Ltd.
Investigators
Study Director: Hideyuki Hashiba, BS Abbott
  More Information

No publications provided

Responsible Party: Abbott
ClinicalTrials.gov Identifier: NCT00667355     History of Changes
Other Study ID Numbers: M10-239
Study First Received: April 24, 2008
Results First Received: May 28, 2010
Last Updated: January 24, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Abbott:
Ankylosing Spondylitis

Additional relevant MeSH terms:
Spondylitis
Spondylitis, Ankylosing
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Spondylarthritis
Ankylosis
Joint Diseases
Arthritis
Adalimumab
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 20, 2014