A Study of Adalimumab in Japanese Subjects With Active Ankylosing Spondylitis

• Sponsor: Abbott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00667355
• Collaborator: Eisai Co., Ltd. (Industry)
• Enrollment: 41
• Locations: 19
• Arm: 1
• Duration (Months): 35
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Ankylosing Spondylitis	Biological: adalimumab	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Achieving Assessment in Ankylosing Spondylitis 20 (ASAS 20) at Week 12 [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.

Secondary Outcome Measures

1. Number of Subjects Achieving ASAS 20 [Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

   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.

2. Number of Subjects Achieving ASAS 50 [Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

   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.

3. Number of Subjects Achieving ASAS 70 [Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

   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.

4. Number of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50) [Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

   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.

5. Mean Change From Baseline in Patient's Global Assessment of Disease Activity [Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

   Subject's assessment of disease activity using a Visual Analog Scale (VAS) of 0 - 100 mm (0 = none and 100 = severe).

6. Mean Change From Baseline in Total Back Pain [Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

   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).

7. Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) [Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

   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.

8. Mean Change From Baseline in C-Reactive Protein (CRP) [Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

   CRP is a marker of inflammation and measured in mg/dL. A higher level is consistent with inflammation.

9. Number of Subjects Achieving Assessment in Ankylosing Spondylitis (ASAS) 5/6. [Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

   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]).

10. Number of Subjects Achieving Assessment in Ankylosing Spondylitis 40 (ASAS 40) [Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

    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.

11. Number of Subjects Achieving Assessment in Ankylosing Spondylitis Partial Remission [Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

    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.

12. Mean Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) [Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

    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.

13. Mean Change From Baseline in Chest Expansion [Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

    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.

14. Mean Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) [Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

    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).

15. Mean Change From Baseline in Nocturnal Pain [Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

    Nocturnal pain assessed by subjects using a Visual Analog Scale (VAS) of 0 - 100 mm (0 = no pain and 100 = worst possible pain).

16. Mean Change From Baseline in Swollen Joint Count for 44 Joints (SJC 44) [Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

    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).

17. Mean Change From Baseline in Tender Joint Count for 46 Joints (TJC 46) [Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

    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).

18. Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire [Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit]

    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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Site Reference # / Investigator 46791	Aichi		Japan
2	Site Reference # / Investigator 46789	Fukui		Japan
3	Site Reference # / Investigator 46798	Fukuoka		Japan
4	Site Reference # / Investigator 46799	Fukuoka		Japan
5	Site Reference # / Investigator 46796	Hiroshima		Japan
6	Site Reference # / Investigator 46782	Hokkaido		Japan
7	Site Reference # / Investigator 7297	Hokkaido		Japan
8	Site Reference # / Investigator 46795	Hyogo		Japan
9	Site Reference # / Investigator 46797	Kagawa		Japan
10	Site Reference # / Investigator 46787	Kanagawa		Japan
11	Site Reference # / Investigator 46790	Nagano		Japan
12	Site Reference # / Investigator 46793	Osaka		Japan
13	Site Reference # / Investigator 46794	Osaka		Japan
14	Site Reference # / Investigator 46783	Saitama		Japan
15	Site Reference # / Investigator 46784	Saitama		Japan
16	Site Reference # / Investigator 46792	Shiga		Japan
17	Site Reference # / Investigator 46785	Tokyo		Japan
18	Site Reference # / Investigator 46786	Tokyo		Japan
19	Site Reference # / Investigator 46788	Toyama		Japan

Sponsors and Collaborators

• Abbott
• Eisai Co., Ltd.

Investigators

• Study Director: Hideyuki Hashiba, BS, Abbott

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Abbott
• ClinicalTrials.gov Identifier: NCT00667355
• Other Study ID Numbers: M10-239
• First Posted: Apr 28, 2008
• Last Update Posted: Jan 26, 2012
• Last Verified: Jan 1, 2012

• Keywords provided by Abbott: Ankylosing Spondylitis
• Additional relevant MeSH terms: Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Adalimumab

Study Results

Participant Flow

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Period Title: Overall Study
STARTED	41
COMPLETED	30
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Overall Participants	41
Age, Customized (subjects) [Number]
<40 years	25
Between 40 and 65 years	16
>65 years	0
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.2 (12.17)
Sex: Female, Male (Count of Participants)
Female	9 22%
Male	32 78%
Region of Enrollment (subjects) [Number]
Japan	41

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Achieving Assessment in Ankylosing Spondylitis 20 (ASAS 20) at Week 12
Description	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.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

For all non-responder imputation (NRI) analyses, subjects with a missing value at a visit were imputed as a non-responder for that visit. Observed cases is based on a total of 40 subjects analyzed (vs. 41 subjects for the study and all other analysis sets) due to 1 subject who discontinued prior to Week 12.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Non-responder imputation (NRI), N = 41	30
Last Observation Carried Forward (LOCF), N = 41	30
Observed Cases, N = 40	30

2. Secondary Outcome

Title	Number of Subjects Achieving ASAS 20
Description	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.
Time Frame	Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on non-responder imputation (NRI), for which subjects with a missing value at a visit were imputed as a non-responder for that visit.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	30
Week 24	30
Week 48	32
Week 72	32
Week 96	27
Week 120	21
Final Visit	32

3. Secondary Outcome

Title	Number of Subjects Achieving ASAS 50
Description	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.
Time Frame	Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	23
Week 24	26
Week 48	26
Week 72	25
Week 96	19
Week 120	17
Final Visit	27

4. Secondary Outcome

Title	Number of Subjects Achieving ASAS 70
Description	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.
Time Frame	Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	13
Week 24	16
Week 48	18
Week 72	17
Week 96	15
Week 120	13
Final Visit	19

5. Secondary Outcome

Title	Number of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50)
Description	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.
Time Frame	Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	27
Week 24	26
Week 48	25
Week 72	28
Week 96	22
Week 120	18
Final Visit	29

6. Secondary Outcome

Title	Mean Change From Baseline in Patient's Global Assessment of Disease Activity
Description	Subject's assessment of disease activity using a Visual Analog Scale (VAS) of 0 - 100 mm (0 = none and 100 = severe).
Time Frame	Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on LOCF.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	-34.6
Week 24	-37.3
Week 48	-39.5
Week 72	-39.7
Week 96	-37.1
Week 120	-40.1
Final Visit	-40.6

7. Secondary Outcome

Title	Mean Change From Baseline in Total Back Pain
Description	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).
Time Frame	Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on LOCF.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	-35.6
Week 24	-37.0
Week 48	-38.6
Week 72	-39.3
Week 96	-36.4
Week 120	-39.2
Final Visit	-40.2

8. Secondary Outcome

Title	Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
Description	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.
Time Frame	Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on last observation carried forward (LOCF).

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	-19.4
Week 24	-20.5
Week 48	-21.9
Week 72	-22.2
Week 96	-22.1
Week 120	-21.8
Final Visit	-21.6

9. Secondary Outcome

Title	Mean Change From Baseline in C-Reactive Protein (CRP)
Description	CRP is a marker of inflammation and measured in mg/dL. A higher level is consistent with inflammation.
Time Frame	Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on LOCF.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	-1.2
Week 24	-1.3
Week 48	-1.4
Week 72	-1.3
Week 96	-1.4
Week 120	-1.3
Final Visit	-1.2

10. Secondary Outcome

Title	Number of Subjects Achieving Assessment in Ankylosing Spondylitis (ASAS) 5/6.
Description	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]).
Time Frame	Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	28
Week 24	29
Week 48	31
Week 72	28
Week 96	25
Week 120	20
Final Visit	29

11. Secondary Outcome

Title	Number of Subjects Achieving Assessment in Ankylosing Spondylitis 40 (ASAS 40)
Description	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.
Time Frame	Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	26
Week 24	26
Week 48	27
Week 72	28
Week 96	24
Week 120	18
Final Visit	26

12. Secondary Outcome

Title	Number of Subjects Achieving Assessment in Ankylosing Spondylitis Partial Remission
Description	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.
Time Frame	Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	15
Week 24	16
Week 48	17
Week 72	20
Week 96	15
Week 120	13
Final Visit	19

13. Secondary Outcome

Title	Mean Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
Description	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.
Time Frame	Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on LOCF.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	-0.4
Week 24	-0.5
Week 48	-0.6
Week 72	-0.5
Week 96	-0.6
Week 120	-0.7
Final Visit	-0.6

14. Secondary Outcome

Title	Mean Change From Baseline in Chest Expansion
Description	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.
Time Frame	Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on LOCF.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	0.7
Week 24	0.4
Week 48	0.8
Week 72	1.0
Week 96	0.6
Week 120	1.1
Final Visit	1.2

15. Secondary Outcome

Title	Mean Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
Description	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).
Time Frame	Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on LOCF.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	-1.0
Week 24	-1.1
Week 48	-1.3
Week 72	-1.1
Week 96	-1.4
Week 120	-1.4
Final Visit	-1.4

16. Secondary Outcome

Title	Mean Change From Baseline in Nocturnal Pain
Description	Nocturnal pain assessed by subjects using a Visual Analog Scale (VAS) of 0 - 100 mm (0 = no pain and 100 = worst possible pain).
Time Frame	Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on LOCF.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	-30.0
Week 24	-31.7
Week 48	-35.8
Week 72	-34.6
Week 96	-33.4
Week 120	-35.0
Final Visit	-35.3

17. Secondary Outcome

Title	Mean Change From Baseline in Swollen Joint Count for 44 Joints (SJC 44)
Description	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).
Time Frame	Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on LOCF.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	-1.1
Week 24	-1.1
Week 48	-1.1
Week 72	-1.3
Week 96	-1.2
Week 120	-1.2
Final Visit	-1.2

18. Secondary Outcome

Title	Mean Change From Baseline in Tender Joint Count for 46 Joints (TJC 46)
Description	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).
Time Frame	Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on LOCF.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
Week 12	-1.5
Week 24	-1.4
Week 48	-1.3
Week 72	-1.6
Week 96	-1.6
Week 120	-1.6
Final Visit	-1.6

19. Secondary Outcome

Title	Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
Description	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).
Time Frame	Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit

Outcome Measure Data

Analysis Population Description

Analysis is based on LOCF.

Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
Measure Participants	41
PCS Week 12	9.6
PCS Week 24	10.6
PCS Week 48	11.4
PCS Week 72	11.3
PCS Week 96	12.3
PCS Week 120	12.1
PCS Final Visit	12.6
MCS Week 12	7.0
MCS Week 24	7.0
MCS Week 48	6.1
MCS Week 72	6.7
MCS Week 96	5.8
MCS Week 120	6.1
MCS Final Visit	5.9

Adverse Events

Time Frame	All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
Arm/Group Title	Adalimumab
Arm/Group Description	Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
All Cause Mortality
	Adalimumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Adalimumab
	Affected / at Risk (%)	# Events
Total	6/41 (14.6%)
Blood and lymphatic system disorders
Thrombocytopenia	1/41 (2.4%)
Eye disorders
Cataract	2/41 (4.9%)
Gastrointestinal disorders
Periodontitis	1/41 (2.4%)
Infections and infestations
Intervertebral discitis	1/41 (2.4%)
Osteomyelitis	1/41 (2.4%)
Pneumonia	1/41 (2.4%)
Septic shock	1/41 (2.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/41 (2.4%)
Colon cancer	1/41 (2.4%)
Reproductive system and breast disorders
Adenomyosis	1/41 (2.4%)
Other (Not Including Serious) Adverse Events
	Adalimumab
	Affected / at Risk (%)	# Events
Total	41/41 (100%)
Eye disorders
Cataract	4/41 (9.8%)
Conjunctivitis allergic	3/41 (7.3%)
Gastrointestinal disorders
Diarrhoea	8/41 (19.5%)
Stomatitis	3/41 (7.3%)
Nausea	4/41 (9.8%)
General disorders
Injection site erythema	6/41 (14.6%)
Pyrexia	4/41 (9.8%)
Malaise	3/41 (7.3%)
Hepatobiliary disorders
Hepatic function abnormal	9/41 (22%)
Hepatic steatosis	3/41 (7.3%)
Infections and infestations
Nasopharyngitis	22/41 (53.7%)
Upper respiratory tract infection	8/41 (19.5%)
Pharyngitis	4/41 (9.8%)
Gastroenteritis	3/41 (7.3%)
Upper respiratory tract infection	7/41 (17.1%)
Influenza	4/41 (9.8%)
Rhinitis	3/41 (7.3%)
Injury, poisoning and procedural complications
Contusion	6/41 (14.6%)
Investigations
Weight increased	4/41 (9.8%)
C-reactive protein increased	3/41 (7.3%)
Metabolism and nutrition disorders
Hyperlipidaemia	3/41 (7.3%)
Musculoskeletal and connective tissue disorders
Ankylosing spondylitis	6/41 (14.6%)
Back pain	4/41 (9.8%)
Arthralgia	3/41 (7.3%)
Myalgia	3/41 (7.3%)
Nervous system disorders
Headache	5/41 (12.2%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation	8/41 (19.5%)
Pharyngolaryngeal pain	3/41 (7.3%)
Skin and subcutaneous tissue disorders
Rash	5/41 (12.2%)
Dermatitis contact	3/41 (7.3%)
Erythema	3/41 (7.3%)
Vascular disorders
Hypertension	3/41 (7.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Disclosure agreements vary; the Medical Institution shall not disclose any material/information disclosed by Abbott Japan in connection with the Clinical Research or information obtained by conducting the Clinical Research to third parties without Abbott Japan's prior written approval. When Medical Institution intends to publish information obtained by conducting Clinical Research, Institution shall obtain Abbott Japan's prior written approval.