Efficacy and Safety of Adalimumab in Adult Chinese Subjects With Active Ankylosing Spondylitis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Abbott
ClinicalTrials.gov Identifier:
NCT01114880
First received: February 5, 2010
Last updated: November 22, 2011
Last verified: November 2011
  Purpose

Study of the efficacy and safety of adalimumab compared with placebo in adult Chinese participants with ankylosing spondylitis (AS) who have had an inadequate response to or who are intolerant to one or more nonsteroidal anti-inflammatory drugs (NSAIDs)


Condition Intervention Phase
Ankylosing Spondylitis
Biological: adalimumab
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Placebo Controlled, Multicenter, Efficacy and Safety Study of Adalimumab in Adult Chinese Subjects With Active Ankylosing Spondylitis

Resource links provided by NLM:


Further study details as provided by Abbott:

Primary Outcome Measures:
  • Number of Participants Meeting the Assessment of Spondyloarthritis International Society (ASAS) ASAS20 Response Criteria [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    ASAS20 responder had improvement of 20% or more and absolute improvement of at least 10 units (on a scale of 0 [least] to 100 [worst]) from Baseline in at least 3 of the following 4 domains, with absence of deterioration (change for worse of at least 20% and net worsening of at least 10 units) in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Bath Ankylosing Spondylitis Functional Index (BASFI); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores).


Secondary Outcome Measures:
  • Number of Participants Meeting the ASAS20 Response Criteria [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    ASAS20 responder had improvement of 20% or more and absolute improvement of at least 10 units (on a scale of 0 [least] to 100 [worst]) from Baseline in at least 3 of the following 4 domains, with absence of deterioration (change for worse of at least 20% and net worsening of at least 10 units) in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Bath Ankylosing Spondylitis Functional Index (BASFI); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores).

  • Number of Participants Meeting the ASAS40 Response Criteria [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    An ASAS40 responder had improvement of 40% or more and absolute improvement of 20 units or more (on a scale of 0 [least] to 100 [worst]) from Baseline in at least 3 of the 4 domains identified above for the ASAS20. In addition, there must have been an absence of deterioration in the potential remaining domain, where deterioration was defined as a net worsening of greater than 0 units (on a scale of 0 to 100).

  • Number of Participants Meeting the ASAS40 Response Criteria [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    An ASAS40 responder had improvement of 40% or more and absolute improvement of 20 units or more (on a scale of 0 [least] to 100 [worst]) from Baseline in at least 3 of the 4 domains identified above for the ASAS20. In addition, there must have been an absence of deterioration in the potential remaining domain, where deterioration was defined as a net worsening of greater than 0 units (on a scale of 0 to 100).

  • Number of Participants Meeting the ASAS5/6 Response Criteria [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    An ASAS5/6 responder had an improvement from Baseline of 20% or more in 5 of the following 6 domains: Patient's Global Assessment of Disease Activity; pain as measured by the Total Back Pain visual analog scale (VAS); function as measured by the Bath Ankylosing Spondylitis Functional Index (BASFI); inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores); spinal mobility (lateral lumbar flexion from Bath Ankylosing Spondylitis Metrology Index [BASMI]); and acute phase reactant (high-sensitivity C-reactive protein).

  • Number of Participants Meeting the ASAS5/6 Response Criteria [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    An ASAS5/6 responder had an improvement from Baseline of 20% or more in 5 of the following 6 domains: Patient's Global Assessment of Disease Activity; pain as measured by the Total Back Pain visual analog scale (VAS); function as measured by the Bath Ankylosing Spondylitis Functional Index (BASFI); inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores); spinal mobility (lateral lumbar flexion from Bath Ankylosing Spondylitis Metrology Index [BASMI]); and acute phase reactant (high-sensitivity C-reactive protein).

  • Number of Participants With ASAS Partial Remission [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Participants were classified as having achieved ASAS partial remission if they had a value of less than 20 on a scale from 0 (normal/none) to 100 (most severe) in each of 4 domains: Patient's Global Assessment of Disease Activity; pain as measured by the Total Back Pain visual analog scale (VAS); function as measured by the Bath Ankylosing Spondylitis Functional Index (BASFI); and inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores).

  • Number of Participants With ASAS Partial Remission [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Participants were classified as having achieved ASAS partial remission if they had a value of less than 20 on a scale from 0 (normal/none) to 100 (most severe) in each of 4 domains: Patient's Global Assessment of Disease Activity; pain as measured by the Total Back Pain visual analog scale (VAS); function as measured by the Bath Ankylosing Spondylitis Functional Index (BASFI); and inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores).

  • Change From Baseline in Patient Global Assessment of Disease Activity [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Participants assessed their disease activity during the preceding week using a 100 millimeter (mm) visual analog scale, with responses ranging from no activity (0) to severe activity (100).

  • Change From Baseline in Patient Global Assessment of Disease Activity [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Participants assessed their disease activity during the preceding week using a 100 millimeter (mm) visual analog scale, with responses ranging from no activity (0) to severe activity (100).

  • Change From Baseline in Total Back Pain Score [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Participants assessed their total back pain within the preceding week using a total back pain 100 mm visual analog scale, with responses ranging from no pain (0) to most severe pain (100).

  • Change From Baseline in Total Back Pain Score [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Participants assessed their total back pain within the preceding week using a total back pain 100 mm visual analog scale, with responses ranging from no pain (0) to most severe pain (100).

  • Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Participants assessed their ability to perform 10 selected activities (e.g., putting on socks or tights without help or aids, bending forward from the waist to pick up a pen from the floor without an aid) during the preceding week. Responses ranged from 0 (easy) to 100 (impossible). The BASFI score is the average of the 10 responses and has a possible minimum value of 0 and a possible maximum value of 100.

  • Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Participants assessed their ability to perform 10 selected activities (e.g., putting on socks or tights without help or aids, bending forward from the waist to pick up a pen from the floor without an aid) during the preceding week. Responses ranged from 0 (easy) to 100 (impossible). The BASFI score is the average of the 10 responses and has a possible minimum value of 0 and a possible maximum value of 100.

  • Change From Baseline in Inflammation Score [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The Inflammation score is the mean of the 10-cm visual analog scale scores from the 2 morning stiffness-related BASDAI questions: "How would you describe the overall level of morning stiffness you have had from the time you wake up?", with response ranging from none to very severe; and "How long does your morning stiffness last from the time you wake up?", with response ranging from 0 hours to 2 or more hours.

  • Change From Baseline in Inflammation Score [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The Inflammation score is the mean of the 10-cm visual analog scale scores from the 2 morning stiffness-related BASDAI questions: "How would you describe the overall level of morning stiffness you have had from the time you wake up?", with response ranging from none to very severe; and "How long does your morning stiffness last from the time you wake up?", with response ranging from 0 hours to 2 or more hours.

  • Number of Participants Meeting the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI) BASDAI50 Response Criteria [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    A BASDAI50 responder had at least a 50% improvement from Baseline in BASDAI score. In the BASDAI, participants use a 10-centimeter visual analog scale to answer 6 questions pertaining to symptoms experienced in the preceding week (e.g., How would you describe the overall level of fatigue/tiredness you have experienced? How long does your morning stiffness last from the time you wake up?) Responses range from "none" to "very severe" or from 0 hours to 2 or more hours for morning stiffness. The score is calculated as 0.2 (Q1 + Q2 + Q3 + Q4 + Q5/2 + Q6/2).

  • Number of Participants Meeting the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI) BASDAI50 Response Criteria [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    A BASDAI50 responder had at least a 50% improvement from Baseline in BASDAI score. In the BASDAI, participants use a 10-centimeter visual analog scale to answer 6 questions pertaining to symptoms experienced in the preceding week (e.g., How would you describe the overall level of fatigue/tiredness you have experienced? How long does your morning stiffness last from the time you wake up?) Responses range from "none" to "very severe" or from 0 hours to 2 or more hours for morning stiffness. The score is calculated as 0.2 (Q1 + Q2 + Q3 + Q4 + Q5/2 + Q6/2).

  • Change From Baseline in High-sensitivity C-Reactive Protein (Hs-CRP) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Elevation of hs-CRP is a nonspecific marker of inflammation. Values above 5 milligrams/liter (mg/L) were considered abnormally high. Decrease in level of hs-CRP indicates reduction in inflammation.

  • Change From Baseline in High-sensitivity C-Reactive Protein (Hs-CRP) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Elevation of hs-CRP is a nonspecific marker of inflammation. Values above 5 milligrams/liter (mg/L) were considered abnormally high. Decrease in level of hs-CRP indicates reduction in inflammation.

  • Change From Baseline in 36-item Short Form Questionnaire Version 2 (SF-36v2) Physical Component Summary Score [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The SF-36 questionnaire, version 2, consists of 36 general health questions with 2 components, physical and mental. For each component, a transformed summary score is calculated using 8 sub-domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scores range from 0 to 100. Higher scores indicate a better health state.

  • Change From Baseline in 36-item Short Form Questionnaire Version 2 (SF-36v2) Physical Component Summary Score [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The SF-36 questionnaire, version 2, consists of 36 general health questions with 2 components, physical and mental. For each component, a transformed summary score is calculated using 8 sub-domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scores range from 0 to 100. Higher scores indicate a better health state.


Enrollment: 344
Study Start Date: January 2010
Study Completion Date: February 2011
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Blinded placebo from Week 0 to Week 10, open-label adalimumab from Week 12 to Week 24.
Biological: adalimumab
Prefilled syringe, 40 mg/0.8 mL administered subcutaneously every other week
Other Names:
  • ABT-D2E7
  • adalimumab
  • Humira
Other: placebo
Prefilled syringe, matching placebo administered subcutaneously every other week
Experimental: Adalimumab
Blinded adalimumab from Week 0 to Week 10, open-label adalimumab from Week 12 to Week 24.
Biological: adalimumab
Prefilled syringe, 40 mg/0.8 mL administered subcutaneously every other week
Other Names:
  • ABT-D2E7
  • adalimumab
  • Humira

Detailed Description:

Adults with active ankylosing spondylitis (AS) were randomized in a 2:1 ratio to receive treatment with adalimumab 40 mg every other week (eow) or matching placebo, given subcutaneously (SC), in the 12-week double-blind (DB) phase. Randomized participants received one SC injection of the appropriate DB study medication (adalimumab 40 mg or matching placebo) at Week 0 and then eow until Week 10. Participants who completed the DB phase could enter the 12-week open-label (OL) phase, during which all participants received treatment with adalimumab 40 mg eow, starting at Weeks 12 through 22. No study drug was administered or injected at the final study visit (Week 24). A follow-up visit occurred 70 days after the last dose of study drug (in DB or OL phases) to obtain information on any ongoing or new adverse events (AEs).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 through 65 years
  • Has a diagnosis of ankylosing spondylitis (AS) based on the Modified New York Criteria
  • Has active AS, as defined by fulfillment of at least 2 of the following 3 conditions at both Screening and Baseline visits:

    • BASDAI score at least 4 cm
    • Total back pain on a visual analog scale (VAS) at least 40 mm
    • Morning stiffness at least 1 hr
  • Has inadequate response to or intolerance to one or more non-steroidal anti-inflammatory drugs (NSAIDs) as defined by the Investigator

Exclusion Criteria:

  • Has total spinal ankylosis (bamboo spine)
  • Has undergone spinal surgery or joint surgery involving joints assessed within 2 months prior to Baseline
  • Has extra-articular manifestations (i.e., psoriasis, uveitis, inflammatory bowel disease) that is not clinically stable, as defined by the Investigator's best clinical judgment, for at least 28 days prior to Baseline
  • Has received intra-articular joint injection(s), spinal or paraspinal injection(s) with corticosteroids within 28 days prior to Baseline
  • Has prior exposure to any biologic therapy with potential therapeutic impact on AS, including anti-TNF (tumor necrosis factor) therapy
  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: NCT01114880

Locations
China, Anhui
Site Reference ID/Investigator# 24054
Hefei, Anhui, China, 230022
China
Site Reference ID/Investigator# 24055
Beijing, China, 100032
Site Reference ID/Investigator# 24052
Beijing, China, 100853
Site Reference ID/Investigator# 25522
Beijing, China, 100029
Site Reference ID/Investigator# 24056
Guangzhou, China, 510630
Site Reference ID/Investigator# 24243
Hangzhou, China, 310009
Site Reference ID/Investigator# 24058
Shanghai, China, 200003
Site Reference ID/Investigator# 24053
Shanghai, China, 200001
Site Reference ID/Investigator# 24057
Xi'an, China, 710032
Sponsors and Collaborators
Abbott
Investigators
Study Director: Aileen Pangan Abbott
  More Information

No publications provided

Responsible Party: Abbott
ClinicalTrials.gov Identifier: NCT01114880     History of Changes
Other Study ID Numbers: M11-991
Study First Received: February 5, 2010
Results First Received: September 29, 2011
Last Updated: November 22, 2011
Health Authority: China: Food and Drug Administration

Keywords provided by Abbott:
ankylosing spondylitis
China

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

ClinicalTrials.gov processed this record on July 29, 2014