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

Ankylosing Spondylitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01114880
• Other study ID #: M11-991
• Status: Completed
• Phase: Phase 3
• First received: February 5, 2010
• Last updated: November 22, 2011
• Start date: January 2010
• Est. completion date: February 2011

Study information

• Verified date: November 2011
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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)

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 344
• Est. completion date: February 2011
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ankylosing Spondylitis
• Spondylitis
• Spondylitis, Ankylosing

Intervention

Biological:
• adalimumab
Prefilled syringe, 40 mg/0.8 mL administered subcutaneously every other week

Other:
• placebo
Prefilled syringe, matching placebo administered subcutaneously every other week

Locations

Country	Name	City	State
China	Site Reference ID/Investigator# 24052	Beijing
China	Site Reference ID/Investigator# 24055	Beijing
China	Site Reference ID/Investigator# 25522	Beijing
China	Site Reference ID/Investigator# 24056	Guangzhou
China	Site Reference ID/Investigator# 24243	Hangzhou
China	Site Reference ID/Investigator# 24054	Hefei	Anhui
China	Site Reference ID/Investigator# 24053	Shanghai
China	Site Reference ID/Investigator# 24058	Shanghai
China	Site Reference ID/Investigator# 24057	Xi'an

Sponsors (1)

Lead Sponsor	Collaborator
Abbott

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Meeting the Assessment of Spondyloarthritis International Society (ASAS) ASAS20 Response Criteria	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).	Week 12	No
Secondary	Number of Participants Meeting the ASAS20 Response Criteria	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).	Week 24	No
Secondary	Number of Participants Meeting the ASAS40 Response Criteria	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).	Week 12	No
Secondary	Number of Participants Meeting the ASAS40 Response Criteria	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).	Week 24	No
Secondary	Number of Participants Meeting the ASAS5/6 Response Criteria	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).	Week 12	No
Secondary	Number of Participants Meeting the ASAS5/6 Response Criteria	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).	Week 24	No
Secondary	Number of Participants With ASAS Partial Remission	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).	Week 12	No
Secondary	Number of Participants With ASAS Partial Remission	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).	Week 24	No
Secondary	Change From Baseline in Patient Global Assessment of Disease Activity	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).	Baseline and Week 12	No
Secondary	Change From Baseline in Patient Global Assessment of Disease Activity	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).	Baseline and Week 24	No
Secondary	Change From Baseline in Total Back Pain Score	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).	Baseline and Week 12	No
Secondary	Change From Baseline in Total Back Pain Score	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).	Baseline and Week 24	No
Secondary	Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score	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.	Baseline and Week 12	No
Secondary	Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score	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.	Baseline and Week 24	No
Secondary	Change From Baseline in Inflammation Score	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.	Baseline and Week 12	No
Secondary	Change From Baseline in Inflammation Score	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.	Baseline and Week 24	No
Secondary	Number of Participants Meeting the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI) BASDAI50 Response Criteria	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).	Week 12	No
Secondary	Number of Participants Meeting the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI) BASDAI50 Response Criteria	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).	Week 24	No
Secondary	Change From Baseline in High-sensitivity C-Reactive Protein (Hs-CRP)	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.	Baseline and Week 12	No
Secondary	Change From Baseline in High-sensitivity C-Reactive Protein (Hs-CRP)	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.	Baseline and Week 24	No
Secondary	Change From Baseline in 36-item Short Form Questionnaire Version 2 (SF-36v2) Physical Component Summary Score	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.	Baseline and Week 12	No
Secondary	Change From Baseline in 36-item Short Form Questionnaire Version 2 (SF-36v2) Physical Component Summary Score	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.	Baseline and Week 24	No