Clinical trial NCT00195819: Safety and Efficacy of Adalimumab in Patients With Active Ankylosing Spondylitis
Official title: A Phase 3, Multicenter Study of the Safety and Efficacy of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Active Ankylosing Spondylitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ankylosing Spondylitis
Keywords: ankylosing spondylitis
adalimumab
Lead sponsor: Abbott
Sponsor class: INDUSTRY
First posted: 2005-09-20
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to assess the safety and clinical efficacy of adalimumab in subjects with active ankylosing spondylitis


Eligibility criteria: Inclusion Criteria:

* Subject was age 18 or older and in relatively good health (Investigator discretion) with a recent stable medical history.
* Subject met the definition of AS based on the Modified New York Criteria.
* Subject had an inadequate response to or intolerance to one or more NSAIDs as defined by the Investigator

Exclusion Criteria:

* Subject had previously received anti-TNF therapy.
* Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study
* Female subject who is pregnant or breast-feeding or considering becoming pregnant

Primary outcomes:
measure: Number of Subjects With a Reduction in Signs and Symptoms as Measured by Assessments of Ankylosing Spondylitis (ASAS) 20 Response at Week 12
timeFrame: Week 12
measure: Mean Change in the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) Compared Against a Historical Control Group (Outcomes in Ankylosing Spondylitis International Study [OASIS]) Using the ANCOVA Model Adjusting for Baseline mSASSS Score
timeFrame: Baseline and Week 104
Secondary outcomes:
measure: Number of Subjects With a Reduction of Signs and Symptoms as Measured in Assessments of Ankylosing Spondylitis (ASAS) 20 - Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Number of Subjects With a Reduction of Signs and Symptoms as Measured by Assessments in Ankylosing Spondylitis (ASAS) ASAS 50 Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Number of Subjects With a Reduction of Signs and Symptoms as Measured in Assessments of Ankylosing Spondylitis (ASAS) ASAS 70 Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in Patient's Global Assessment of Disease Activity in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 36, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Number of Subjects With a Reduction of Signs and Symptoms as Measured in Patient's Global Assessment of Disease Activity (an Individual Component of ASAS 20) Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in the Bath Ankylosing Spondylitis Functional Index (BASFI) in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, 244, and 260
measure: BASFI (an Individual Component of ASAS 20) Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in Total Back Pain Visual Analog Scale (VAS) in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Total Back Pain (an Individual Component of ASAS 20) Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 128, 152, 180, 208, 220, 232, 244, and 260
measure: Mean Change in Inflammation (Mean of BASDAI Questions 5 and 6) in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Inflammation (Individual Component of ASAS 20) (Mean of BASDAI Questions 5 and 6) Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Number of Subjects With a Reduction of Signs and Symptoms as Measured in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 20 Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Number of Subjects With a Reduction of Signs and Symptoms as Measured in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Number of Subjects With a Reduction of Signs and Symptoms as Measured in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 70 Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in BASDAI in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in C-Reactive Protein (CRP) (mg/dL) in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Number of Subjects With a Disease Controlling Clinical Response From Adalimumab as Measured in Assessments of Ankylosing Spondylitis (ASAS) 40 - Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244 and 260
measure: Number of Subjects With a Disease Controlling Clinical Response From Adalimumab as Measured in Assessments of Ankylosing Spondylitis Ankylosing Spondylitis (ASAS) 5/6 in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 16, 20, 24, 30, 36, 42, 48, 52, 64, 76, 88, 104, 116, 128, 140, 156, 168, 180, 192, 208, 220, 232, 244, and 260
measure: Number of Subjects With a Disease Controlling Clinical Response From Adalimumab as Measured in Partial Remission Response in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in the Bath Ankylosing Spondylitis Metrology Index (BASMI) in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in Edmonton Ankylosing Spondylitis Metrology Index (EDASMI) in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 52, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in Chest Expansion (CE) in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 52,104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260
measure: Mean Change in the Bath Ankylosing Spondylitis Global Index (BAS-G) in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in Swollen Joint Count for 44 Joints (44 SJC) in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 36, 52, 76, 104, 128, 156, 180, 208, 232, and 260
measure: Mean Change From Baseline in the Tender Joint Count for 46 Joints (TJC 46) in Subjects With Adalimumab Exposure Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 36, 52, 76, 104, 128, 156, 180, 208, 232, and 260
measure: Mean Change in Physician's Global Assessment of Disease Activity in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in Nocturnal Pain in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Baseline and at Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260
measure: Mean Change in the SF-36 Health Survey Index Physical Component Summary [PCS] Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260
measure: Number of Subjects With SF-36 Physical Component Summary (PCS) of Minimal Clinically Important Difference (MCID) Response Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260
measure: Mean Change in the SF-36 Health Survey Index Mental Component Summary [MCS] Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260
measure: Number of Subjects With SF-36 Mental Component Summary (MCS) of Minimal Clinically Important Difference (MCID) Response Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260
measure: Mean Change in Health Utilities Index-3 (HUI-3) Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 24, 52, 104, 128, 156, 180, 208, 232, and 260
measure: Mean Change in the Ankylosing Spondylitis Quality of Life Questionaire (ASQoL) in Subjects Through Week 260 of Adalimumab Exposure
timeFrame: Baseline and at Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260
measure: Number of Subjects With Ankylosing Spondylitis Quality of Life Questionaire (ASQoL) MCID Response (MCID <= -1.8 Points) Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260
measure: Number of Subjects Achieving the Patient Acceptable Symptoms State Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260
measure: Mean Change From Baseline in Serum Matrix Metalloproteinase-3 (MMP-3) in Subjects Treated With Any Dose of Adalimumab Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change From Baseline in Urine Type II Collagen C Telopeptide (CTX-II) in Subjects Treated With Any Dose of Adalimumab Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change From Baseline in Serum Type I Collagen N-telopeptide (NTx) in Subjects Treated With Any Dose of Adalimumab Through Week 260 of Adalimumab Exposure
timeFrame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in Spinal Spondyloarthritis Research Consortium of Canada (S.P.A.R.C.C.) Magnetic Resonance Imaging (MRI) Index of Disease Activity Score at Weeks 12 and 52 of Adalimumab Exposure
timeFrame: Week 12 and Week 52
measure: Mean Change in Sacroiliac (SI) Spondyloarthritis Research Consortium of Canada (S.P.A.R.C.C.) Magnetic Resonance Imaging (MRI) Index of Disease Activity Score at Weeks 12 and 52 of Adalimumab Exposure
timeFrame: Weeks 12 and 52
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Site Ref # / Investigator 74
state: Alberta
city: Edmonton
country: Canada
facility: Site Ref # / Investigator 70
state: Alberta
city: Vancouver
country: Canada
facility: Site Ref # / Investigator 79
state: British Columbia
city: Winnipeg
country: Canada
facility: Site Ref # / Investigator 64
state: Manitoba
city: St. John's
country: Canada
facility: Site Ref # / Investigator 78
state: Newfoundland and Labrador
city: Toronto
country: Canada
facility: Site Ref # / Investigator 75
state: Ontario
city: Toronto
country: Canada
facility: Site Ref # / Investigator 63
state: Ontario
city: Toronto
country: Canada
facility: Site Ref # / Investigator 62
state: Ontario
city: Saskatoon
country: Canada
facility: Site Ref # / Investigator 77
state: Saskatchewan
Study officials:
References:
citation: Revicki DA, Rentz AM, Luo MP, Wong RL. Psychometric characteristics of the short form 36 health survey and functional assessment of chronic illness Therapy-Fatigue subscale for patients with ankylosing spondylitis. Health Qual Life Outcomes. 2011 May 22;9:36. doi: 10.1186/1477-7525-9-36.
citation: van der Heijde D, Salonen D, Weissman BN, Landewe R, Maksymowych WP, Kupper H, Ballal S, Gibson E, Wong R; Canadian (M03-606) study group; ATLAS study group. Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther. 2009;11(4):R127. doi: 10.1186/ar2794. Epub 2009 Aug 24.
citation: Lambert RG, Salonen D, Rahman P, Inman RD, Wong RL, Einstein SG, Thomson GT, Beaulieu A, Choquette D, Maksymowych WP. Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2007 Dec;56(12):4005-14. doi: 10.1002/art.23044.