Clinical trial NCT00085644: Human Anti-tumor Necrosis Factor (TNF) Monoclonal Antibody Adalimumab in Subjects 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
Lead sponsor: Abbott
Sponsor class: INDUSTRY
First posted: 2004-06-16
Enrollment: 315
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 objective of this study was to evaluate the safety and efficacy of adalimumab 40 mg given every other week (eow) in subjects with active ankylosing spondylitis (AS) who have had an inadequate response to, or who are intolerant to, treatment with at least 1 nonsteroidal anti-inflammatory drug (NSAID) and who may have also failed treatment with at least 1 disease-modifying antirheumatic drug (DMARD).


Eligibility criteria: Inclusion Criteria:

* Subjects must be \>= 18 years of age
* meet Modified NY Criteria definition of ankylosing spondylitis (AS)
* have diagnosis of active AS based on protocol specified criteria
* inadequate response or intolerance to \>= 1 nonsteroidal antiinflammatory drug (NSAID)
* be able and willing to learn to self-administer subcutaneous (SC) injections

Exclusion Criteria:

* Active tuberculosis, listeriosis,or hepatitis B, or any history of hepatitis C
* History of demyelinating disease, multiple sclerosis, cancer, or lymphoproliferative disease
* Previous anti-tumor necrosis factor therapy
* Treatment with disease-modifying antirheumatic drugs (DMARDs - other than methotrexate, hydroxychloroquine, and sulfasalazine)
* Treatment with intra-articular corticosteroid joint injections within 4 weeks of study dosing
* Biologic or investigational therapy within 6 weeks of study dosing
* Treatment with intravenous (IV) antibiotics within 30 days of study dosing
* Treatment with oral antibiotics within 14 days of study dosing

Primary outcomes:
measure: Number of Responders With a Reduction of Signs and Symptoms of Ankylosing Spondylitis (AS) as Measured With ASAS International Working Group Response Criteria (ASAS 20).
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: 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 in Assessments of Ankylosing Spondylitis (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) 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: Baseline, 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 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: Baseline, 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 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: Baseline, 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 Total Back Pain (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 Inflammation (Mean of BASDAI Questions 5 and 6) in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Baseline, 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 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: Baseline, 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: Baseline, 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, 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 by ASAS 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: Baseline, Weeks 12, 24, 52, 76, 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: Baseline, Weeks 12, 24, 52, 76, 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: Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in the Bath Ankylosing Spondylitis Global Index (BAS-G) in Subjects With Adalimumab Exposure Through Week 260
timeFrame: Baseline, 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: Baseline, Weeks 12, 24, 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
timeFrame: Baseline, Weeks 12, 24, 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: Baseline, 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: Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260
measure: Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 260 of Adalimumab Exposure
timeFrame: Baseline, 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: Baseline, 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: Baseline, 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: Baseline, 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, 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
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: San Francisco
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Boise
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Portland
country: United States
state: Maine
city: Baltimore,
country: United States
state: Maryland
city: Wheaton
country: United States
state: Maryland
city: Omaha
country: United States
state: Nebraska
city: Lebanon
country: United States
state: New Hampshire
city: Albany
country: United States
state: New York
city: Oklahoma City
country: United States
state: Oklahoma
city: Duncansville
country: United States
state: Pennsylvania
city: West Reading
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Seattle
country: United States
state: Washington
Study officials:
affiliation: Abbott
name: Laura Redden, MD, PhD
role: STUDY_DIRECTOR
References:
citation: van der Heijde D, Breban M, Halter D, DiVittorio G, Bratt J, Cantini F, Kary S, Pangan AL, Kupper H, Rathmann SS, Sieper J, Mease PJ. Maintenance of improvement in spinal mobility, physical function and quality of life in patients with ankylosing spondylitis after 5 years in a clinical trial of adalimumab. Rheumatology (Oxford). 2015 Jul;54(7):1210-9. doi: 10.1093/rheumatology/keu438. Epub 2014 Dec 25.
citation: Kimel M, Revicki D, Rao S, Fryback D, Feeny D, Harnam N, Thompson C, Cifaldi M. Norms-based assessment of patient-reported outcomes associated with adalimumab monotherapy in patients with ankylosing spondylitis. Clin Exp Rheumatol. 2011 Jul-Aug;29(4):624-32. Epub 2011 Aug 31.
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: Reilly MC, Gooch KL, Wong RL, Kupper H, van der Heijde D. Validity, reliability and responsiveness of the Work Productivity and Activity Impairment Questionnaire in ankylosing spondylitis. Rheumatology (Oxford). 2010 Apr;49(4):812-9. doi: 10.1093/rheumatology/kep457. Epub 2010 Jan 25.
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: van der Heijde DM, Revicki DA, Gooch KL, Wong RL, Kupper H, Harnam N, Thompson C, Sieper J; ATLAS Study Group. Physical function, disease activity, and health-related quality-of-life outcomes after 3 years of adalimumab treatment in patients with ankylosing spondylitis. Arthritis Res Ther. 2009;11(4):R124. doi: 10.1186/ar2790. Epub 2009 Aug 17.
citation: van der Heijde D, Schiff MH, Sieper J, Kivitz AJ, Wong RL, Kupper H, Dijkmans BA, Mease PJ, Davis JC Jr; ATLAS Study Group. Adalimumab effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: long-term results from the ATLAS trial. Ann Rheum Dis. 2009 Jun;68(6):922-9. doi: 10.1136/ard.2007.087270. Epub 2008 Aug 13.
citation: Dougados M, Luo MP, Maksymowych WP, Chmiel JJ, Chen N, Wong RL, Davis JC Jr, van der Heijde D; ATLAS STUDY GROUP. Evaluation of the patient acceptable symptom state as an outcome measure in patients with ankylosing spondylitis: data from a randomized controlled trial. Arthritis Rheum. 2008 Apr 15;59(4):553-60. doi: 10.1002/art.23527.
citation: van der Heijde D, Pangan AL, Schiff MH, Braun J, Borofsky M, Torre J, Davis JC Jr, Wong RL, Kupper H, Collantes E; ATLAS Study Group. Adalimumab effectively reduces the signs and symptoms of active ankylosing spondylitis in patients with total spinal ankylosis. Ann Rheum Dis. 2008 Sep;67(9):1218-21. doi: 10.1136/ard.2007.082529. Epub 2007 Dec 4.