A Phase 3 Multicenter Study of the Safety and Efficacy of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Active Ankylosing Spondylitis

Abbott0 sites315 target enrollmentJanuary 2004

ConditionsAnkylosing Spondylitis

Overview

Phase: Phase 3
Intervention: Not specified
Conditions: Ankylosing Spondylitis
Sponsor: Abbott
Enrollment: 315
Primary Endpoint: 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).
Status: Completed
Last Updated: 15 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

January 2004

End Date

July 2009

Last Updated

15 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Abbott

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

Outcomes

Primary Outcomes

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).

Time Frame: Week 12

ASAS 20 responders - improvement of \>=20% and absolute improvement of \>=10 units from Baseline in a visual analog scale (VAS) for \>=3 of 4 domains; Patient's Global Assessment of disease activity VAS (0 \[none\]-100 \[severe\]), Total Back Pain VAS (0 \[no pain\]-100 \[severe\]), BASFI VAS (0 \[easy\]-100\[impossible\]); and Inflammation VAS (0 \[none\]-10 \[very severe\]) and absence of deterioration in the potential remaining domain, defined as a worsening of \>=20% and a net worsening of \>=10 units. Applied to each scale and not to an overall global scale.

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

Time Frame: Week 104

Radiographic progression was based on change in mSASSS scoring (comparison of the means) from double-blind Baseline visit to Week 104. The mSASSS is the sum of the lumbar and cervical spine score ( 0 \[no change\] to 72 \[progression\]), derived from scoring the anterior site of the lumbar spine (T12 to S1) and the cervical spine (C2 to T1) as either 0 (normal), 1 (erosion, sclerosis, or squaring), 2 (syndesmophyte), 3 (bridging syndesmophyte), or N (vertebral body not evaluable). Data from NCT00195819 was compared with data from AS patients in OASIS.

Secondary Outcomes

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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in Patient's Global Assessment of Disease Activity in Subjects With Adalimumab Exposure Through Week 260(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in the Bath Ankylosing Spondylitis Functional Index (BASFI) in Subjects With Adalimumab Exposure Through Week 260(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in Total Back Pain Visual Analog Scale (VAS) in Subjects With Adalimumab Exposure Through Week 260(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in Inflammation (Mean of BASDAI Questions 5 and 6) in Subjects With Adalimumab Exposure Through Week 260(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in BASDAI in Subjects With Adalimumab Exposure Through Week 260(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in C-Reactive Protein (CRP) (mg/dL) in Subjects With Adalimumab Exposure Through Week 260(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in the Bath Ankylosing Spondylitis Metrology Index (BASMI) in Subjects With Adalimumab Exposure Through Week 260(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in Chest Expansion (CE) in Subjects With Adalimumab Exposure Through Week 260 [(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Subjects With Adalimumab Exposure Through Week 260(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in the Bath Ankylosing Spondylitis Global Index (BAS-G) in Subjects With Adalimumab Exposure Through Week 260(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in Swollen Joint Count for 44 Joints (44 SJC) in Subjects With Adalimumab Exposure Through Week 260(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260)
Mean Change From Baseline in the Tender Joint Count for 46 Joints (TJC 46) in Subjects With Adalimumab Exposure Through Week 260(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260)
Mean Change in Physician's Global Assessment of Disease Activity in Subjects With Adalimumab Exposure Through Week 260(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in Nocturnal Pain in Subjects With Adalimumab Exposure Through Week 260(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 260 of Adalimumab Exposure(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260)
Number of Subjects With SF-36 Physical Component Summary (PCS) of Minimal Clinically Important Difference (MCID) Response Through Week 260 of Adalimumab Exposure(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260)
Mean Change in the SF-36 Health Survey Index Mental Component Summary (MCS) Through Week 260 of Adalimumab Exposure(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260)
Number of Subjects With SF-36 Mental Component Summary (MCS) of Minimal Clinically Important Difference (MCID) Response Through Week 260 of Adalimumab Exposure(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260)
Mean Change in Health Utilities Index-3 (HUI-3) Through Week 260 of Adalimumab Exposure(Baseline, Weeks 24, 52, 104, 128, 156, 180, 208, 232, and 260)
Mean Change in the Ankylosing Spondylitis Quality of Life Questionaire (ASQoL) in Subjects Through Week 260 of Adalimumab Exposure(Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260)
Number of Subjects With Ankylosing Spondylitis Quality of Life Questionaire (ASQoL) MCID Response (MCID <= -1.8 Points) Through Week 260 of Adalimumab Exposure(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260)
Number of Subjects Achieving the Patient Acceptable Symptoms State Through Week 260 of Adalimumab Exposure(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260)