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

Abbott9 sites in 1 country82 target enrollmentDecember 2003

ConditionsAnkylosing Spondylitis

Overview

Phase: Phase 3
Intervention: Not specified
Conditions: Ankylosing Spondylitis
Sponsor: Abbott
Enrollment: 82
Locations: 9
Primary Endpoint: Number of Subjects With a Reduction in Signs and Symptoms as Measured by Assessments of Ankylosing Spondylitis (ASAS) 20 Response at Week 12
Status: Completed
Last Updated: 14 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

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

Registry

clinicaltrials.gov

Start Date

December 2003

End Date

June 2009

Last Updated

14 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Abbott

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

Outcomes

Primary Outcomes

Number of Subjects With a Reduction in Signs and Symptoms as Measured by Assessments of Ankylosing Spondylitis (ASAS) 20 Response at Week 12

Time Frame: Week 12

ASAS 20 responders - improvement of \>=20% and absolute improvement of \>=10 units from Baseline in a visual analog scale (VAS) 0 \[no disease activity\]-100 \[high disease activity\]) 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 \[severe\]), BAth Ankylosing Spondylitis Functional Index (BASFI) VAS (0 \[easy \]-100\[impossible\]); and Inflammation VAS; (1 \[no pain\] to 10 \[severe pain\]) and absence of deterioration in the potential remaining domain. 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: Baseline and 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 by Assessments in Ankylosing Spondylitis (ASAS) 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) 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(Weeks 12, 24, 36, 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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Total Back Pain (an Individual Component of ASAS 20) Through Week 260 of Adalimumab Exposure(Weeks 12, 24, 52, 76, 128, 152, 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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(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(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, 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)
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(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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in Edmonton Ankylosing Spondylitis Metrology Index (EDASMI) in Subjects With Adalimumab Exposure Through Week 260(Weeks 12, 24, 52, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in Chest Expansion (CE) in Subjects With Adalimumab Exposure Through Week 260(Weeks 12, 24, 52,104, 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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260)
Mean Change in the Bath Ankylosing Spondylitis Global Index (BAS-G) 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 Swollen Joint Count for 44 Joints (44 SJC) in Subjects With Adalimumab Exposure Through Week 260(Weeks 12, 24, 36, 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 of Adalimumab Exposure(Weeks 12, 24, 36, 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(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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
Mean Change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale in Subjects With Adalimumab Exposure Through Week 260(Baseline and at Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260)
Mean Change in the SF-36 Health Survey Index Physical Component Summary [PCS] Through Week 260 of Adalimumab Exposure(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(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(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(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 and at 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)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260)
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(Week 12 and Week 52)
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(Weeks 12 and 52)