Clinical trial NCT00939003: Study of Adalimumab in Patients With Axial Spondyloarthritis
Official title: A Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Axial Spondyloarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Axial Spondyloarthritis
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2009-07-14
Enrollment: 192
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: This study will evaluate how well adalimumab works in the short and long term in patients with axial spondyloarthritis who are not diagnosed as having either ankylosing spondylitis or psoriatic arthritis.

Detailed description: This is a Phase 3, placebo-controlled, double-blind randomized study with an open-label phase designed to evaluate the efficacy and safety of adalimumab 40 mg administered every other week in adult patients with active axial spondyloarthritis (SpA) who are not diagnosed with ankylosing spondylitis, psoriasis, or psoriatic arthritis and who have had an inadequate response or intolerance to one or more nonsteroidal anti-inflammatory drugs (NSAIDs) or had a contraindication to NSAIDs. Participants receive adalimumab or placebo for 12 weeks during the double-blind phase of the study. Following the double-blind phase, all remaining participants enter the open-label phase of the study in which they receive open-label adalimumab for up to 144 weeks. Efficacy endpoints include the Assessment of Spondyloarthritis International Society (ASAS) response criteria for patients with SpA. These response criteria were used to determine participants who were responders. ASAS response involves evaluations in the following 4 domains: participant's global assessment of disease activity, pain, function, and inflammation. The patient's global assessment of disease activity score is assessed using a 100 millimeter (mm) visual analog scale (VAS; 0 for no disease activity to 100 for severe disease activity). Pain is represented as a total back pain score and is assessed using a 100 mm VAS (0 for no pain to 100 for most severe pain). Function score is represented as the Bath Ankylosing Spondylitis (AS) Functional Index (BASFI) 100 mm VAS score (average of the ability to perform 10 activities, each scored as 0 for easy to 100 for impossible). Inflammation is determined using the morning stiffness overall level score (0 for none to 10 for very severe) and duration score (0 for 0 hours to 10 for ≥ 2 hours) of the Bath AS Disease Activity Index (BASDAI) (mean of these items #5 and #6 scores). In addition, the BASDAI is used as an efficacy endpoint. The BASDAI is used by the participant to assess his/her disease activity. Using VAS scales, the participant answers 6 questions pertaining to symptoms experienced over the past week. For 5 questions (levels of: fatigue/tiredness; AS neck, back, or hip pain; pain/swelling; discomfort at areas tender to touch or pressure; and morning stiffness), the response scale is 0 (none) to 10 (very severe). For 1 question (duration of morning stiffness), the response scale is 0 (0 hours) to 10 (≥ 2 or more hours).

Eligibility criteria: Inclusion Criteria:

* Adult patients with inadequate response to \>/= 1 non-steroidal anti-inflammatory drugs (NSAIDs)
* Chronic back pain with onset \< 45 years of age
* Magnetic resonance imaging (MRI) indicating active sacroiliitis or positive human leukocyte antigen-B27 (HLA-B27) blood test in addition to meeting spondyloarthritis clinical criteria
* Negative purified protein derivative (PPD) test and chest x-ray performed at Baseline visit must be negative
* Ability to administer subcutaneous injections
* General good health otherwise

Exclusion Criteria:

* Prior anti-tumor necrosis factor (TNF) therapy
* Psoriasis or psoriatic arthritis
* Fulfillment of modified New York criteria for ankylosing spondylitis
* Recent infection requiring treatment
* Significant medical events or conditions that may put patients at risk for participation
* Females who are pregnant or breast-feeding or considering becoming pregnant during the study
* History of cancer, except successfully treated skin cancer
* Recent history of drug or alcohol abuse

Primary outcomes:
measure: Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response
timeFrame: Baseline and Week 12
measure: Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response
timeFrame: Baseline and Week 12
measure: Change From Baseline in Short Form-36 (SF-36) Physical Component Summary Score
timeFrame: Baseline and Week 12
measure: Number of Participants Achieving ASAS Partial Remission
timeFrame: Week 12
measure: Number of Participants Achieving an ASAS5/6 Response
timeFrame: Baseline and Week 12
measure: Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S)
timeFrame: Baseline and Week 12
measure: Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)
timeFrame: Baseline and Week 12
measure: Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score for Sacroiliac Joints
timeFrame: Baseline and Week 12
measure: Change From Baseline in SPARCC MRI Score for the Spine
timeFrame: Baseline and Week 12
Other outcomes:
measure: Number of Participants Reporting Adverse Events
timeFrame: Through Week 12
measure: Number of Participants With Blood Hematology or Chemistry Values Common Toxicity Criteria Grade ≥ 3
timeFrame: Through Week 12
measure: Number of Participants Achieving an ASAS20 Response During the Open-label Period
timeFrame: Baseline and Weeks 52, 104, and 156
measure: Number of Participants Achieving an ASAS40 Response During the Open-label Period
timeFrame: Baseline and Weeks 52, 104, and 156
measure: Number of Participants Achieving a BASDAI50 Response During the Open-label Period
timeFrame: Baseline and Weeks 52, 104, and 156
Locations:
city: Birmingham
country: United States
facility: Site Reference ID/Investigator# 21250
state: Alabama
city: Colorado Springs
country: United States
facility: Site Reference ID/Investigator# 21249
state: Colorado
city: Denver
country: United States
facility: Site Reference ID/Investigator# 21245
state: Colorado
city: Wheaton
country: United States
facility: Site Reference ID/Investigator# 21246
state: Maryland
city: Duncansville
country: United States
facility: Site Reference ID/Investigator# 26582
state: Pennsylvania
city: Wyomissing
country: United States
facility: Site Reference ID/Investigator# 21241
state: Pennsylvania
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 21243
state: Texas
city: Houston
country: United States
facility: Site Reference ID/Investigator# 21248
state: Texas
city: Seattle
country: United States
facility: Site Reference ID/Investigator# 21247
state: Washington
city: Brisbane
country: Australia
facility: Site Reference ID/Investigator# 22342
city: Kogarah
country: Australia
facility: Site Reference ID/Investigator# 21223
city: Maroochydore
country: Australia
facility: Site Reference ID/Investigator# 21222
city: Genk
country: Belgium
facility: Site Reference ID/Investigator# 21225
city: Ghent
country: Belgium
facility: Site Reference ID/Investigator# 21224
city: Gilly
country: Belgium
facility: Site Reference ID/Investigator# 26544
city: Merksem
country: Belgium
facility: Site Reference ID/Investigator# 27382
city: Edmonton
country: Canada
facility: Site Reference ID/Investigator# 21229
city: Sainte-Foy, Quebec
country: Canada
facility: Site Reference ID/Investigator# 21226
city: St. John's
country: Canada
facility: Site Reference ID/Investigator# 21227
city: Toronto
country: Canada
facility: Site Reference ID/Investigator# 21228
city: Brno
country: Czech Republic
facility: Site Reference ID/Investigator# 21231
city: Pardubice
country: Czech Republic
facility: Site Reference ID/Investigator# 26882
city: Prague 2
country: Czech Republic
facility: Site Reference ID/Investigator# 21230
city: Uherske Hradiste
country: Czech Republic
facility: Site Reference ID/Investigator# 26883
city: Boulogne Billancourt
country: France
facility: Site Reference ID/Investigator# 21263
city: Chambray-les-Tour
country: France
facility: Site Reference ID/Investigator# 21262
city: Orleans
country: France
facility: Site Reference ID/Investigator# 21261
city: Paris Cedex 14
country: France
facility: Site Reference ID/Investigator# 22343
city: Berlin
country: Germany
facility: Site Reference ID/Investigator# 21266
city: Erlangen
country: Germany
facility: Site Reference ID/Investigator# 21267
city: Herne
country: Germany
facility: Site Reference ID/Investigator# 21264
city: Munich
country: Germany
facility: Site Reference ID/Investigator# 21265
city: Amsterdam
country: Netherlands
facility: Site Reference ID/Investigator# 21285
city: Leiden
country: Netherlands
facility: Site Reference ID/Investigator# 21284
city: A Coruna
country: Spain
facility: Site Reference ID/Investigator# 21282
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 21283
city: Cordoba
country: Spain
facility: Site Reference ID/Investigator# 21281
city: Newcastle upon Tyne
country: United Kingdom
facility: Site Reference ID/Investigator# 21289
Study officials:
affiliation: AbbVie
name: Aileen L Pangan, MD
role: STUDY_DIRECTOR
References:
citation: van der Heijde D, Sieper J, Maksymowych WP, Lambert RG, Chen S, Hojnik M, Anderson JK, Pangan AL. Clinical and MRI remission in patients with nonradiographic axial spondyloarthritis who received long-term open-label adalimumab treatment: 3-year results of the ABILITY-1 trial. Arthritis Res Ther. 2018 Mar 27;20(1):61. doi: 10.1186/s13075-018-1556-5.
citation: van der Heijde D, Sieper J, Maksymowych WP, Brown MA, Lambert RG, Rathmann SS, Pangan AL. Spinal inflammation in the absence of sacroiliac joint inflammation on magnetic resonance imaging in patients with active nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2014 Mar;66(3):667-73. doi: 10.1002/art.38283.
citation: Sieper J, van der Heijde D, Dougados M, Mease PJ, Maksymowych WP, Brown MA, Arora V, Pangan AL. Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: results of a randomised placebo-controlled trial (ABILITY-1). Ann Rheum Dis. 2013 Jun;72(6):815-22. doi: 10.1136/annrheumdis-2012-201766. Epub 2012 Jul 7.