A Multicentre, 12 Week Double Blind Placebo Controlled Randomized Study Of Etanercept On A Background Nsaid In The Treatment Of Adult Subjects With Non Radiographic Axial Spondyloarthritis With A 92 Week Open Label Extension
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Pfizer
- Enrollment
- 225
- Locations
- 50
- Primary Endpoint
- Percentage of Participants Achieving Ankylosing Spondylitis (ASAS) 40 Response at Week 12
Study Overview
Brief Summary
This is a two part study. During period one there will be a comparison of Etanercept (ETN) against a placebo with both arms maintaining the background anti inflammatory drug prescribed by their Physician. The hypothesis is that Etanercept will be superior to the placebo arm as determined by the proportion of subjects achieving Assessments in Ankylosing Spondylitis (ASAS)40 improvement at 12 weeks. This will be followed by 92 weeks extension where everyone in the trial receives Etanercept (ETN) and a background non steroidal anti inflammatory drug(NSAID).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 49 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of axial spondyloarthritis as defined by Assessments in Ankylosing Spondylitis (ASAS)criteria
- •Active symptoms defined as Ankylosing Spondylitis Disease Activity Index{BASDAI) > or = 4
- •Axial symptoms of back pain with a less than favorable response to on steroidal anti inflammatory drugs at optimal dosage for greater than 4 weeks
Exclusion Criteria
- •Evidence of current or recent episode of uveitis
- •Evidence of IBD flare within 6 months
- •Previous treatment with an anti Tumor necrosis factor(TNF)
- •Active tuberculosis
- •Radiographic sacroiliitis grade 3-4 unilaterally or >= 2 bilaterally
Arms & Interventions
etanercept
In Period 1 : Subjects will receive via a prefilled syringe an active dose equivalent to 1.0ml of Etanercept solution once weekly SC once weekly. Additionally they will continue to take the background non steroidal anti inflammatory drug(NSAID) in the tolerated dose agreed upon by the attending Physician.
Intervention: etanercept (Biological)
etanercept
In Period 1 : Subjects will receive via a prefilled syringe an active dose equivalent to 1.0ml of Etanercept solution once weekly SC once weekly. Additionally they will continue to take the background non steroidal anti inflammatory drug(NSAID) in the tolerated dose agreed upon by the attending Physician.
Intervention: Background NSAID (Drug)
PLACEBO
In Period 1: Subjects will receive in a prefilled syringe with a PLACEBO dose equivalent to 1.0 ml of placebo solution once weekly SC Additionally they will continue to take the background non steroidal anti inflammatory drug(NSAID) in the tolerated dose agreed upon by the attending Physician.
Intervention: PLACEBO (Other)
PLACEBO
In Period 1: Subjects will receive in a prefilled syringe with a PLACEBO dose equivalent to 1.0 ml of placebo solution once weekly SC Additionally they will continue to take the background non steroidal anti inflammatory drug(NSAID) in the tolerated dose agreed upon by the attending Physician.
Intervention: Background NSAID (Drug)
Outcomes
Primary Outcomes
Percentage of Participants Achieving Ankylosing Spondylitis (ASAS) 40 Response at Week 12
Time Frame: Week 12
ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) in 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 40 = 40% improvement from baseline and an absolute change ≥ 20 units on a 0-100 scale (0 = no disease activity, 100 = high disease activity) for ≥ 3 domains, and no worsening in remaining domain.
Secondary Outcomes
- Percentage of Participants Achieving ASAS 40 Response at Time Points(Baseline to Week 104)
- Percentage of Participants Achieving ASAS Partial Remission at Time Points(Baseline to Week 104)
- Mean Change From Baseline in Visual Analogue Scale (VAS) Physician Global Assessments at Time Points(Baseline to Week 104)
- Mean Change From Baseline in VAS Score for Subject Assessment of Disease Activity at Time Points(Baseline to Week 104)
- Time to ASAS Partial Remission(Week 12)
- Percentage of Participants Achieving ASAS 20 Response at Time Points(Baseline to Week 104)
- Percentage of Participants Achieving ASAS 5/6 Response at Time Points(Baseline to Week 104)
- Changes From Baseline in VAS Score for Total Back Pain at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASFI Standing Unsupported for 10 Minutes at Time Points(Baseline to Week 104)
- Changes From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Total Score at Time Points(Baseline to Week 104)
- Mean Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) High Sensitivity CRP (hsCRP) Score at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASFI Full Day Activities at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASFI Bending Forward at Time Points(Baseline to Week 104)
- Changes From Baseline in VAS Score for Nocturnal Back Pain at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASFI Getting-up Off-floor From Back at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASFI Looking Over Shoulder at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASDAI Level of How Long Stiffness Lasts at Time Points(Baseline to Week 104)
- Percentage of Participants With BASDAI 20 at Time Points(Baseline to Week 104)
- Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) - Spine 6 Discovertebral Units (DVU) Total Score at 12 Weeks(Week 12)
- Mean Change From Baseline in Number of Swollen Joints at Time Points(Baseline to Week 104)
- Changes From Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) Total Score at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASFI Reaching up High at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASFI Climbing Steps Without Aid at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASFI Getting Out of an Arm-less Chair at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASFI Physically Demanding Activities at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASFI Putting on Socks at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASDAI Level of Discomfort at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASDAI Level of Pain/Swelling at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASDAI Level of Morning Stiffness at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASDAI Level of Fatigue/Tiredness at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASDAI Level of Neck/Back/Hip Pain at Time Points(Baseline to Week 104)
- Percentage of Participants With BASDAI 50 at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASMI Lateral Side Flexion Score by Time Point(Baseline to Week 104)
- Change From Baseline in Bath Ankylosing Spondylitis Global Index (BAS-G) Total Score at Time Points(Baseline to Week 104)
- Change From Baseline in Chest Expansion at Time Points(Baseline to Week 104)
- Mean Change From Baseline in BASMI Cervical Rotation Degree by Time Point(Baseline to Week 104)
- Mean Change From Baseline in BASMI Modified Schobers Test Score by Time Point(Baseline to Week 104)
- Mean Change From Baseline in BASMI Intermalleolar Distance Score by Time Point(Baseline to Week 104)
- Mean Change From Baseline in BASMI Tragus to Wall Score by Time Point(Baseline to Week 104)
- Mean Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Total Score at Time Points(Baseline to Week 104)
- Mean Change From Baseline in SPARCC - Spine 6 Discovertebral Units (DVU) Total Score at Time Points(Weeks 12 and 104)
- Mean Change From Baseline in Dactylitis Score at Time Points(Baseline to Week 104)
- Change From Baseline in HADS Anxiety Score at Time Points(Baseline to Week 104)
- Mean Change From Baseline in SPARCC Score for the Sacroiliac Joint at Time Points(Weeks 12 and 104)
- Mean Change From Baseline in Ankylosing Spondylitis Spine Magnetic Resonance Imaging-Activity (ASspiMRI-a) Total Score(Weeks 12 and 104)
- Changes From Baseline in Maastricht Ankylosing Spondylitis Enthesis Score (MASES) at Time Points(Baseline to Week 104)
- Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Depression Score at Time Points(Baseline to Week 104)
- Change From Baseline in WPAI: Percent Impairment While Working Due to Health Problems at Time Points(Baseline to Week 104)
- Mean Change From Baseline in Occiput-to-wall Test at Time Points(Baseline to Week 104)
- Mean Change From Baseline in Number of Tender Joints at Time Points(Baseline to Week 104)
- Change From Baseline in C-reactive Protein (CRP) Concentration Time Points(Baseline to Week 104)
- Change From Baseline in Short Form-36 (SF-36) Physical Component Summary (PCS) at Time Points(Baseline to Week 104)
- Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Time Points(Baseline to Week 104)
- Change From Baseline in Euro Quality of Life (EQ)-5D VAS Score Time Points(Baseline to Week 104)
- Change From Baseline in SF-36 Mental Component Summary (MCS) at Time Points(Baseline to Week 104)
- Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score at Time Points(Baseline to Week 104)
- Change From Baseline in Ankylosing Spondylitis Work Instability Index (AS-WIS) Score at Time Points(Baseline to Week 104)
- Percentage of Participants With Minimally Clinically Important Improvement (MCII) at Time Points(Weeks 12 and 104)
- Percentage of Participants Achieving Patient Acceptable Symptom State (PASS) at Time Points(Weeks 12 and 104)
- Change From Baseline in EQ-5D Health State Profile Utility Score at Time Points(Baseline to Week 104)
- Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Due to Health Problems at Time Points(Baseline to Week 104)
- Changes From Baseline in WPAI - Overall Work Impairment Due to Health Problems at Time Points(Baseline to Week 104)
- Change From Baseline in Multidimensional Fatigue Inventory (MFI) Score at Time Points(Baseline to Week 104)
- Changes From Baseline in WPAI - Activity Impairment Due to Health Problems at Time Points(Baseline to Week 104)
- Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Score From Baseline to Week 104(Baseline to Week 104)