Clinical trial NCT01258738: Study Comparing Etanercept (ETN) Against a Placebo for Etanercept on a Background Nonsteroidal Anti Inflammatory Drug (NSAIDs) in the Treatment of Early Spondyloarthritis (SpA) Patients Who do Not Have X-ray Structural Changes
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Spondylitis, Ankylosing
Keywords: Early ankylosing spondylitis (SpA) study; efficacy and safety and health out comes
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-12-13
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Achieving Ankylosing Spondylitis (ASAS) 40 Response at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of Participants Achieving ASAS 40 Response at Time Points
timeFrame: Baseline to Week 104
measure: Percentage of Participants Achieving ASAS 20 Response at Time Points
timeFrame: Baseline to Week 104
measure: Percentage of Participants Achieving ASAS 5/6 Response at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) High Sensitivity CRP (hsCRP) Score at Time Points
timeFrame: Baseline to Week 104
measure: Percentage of Participants Achieving ASAS Partial Remission at Time Points
timeFrame: Baseline to Week 104
measure: Time to ASAS Partial Remission
timeFrame: Week 12
measure: Mean Change From Baseline in Visual Analogue Scale (VAS) Physician Global Assessments at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in VAS Score for Subject Assessment of Disease Activity at Time Points
timeFrame: Baseline to Week 104
measure: Changes From Baseline in VAS Score for Nocturnal Back Pain at Time Points
timeFrame: Baseline to Week 104
measure: Changes From Baseline in VAS Score for Total Back Pain at Time Points
timeFrame: Baseline to Week 104
measure: Changes From Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) Total Score at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASFI Full Day Activities at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASFI Bending Forward at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASFI Getting Out of an Arm-less Chair at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASFI Physically Demanding Activities at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASFI Reaching up High at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASFI Climbing Steps Without Aid at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASFI Getting-up Off-floor From Back at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASFI Standing Unsupported for 10 Minutes at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASFI Looking Over Shoulder at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASFI Putting on Socks at Time Points
timeFrame: Baseline to Week 104
measure: Changes From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Total Score at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASDAI Level of Morning Stiffness at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASDAI Level of Fatigue/Tiredness at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASDAI Level of Discomfort at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASDAI Level of How Long Stiffness Lasts at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASDAI Level of Pain/Swelling at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASDAI Level of Neck/Back/Hip Pain at Time Points
timeFrame: Baseline to Week 104
measure: Percentage of Participants With BASDAI 50 at Time Points
timeFrame: Baseline to Week 104
measure: Percentage of Participants With BASDAI 20 at Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in Bath Ankylosing Spondylitis Global Index (BAS-G) Total Score at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Total Score at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASMI Lateral Side Flexion Score by Time Point
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASMI Cervical Rotation Degree by Time Point
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASMI Modified Schobers Test Score by Time Point
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASMI Intermalleolar Distance Score by Time Point
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in BASMI Tragus to Wall Score by Time Point
timeFrame: Baseline to Week 104
measure: Change From Baseline in Chest Expansion at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in Occiput-to-wall Test at Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) - Spine 6 Discovertebral Units (DVU) Total Score at 12 Weeks
timeFrame: Week 12
measure: Mean Change From Baseline in SPARCC Score for the Sacroiliac Joint at Time Points
timeFrame: Weeks 12 and 104
measure: Mean Change From Baseline in SPARCC - Spine 6 Discovertebral Units (DVU) Total Score at Time Points
timeFrame: Weeks 12 and 104
measure: Mean Change From Baseline in Ankylosing Spondylitis Spine Magnetic Resonance Imaging-Activity (ASspiMRI-a) Total Score
timeFrame: Weeks 12 and 104
measure: Mean Change From Baseline in Number of Swollen Joints at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in Number of Tender Joints at Time Points
timeFrame: Baseline to Week 104
measure: Mean Change From Baseline in Dactylitis Score at Time Points
timeFrame: Baseline to Week 104
measure: Changes From Baseline in Maastricht Ankylosing Spondylitis Enthesis Score (MASES) at Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in C-reactive Protein (CRP) Concentration Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in Euro Quality of Life (EQ)-5D VAS Score Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in EQ-5D Health State Profile Utility Score at Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in Short Form-36 (SF-36) Physical Component Summary (PCS) at Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in SF-36 Mental Component Summary (MCS) at Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Depression Score at Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in HADS Anxiety Score at Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score at Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in Ankylosing Spondylitis Work Instability Index (AS-WIS) Score at Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Due to Health Problems at Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in WPAI: Percent Impairment While Working Due to Health Problems at Time Points
timeFrame: Baseline to Week 104
measure: Changes From Baseline in WPAI - Activity Impairment Due to Health Problems at Time Points
timeFrame: Baseline to Week 104
measure: Changes From Baseline in WPAI - Overall Work Impairment Due to Health Problems at Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in Multidimensional Fatigue Inventory (MFI) Score at Time Points
timeFrame: Baseline to Week 104
measure: Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Score From Baseline to Week 104
timeFrame: Baseline to Week 104
measure: Percentage of Participants With Minimally Clinically Important Improvement (MCII) at Time Points
timeFrame: Weeks 12 and 104
measure: Percentage of Participants Achieving Patient Acceptable Symptom State (PASS) at Time Points
timeFrame: Weeks 12 and 104
Other outcomes:
Locations:
city: San Miguel de Tucuman
country: Argentina
facility: Centro Medico Privado de Reumatologia
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Consultorios Reumatológicos Pampa
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Hasselt
country: Belgium
facility: Reuma Instituut
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Chia
country: Colombia
facility: Preventive Care Ltda.
state: Cundinamarca
city: Bucaramanga
country: Colombia
facility: Ips Medicity S.A.S
state: Santander
city: Bucaramanga
country: Colombia
facility: Servimed Sas
state: Santander
city: Praha 11 - Chodov
country: Czech Republic
facility: Mediscan Group, s.r.o.
city: Praha 2
country: Czech Republic
facility: Revmatologicky ustav
city: Uherske Hradiste
country: Czech Republic
facility: Medical Plus s.r.o.
city: Helsinki
country: Finland
facility: Meilahden kolmiosairaala
city: Hyvinkää
country: Finland
facility: Kiljavan Lääketutkimus
city: LE KREMLIN-BICETRE Cedex
country: France
facility: Hopital de Bicetre
city: Montpellier
country: France
facility: CHU Lapeyronie, Immuno-Rhumatologie
city: Paris
country: France
facility: Hôpital Cochin
city: Tours Cedex 9
country: France
facility: CHU de Tours
city: Berlin
country: Germany
facility: Charite - Campus Benjamin Franklin, Medizinische Klinik I - Rheumatologie
city: Erlangen
country: Germany
facility: Studienambulanz, Medizinische Klinik 3, Universitaetsklinikum Erlangen
city: Hamburg
country: Germany
facility: Schoen Klinik Hamburg-Eilbek, Abt. Rheumatologie und Klin. Immunologie
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet
city: Vogelsang-Gommern
country: Germany
facility: MEDIGREIF Verwaltungs- und Betriebsgesellschaft Fachkrankenhaus Vogelsang-Gommern mbH
city: Budapest
country: Hungary
facility: Orszagos Reumatologiai es Fizioterapias Intezet/Klinikai Immunologiai es Reumatologiai Osztaly
city: Budapest
country: Hungary
facility: Budai Irgalmasrendi Korhaz
city: Budapest
country: Hungary
facility: Qualiclinic Egeszsegugyi Szolgaltato es Kutatasszervezo Kft.
city: Budapest
country: Hungary
facility: Synexus Magyarorszag Egeszsegugyi Szolgaltato Kft.
city: Debrecen
country: Hungary
facility: Kenezy Gyula Korhaz es Rendelointezet
city: Veszprem
country: Hungary
facility: Csolnoky Ferenc Korhaz
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Hospital
state: Gwangyeogsiv
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Hospital
city: Amsterdam
country: Netherlands
facility: Academic Medical Centre (AMC) / Division of Clinical Immunology and Rheumatology
state: North-Holland
city: Leiden
country: Netherlands
facility: Leiden University Medical Center, Reumatologie
city: Moscow
country: Russian Federation
facility: Rheumatology Research Institute of Russian Academy of Medical Sciences
city: Moscow
country: Russian Federation
facility: Russian Cardiology Research-and-Production Complex
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg State Budgetary Healthcare Institution
city: Saint-Petersburg
country: Russian Federation
facility: Limited Liability Company NMC Tomography
city: Saint-Petersburg
country: Russian Federation
facility: Leningrad Regional Clinical Hospital
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
state: Andalucia
city: Alcorcon
country: Spain
facility: Fundacion Hospital Alcorcon
state: Madrid
city: Cordoba
country: Spain
facility: Hospital Reina Sofia
city: La Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
city: Kaohsiung
country: Taiwan
facility: Chung-Ho Memorial Hospital, Kaohsiung Medical University
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Cambridge
country: United Kingdom
facility: Rhuematology Clinical Research Unit
state: Cambridgeshire
city: Basingstoke
country: United Kingdom
facility: Hampshire Hospitals NHS Foundation Trust
state: Hants.
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital NHS Trust
state: Norfolk
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
state: West Midlands
city: London
country: United Kingdom
facility: Whipps Cross University Hospital,
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Schneeberger EE, Citera G, de Leon DP, Szumski AE, Kwok K, Cutri M, Dougados M. Simplified Ankylosing Spondylitis Disease Activity Score (SASDAS) Versus ASDAS: A Post Hoc Analysis of a Randomized Controlled Trial. J Rheumatol. 2022 Oct;49(10):1100-1108. doi: 10.3899/jrheum.211075. Epub 2022 Jul 15.
citation: Maksymowych WP, Claudepierre P, de Hooge M, Lambert RG, Landewe R, Molto A, van der Heijde D, Bukowski JF, Jones H, Pedersen R, Szumski A, Vlahos B, Dougados M. Structural changes in the sacroiliac joint on MRI and relationship to ASDAS inactive disease in axial spondyloarthritis: a 2-year study comparing treatment with etanercept in EMBARK to a contemporary control cohort in DESIR. Arthritis Res Ther. 2021 Jan 29;23(1):43. doi: 10.1186/s13075-021-02428-8.
citation: Dougados M, van der Heijde D, Tsai WC, Saaibi D, Marshall L, Jones H, Pedersen R, Vlahos B, Tarallo M. Relationship between disease activity status or clinical response and patient-reported outcomes in patients with non-radiographic axial spondyloarthritis: 104-week results from the randomized controlled EMBARK study. Health Qual Life Outcomes. 2020 Jan 3;18(1):4. doi: 10.1186/s12955-019-1260-4.
citation: Dougados M, Maksymowych WP, Landewe RBM, Molto A, Claudepierre P, de Hooge M, Lambert RG, Bonin R, Bukowski JF, Jones HE, Logeart I, Pedersen R, Szumski A, Vlahos B, van der Heijde D. Evaluation of the change in structural radiographic sacroiliac joint damage after 2 years of etanercept therapy (EMBARK trial) in comparison to a contemporary control cohort (DESIR cohort) in recent onset axial spondyloarthritis. Ann Rheum Dis. 2018 Feb;77(2):221-227. doi: 10.1136/annrheumdis-2017-212008. Epub 2017 Sep 29.
citation: Maksymowych WP, Wichuk S, Dougados M, Jones HE, Pedersen R, Szumski A, Marshall L, Bukowski JF, Lambert RG. Modification of structural lesions on MRI of the sacroiliac joints by etanercept in the EMBARK trial: a 12-week randomised placebo-controlled trial in patients with non-radiographic axial spondyloarthritis. Ann Rheum Dis. 2018 Jan;77(1):78-84. doi: 10.1136/annrheumdis-2017-211605. Epub 2017 Sep 29.
citation: Brown MA, Bird PA, Robinson PC, Mease PJ, Bosch FVD, Surian C, Jones H, Szumski A, Marshall L, Wiid Z, Dougados M. Evaluation of the effect of baseline MRI sacroiliitis and C reactive protein status on etanercept treatment response in non-radiographic axial spondyloarthritis: a post hoc analysis of the EMBARK study. Ann Rheum Dis. 2018 Jul;77(7):1091-1093. doi: 10.1136/annrheumdis-2017-211313. Epub 2017 Jul 3. No abstract available.
citation: Maksymowych WP, Wichuk S, Dougados M, Jones H, Szumski A, Bukowski JF, Marshall L, Lambert RG. MRI evidence of structural changes in the sacroiliac joints of patients with non-radiographic axial spondyloarthritis even in the absence of MRI inflammation. Arthritis Res Ther. 2017 Jun 6;19(1):126. doi: 10.1186/s13075-017-1342-9.
citation: Dougados M, van der Heijde D, Sieper J, Braun J, Citera G, Lenaerts J, van den Bosch F, Wei JC, Pedersen R, Bonin R, Jones H, Marshall L, Logeart I, Vlahos B, Bukowski JF, Maksymowych WP. Effects of Long-Term Etanercept Treatment on Clinical Outcomes and Objective Signs of Inflammation in Early Nonradiographic Axial Spondyloarthritis: 104-Week Results From a Randomized, Placebo-Controlled Study. Arthritis Care Res (Hoboken). 2017 Oct;69(10):1590-1598. doi: 10.1002/acr.23276. Epub 2017 Aug 31.
citation: Maksymowych WP, Dougados M, van der Heijde D, Sieper J, Braun J, Citera G, Van den Bosch F, Logeart I, Wajdula J, Jones H, Marshall L, Bonin R, Pedersen R, Vlahos B, Kotak S, Bukowski JF. Clinical and MRI responses to etanercept in early non-radiographic axial spondyloarthritis: 48-week results from the EMBARK study. Ann Rheum Dis. 2016 Jul;75(7):1328-35. doi: 10.1136/annrheumdis-2015-207596. Epub 2015 Aug 12.
citation: Dougados M, van der Heijde D, Sieper J, Braun J, Maksymowych WP, Citera G, Miceli-Richard C, Wei JC, Pedersen R, Bonin R, Rahman MU, Logeart I, Wajdula J, Koenig AS, Vlahos B, Alvarez D, Bukowski JF. Symptomatic efficacy of etanercept and its effects on objective signs of inflammation in early nonradiographic axial spondyloarthritis: a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 2014 Aug;66(8):2091-102. doi: 10.1002/art.38721.