Clinical trial NCT03178487: A Study Evaluating the Safety and Efficacy of Upadacitinib in Adults With Active Ankylosing Spondylitis
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ankylosing Spondylitis (AS)
Keywords: Upadacitinib
ABT-494
Ankylosing Spondylitis (AS)
Safety
Efficacy
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2017-06-07
Enrollment: 187
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: The purpose of this study is to evaluate the safety and efficacy of upadacitinib in participants with active ankylosing spondylitis (AS) who have had an inadequate response to at least 2 non-steroidal anti-inflammatory drugs (NSAIDs) or intolerance to or a contraindication for NSAIDs, and who are naïve to biologic disease-modifying anti-rheumatic drugs (bDMARD).

Detailed description: This study includes two periods: a 14-week double-blind placebo-controlled period and a 90-week open-label long-term extension period.

Eligible participants were randomly assigned in a 1:1 ratio to receive upadacitinib 15 mg or placebo for 14 weeks in Period 1.

Participants who completed Period 1 received upadacitinib 15 mg for 90 weeks in the extension period.

Eligibility criteria: Inclusion Criteria:

* Participant with a clinical diagnosis of ankylosing spondylitis (AS) and meeting the modified New York criteria for AS.
* Participant must have baseline disease activity as defined by having a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score \>= 4 and a Patient's Assessment of Total Back Pain score \>= 4 based on a 0 - 10 numeric rating scale (NRS) at the Screening and Baseline visits.
* Participant has had an inadequate response to at least two nonsteroidal anti-inflammatory drugs (NSAIDs) over an at least 4-week period in total at maximum recommended or tolerated doses, or participant has an intolerance to or contraindication for NSAIDs as defined by the Investigator.
* If entering the study on concomitant methotrexate (MTX), leflunomide, sulfasalazine (SSZ), and/or hydroxychloroquine, participant must be on a stable dose of MTX (\<= 25 mg/week) and/or SSZ (\<= 3 g/day) and/or hydroxychloroquine (\<= 400 mg/day) or leflunomide (\<= 20 mg/day) for at least 28 days prior to the Baseline visit. A combination of up to two background conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) is allowed except the combination of MTX and leflunomide.
* If entering the study on concomitant oral corticosteroids, participant must be on a stable dose of prednisone (\<= 10 mg/day), or oral corticosteroid equivalents, for at least 14 days prior to the Baseline visit.
* If entering the study on concomitant NSAIDs, tramadol, combination of acetaminophen and codeine or hydrocodone, and/or non-opioid analgesics, participant must be on stable dose(s) for at least 14 days prior to the Baseline visit.

Exclusion Criteria:

* Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
* Prior exposure to any biologic therapy with a potential therapeutic impact on spondyloarthritis (SpA).
* Intra-articular joint injections, spinal/paraspinal injection(s), or parenteral administration of corticosteroids within 28 days prior to the Baseline visit. Inhaled or topical corticosteroids are allowed.
* Participant on any other DMARDs (other than those allowed), thalidomide or apremilast within 28 days or five half-lives (whichever is longer) of the drug prior to the Baseline visit.
* Participant on opioid analgesics (except for combination acetaminophen/codeine or acetaminophen/hydrocodone which are allowed) or use of inhaled marijuana within 14 days prior to the Baseline visit.
* Participant has a history of inflammatory arthritis of different etiology other than axial SpA (including but not limited to rheumatoid arthritis, psoriatic arthritis, mixed connective tissue disease, systemic lupus erythematosus, reactive arthritis, scleroderma, polymyositis, dermatomyositis, fibromyalgia), or any arthritis with onset prior to 17 years of age.
* Laboratory values meeting the following criteria within the Screening period prior to the first dose of study drug: serum aspartate transaminase \> 2 × upper limit of normal (ULN); serum alanine transaminase \> 2 × ULN; estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease formula \< 40 milliliter (mL)/minute/1.73m\^2; hemoglobin \< 10 gram/deciliter, total white blood cell count \< 2,500/microliter (μL); absolute neutrophil count \< 1,500/μL; absolute lymphocyte count \< 800/μL; and platelet count \< 100,000/μL.

Primary outcomes:
measure: Percentage of Participants With Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 14
timeFrame: Baseline and Week 14
Secondary outcomes:
measure: Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 14
timeFrame: Baseline and Week 14
measure: Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score for the Spine at Week 14
timeFrame: Baseline and Week 14
measure: Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Week 14
timeFrame: Baseline and Week 14
measure: Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score
timeFrame: Baseline and Week 14
measure: Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) Partial Remission
timeFrame: Week 14
measure: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 14
timeFrame: Baseline and Week 14
measure: Change From Baseline in Linear Bath Ankylosing Spondylitis Metrology Index (BASMI[Lin]) at Week 14
timeFrame: Baseline and Week 14
measure: Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Week 14
timeFrame: Baseline and Week 14
measure: Change From Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment at Week 14
timeFrame: Baseline and Week 14
measure: Change From Baseline in ASAS Health Index (HI) at Week 14
timeFrame: Baseline and Week 14
measure: Percentage of Participants Achieving an ASAS 20 Response at Week 14
timeFrame: Baseline and Week 14
measure: Change From Baseline in SPARCC MRI Score for Sacroiliac Joints at Week 14
timeFrame: Baseline and Week 14
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Arthritis & Rheumatolo /ID# 164446
state: Arizona
city: Phoenix
country: United States
facility: AZ Arthritis and Rheumotology Research, PLLC /ID# 165705
state: Arizona
city: Beverly Hills
country: United States
facility: David S. Hallegua MD /ID# 165090
state: California
city: Covina
country: United States
facility: Covina Arthritis Clinic /ID# 165061
state: California
city: Fullerton
country: United States
facility: St. Joseph Health System /ID# 166166
state: California
city: Los Angeles
country: United States
facility: Global Research Foundation /ID# 165130
state: California
city: San Diego
country: United States
facility: Rheumatology Center of San Diego /ID# 166167
state: California
city: Lakewood
country: United States
facility: Colorado Arthritis Associates /ID# 164444
state: Colorado
city: Brandon
country: United States
facility: Bay Area Arthritis and Osteo /ID# 165023
state: Florida
city: Miami
country: United States
facility: LeJenue Research Associates /ID# 165202
state: Florida
city: Orlando
country: United States
facility: HMD Research LLC /ID# 205172
state: Florida
city: Meridian
country: United States
facility: St. Lukes Clinic /ID# 165827
state: Idaho
city: Skokie
country: United States
facility: Clinical Investigation Specialists - Skokie /ID# 164385
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Health System /ID# 165515
state: Michigan
city: Grand Blanc
country: United States
facility: Aa Mrc Llc /Id# 165100
state: Michigan
city: Potsdam
country: United States
facility: St. Lawrence Health System /ID# 165025
state: New York
city: Charlotte
country: United States
facility: DJL Clinical Research, PLLC /ID# 165044
state: North Carolina
city: Duncansville
country: United States
facility: Altoona Ctr Clinical Res /ID# 164470
state: Pennsylvania
city: Wyomissing
country: United States
facility: Clinical Research Ctr Reading /ID# 164876
state: Pennsylvania
city: Hendersonville
country: United States
facility: Comprehensive Arthritis Care, a division of Comprehensive Rheumatology Care PLLC /ID# 168107
state: Tennessee
city: Beaumont
country: United States
facility: Diagnostic Group Integrated He /ID# 165195
state: Texas
city: College Station
country: United States
facility: Arth and Osteo Clin Brazo Valley /ID# 165194
state: Texas
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital /ID# 169239
state: Queensland
city: Camberwell
country: Australia
facility: Emeritus Research /ID# 169240
state: Victoria
city: Gent
country: Belgium
facility: UZ Gent /ID# 166017
state: Oost-Vlaanderen
city: Genk
country: Belgium
facility: ReumaClinic Genk /ID# 166018
city: Leuven
country: Belgium
facility: UZ Leuven /ID# 166019
city: Edmonton
country: Canada
facility: Rheumatology Research Assoc /ID# 165240
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta - Division of Rheumatology /ID# 165239
state: Alberta
city: Mississauga
country: Canada
facility: Credit Valley Rheumatology /ID# 200087
state: Ontario
city: Sainte-foy
country: Canada
facility: Groupe de Recherche en Maladies Osseuses Inc /ID# 165238
state: Quebec
city: Zagreb
country: Croatia
facility: Clinical Hospital Dubrava /ID# 167049
city: Zagreb
country: Croatia
facility: Medical Center Kuna-Peric /ID# 164851
city: Prague 2
country: Czechia
facility: Revmatologicky ustav Praha /ID# 167004
state: Praha 2
city: Prague 4
country: Czechia
facility: Thomayerova nemocnice /ID# 167003
state: Praha 4
city: Brno
country: Czechia
facility: REVMACLINIC s.r.o. /ID# 167171
city: Pardubice
country: Czechia
facility: ARTHROHELP, s.r.o. /ID# 167001
city: Vejle
country: Denmark
facility: Vejle Sygehus /ID# 165190
state: Syddanmark
city: Helsinki
country: Finland
facility: Helsinki Univ Central Hospital /ID# 165794
city: Hyvinkaa
country: Finland
facility: Kiljava Medical Research /ID# 165793
city: Bordeaux
country: France
facility: CHU Bordeaux-Hopital Pellegrin /ID# 166309
city: Chambray Les Tours
country: France
facility: CHRU Tours - Hopital Trousseau /ID# 165109
city: Montpellier
country: France
facility: CHRU de Montpellier - Hôpital Lapeyronie /ID# 166308
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet /ID# 165148
state: Nordrhein-Westfalen
city: Bad Nauheim
country: Germany
facility: Kerckhoff Klinik GmbH /ID# 165158
city: Berlin
country: Germany
facility: Charite - Campus Benjamin Franklin Medizinische Klinik - Rheumatologie /ID# 165153
city: Hamburg
country: Germany
facility: Hamburger Rheuma Forschungszentrum II im MVZ Rheumatologie und Autoimmunmedizin /ID# 165146
city: Budapest
country: Hungary
facility: Revita Reumatologiai Rendelo /ID# 164724
city: Debrecen
country: Hungary
facility: University of Debrecen /ID# 165674
city: Szekesfehervar
country: Hungary
facility: Vita Verum Medical Bt. /ID# 165066
city: Veszprem
country: Hungary
facility: Vital Medical Center Orvosi-es Fogaszati Kozpont /ID# 164741
city: Bologna
country: Italy
facility: Ospedale Sant Orsola Malpighi /ID# 165692
state: Emilia-Romagna
city: Palermo
country: Italy
facility: Policlinico Paolo Giaccone /Id# 165663
state: Sicilia
city: Milan
country: Italy
facility: ASST G. Pini /ID# 165715
city: Siena
country: Italy
facility: A.O. Universitaria Senese /ID# 165716
city: Kitakyushu-shi
country: Japan
facility: Hospital of the University of Occupational and Environmental Health /ID# 164380
state: Fukuoka
city: Maebashi-shi
country: Japan
facility: Gunma University Hospital /ID# 165683
state: Gunma
city: Asahikawa-shi
country: Japan
facility: National Hospital Organization Asahikawa Medical Center /ID# 164566
state: Hokkaido
city: Kita-gun
country: Japan
facility: Kagawa University Hospital /ID# 167517
state: Kagawa
city: Nankoku-shi
country: Japan
facility: Kochi Medical School Hospital /ID# 164460
state: Kochi
city: Matsumoto-shi
country: Japan
facility: Shinshu University Hospital /ID# 165304
state: Nagano
city: Okayama-shi
country: Japan
facility: Japanese Red Cross Okayama Hospital /ID# 164376
state: Okayama
city: Kawachinagano-shi
country: Japan
facility: National Hospital Organization Osaka Minami Medical Center /ID# 164365
state: Osaka
city: Osaka-shi
country: Japan
facility: Osaka City University Hospital /ID# 165253
state: Osaka
city: Suita-shi
country: Japan
facility: Osaka University Hospital /ID# 166033
state: Osaka
city: Iruma-gun
country: Japan
facility: Saitama Medical University Hospital /ID# 164577
state: Saitama
city: Koshigaya-shi
country: Japan
facility: Juntendo University Koshigaya Hospital /ID# 165809
state: Saitama
city: Tokushima-shi
country: Japan
facility: Tokushima University Hospital /ID# 165108
state: Tokushima
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital /ID# 164738
state: Tokyo
city: Chuo-ku
country: Japan
facility: St.Luke's International Hospital /ID# 165219
state: Tokyo
city: Nagoya
country: Japan
facility: Daido Hospital /ID# 163886
city: Okayama
country: Japan
facility: Okayama Saiseikai Outpatient Center Hospital /ID# 165595
city: Jung-gu
country: Korea, Republic of
facility: Chungnam National University Hospital /ID# 164561
state: Daejeon Gwang Yeogsi
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center /ID# 165114
state: Incheon Gwang Yeogsi
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital /ID# 164541
state: Jeonranamdo
city: Seongdong-gu
country: Korea, Republic of
facility: Hanyang University Seoul Hospi /ID# 165811
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Cath Univ Seoul St Mary's Hosp /ID# 164549
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Kyunghee University Hospital at Gangdong /ID# 164569
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 164557
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen /ID# 165681
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden /ID# 166937
city: Hamilton
country: New Zealand
facility: Waikato Hospital /ID# 169242
state: Waikato
city: Auckland
country: New Zealand
facility: Middlemore Hospital /ID# 169241
city: Białystok
country: Poland
facility: Osteo-Medic S.C. /ID# 165646
state: Podlaskie
city: Olsztyn
country: Poland
facility: ETYKA-Osrodek Badan Klinicznyc /ID# 165634
state: Warminsko-mazurskie
city: Torun
country: Poland
facility: NZOZ Nasz Lekarz /ID# 166023
city: Lisbon
country: Portugal
facility: Instituto Portugues De Reumatologia /ID# 168314
state: Lisboa
city: Lisbon
country: Portugal
facility: Centro Hospitalar Lisboa Ocidental, EPE /ID# 168312
state: Lisboa
city: Vila Nova De Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova Gaia/Espinho, EPE /ID# 168313
state: Porto
city: Lisbon
country: Portugal
facility: Hospital CUF Descobertas /ID# 168311
city: Viana Do Castelo
country: Portugal
facility: Unidade Local De Saude Do Alto Minho /ID# 168310
city: Santander
country: Spain
facility: Hospital Unversitario Marques de Valdecilla /ID# 165028
state: Cantabria
city: Barcelona
country: Spain
facility: Hospital Parc de Salut del Mar /ID# 165027
city: Barcelona
country: Spain
facility: Corporac Sanitaria Parc Tauli /ID# 165029
city: Malmö
country: Sweden
facility: Skanes Universitetssjukhus /ID# 165712
state: Skane Lan
city: Vaesteras
country: Sweden
facility: Reumatologkliniken /ID# 165713
city: Warrington
country: United Kingdom
facility: Warrington and Halton Hospitals NHS Foundation Trust /ID# 166202
state: Cheshire West And Chester
city: London
country: United Kingdom
facility: Whipps Cross Univ Hospital /ID# 165150
state: London, City Of
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich Univ Hosp /ID# 165149
state: Norfolk
city: Bath
country: United Kingdom
facility: Royal National Hosp for Rheuma /ID# 165147
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary /ID# 165152
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: van der Heijde D, Song IH, Pangan AL, Deodhar A, van den Bosch F, Maksymowych WP, Kim TH, Kishimoto M, Everding A, Sui Y, Wang X, Chu AD, Sieper J. Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial. Lancet. 2019 Dec 7;394(10214):2108-2117. doi: 10.1016/S0140-6736(19)32534-6. Epub 2019 Nov 12.
citation: Deodhar A, van der Heijde D, Sieper J, Van den Bosch F, Maksymowych WP, Kim TH, Kishimoto M, Ostor A, Combe B, Sui Y, Chu AD, Song IH. Safety and Efficacy of Upadacitinib in Patients With Active Ankylosing Spondylitis and an Inadequate Response to Nonsteroidal Antiinflammatory Drug Therapy: One-Year Results of a Double-Blind, Placebo-Controlled Study and Open-Label Extension. Arthritis Rheumatol. 2022 Jan;74(1):70-80. doi: 10.1002/art.41911. Epub 2021 Nov 12.