A Study Evaluating the Safety and Efficacy of Upadacitinib in Adults With Active Ankylosing Spondylitis (SELECT-AXIS 1)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis

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).

Study Overview

• Status: Completed
• Conditions: Ankylosing Spondylitis (AS)
• Intervention / Treatment: Drug: Placebo; Drug: Upadacitinib

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.

• Study Type: Interventional
• Enrollment (Actual): 187
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital /ID# 169239
  • Victoria
    • Camberwell, Victoria, Australia, 3124
      • Emeritus Research /ID# 169240
• Belgium
  • Genk, Belgium, 3600
    • ReumaClinic Genk /ID# 166018
  • Leuven, Belgium, 3000
    • UZ Leuven /ID# 166019
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent /ID# 166017
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5M 0H4
      • Rheumatology Research Assoc /ID# 165240
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta - Division of Rheumatology /ID# 165239
  • Ontario
    • Mississauga, Ontario, Canada, L5M 2V8
      • Credit Valley Rheumatology /ID# 200087
  • Quebec
    • Sainte-foy, Quebec, Canada, G1V 3M7
      • Groupe de Recherche en Maladies Osseuses Inc /ID# 165238
• Croatia
  • Zagreb, Croatia, 10000
    • Clinical Hospital Dubrava /ID# 167049
  • Zagreb, Croatia, 10000
    • Medical Center Kuna-Peric /ID# 164851
• Czechia
  • Brno, Czechia, 611 41
    • REVMACLINIC s.r.o. /ID# 167171
  • Pardubice, Czechia, 530 02
    • ARTHROHELP, s.r.o. /ID# 167001
  • Praha 2
    • Prague 2, Praha 2, Czechia, 128 00
      • Revmatologicky ustav Praha /ID# 167004
  • Praha 4
    • Prague 4, Praha 4, Czechia, 140 00
      • Thomayerova nemocnice /ID# 167003
• Denmark
  • Syddanmark
    • Vejle, Syddanmark, Denmark, 7100
      • Vejle Sygehus /ID# 165190
• Finland
  • Helsinki, Finland, 00290
    • Helsinki Univ Central Hospital /ID# 165794
  • Hyvinkaa, Finland, 05800
    • Kiljava Medical Research /ID# 165793
• France
  • Bordeaux, France, 33076
    • CHU Bordeaux-Hopital Pellegrin /ID# 166309
  • Chambray Les Tours, France, 37170
    • CHRU Tours - Hopital Trousseau /ID# 165109
  • Montpellier, France, 34090
    • CHRU de Montpellier - Hôpital Lapeyronie /ID# 166308
• Germany
  • Bad Nauheim, Germany, 61231
    • Kerckhoff Klinik GmbH /ID# 165158
  • Berlin, Germany, 12203
    • Charite - Campus Benjamin Franklin Medizinische Klinik - Rheumatologie /ID# 165153
  • Hamburg, Germany, 20095
    • Hamburger Rheuma Forschungszentrum II im MVZ Rheumatologie und Autoimmunmedizin /ID# 165146
  • Nordrhein-Westfalen
    • Herne, Nordrhein-Westfalen, Germany, 44649
      • Rheumazentrum Ruhrgebiet /ID# 165148
• Hungary
  • Budapest, Hungary, 1027
    • Revita Reumatologiai Rendelo /ID# 164724
  • Debrecen, Hungary, 4032
    • University of Debrecen /ID# 165674
  • Szekesfehervar, Hungary, 8000
    • Vita Verum Medical Bt. /ID# 165066
  • Veszprem, Hungary, 8200
    • Vital Medical Center Orvosi-es Fogaszati Kozpont /ID# 164741
• Italy
  • Milan, Italy, 20122
    • ASST G. Pini /ID# 165715
  • Siena, Italy, 53100
    • A.O. Universitaria Senese /ID# 165716
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Ospedale Sant Orsola Malpighi /ID# 165692
  • Sicilia
    • Palermo, Sicilia, Italy, 90127
      • Policlinico Paolo Giaccone /Id# 165663
• Japan
  • Nagoya, Japan, 457-8511
    • Daido Hospital /ID# 163886
  • Okayama, Japan, 700-0013
    • Okayama Saiseikai Outpatient Center Hospital /ID# 165595
  • Fukuoka
    • Kitakyushu-shi, Fukuoka, Japan, 807-8556
      • Hospital of the University of Occupational and Environmental Health /ID# 164380
  • Gunma
    • Maebashi-shi, Gunma, Japan, 371-8511
      • Gunma University Hospital /ID# 165683
  • Hokkaido
    • Asahikawa-shi, Hokkaido, Japan, 070-8644
      • National Hospital Organization Asahikawa Medical Center /ID# 164566
  • Kagawa
    • Kita-gun, Kagawa, Japan, 761-0793
      • Kagawa University Hospital /ID# 167517
  • Kochi
    • Nankoku-shi, Kochi, Japan, 783-8505
      • Kochi Medical School Hospital /ID# 164460
  • Nagano
    • Matsumoto-shi, Nagano, Japan, 390-8621
      • Shinshu University Hospital /ID# 165304
  • Okayama
    • Okayama-shi, Okayama, Japan, 7008607
      • Japanese Red Cross Okayama Hospital /ID# 164376
  • Osaka
    • Kawachinagano-shi, Osaka, Japan, 586-8521
      • National Hospital Organization Osaka Minami Medical Center /ID# 164365
    • Osaka-shi, Osaka, Japan, 545-8586
      • Osaka City University Hospital /ID# 165253
    • Suita-shi, Osaka, Japan, 565-0871
      • Osaka University Hospital /ID# 166033
  • Saitama
    • Iruma-gun, Saitama, Japan, 350-0451
      • Saitama Medical University Hospital /ID# 164577
    • Koshigaya-shi, Saitama, Japan, 343-0032
      • Juntendo University Koshigaya Hospital /ID# 165809
  • Tokushima
    • Tokushima-shi, Tokushima, Japan, 770-8503
      • Tokushima University Hospital /ID# 165108
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Juntendo University Hospital /ID# 164738
    • Chuo-ku, Tokyo, Japan, 104-8560
      • St.Luke's International Hospital /ID# 165219
• Korea, Republic of
  • Seoul, Korea, Republic of, 02447
    • Kyunghee University Hospital at Gangdong /ID# 164569
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center /ID# 164557
  • Daejeon Gwang Yeogsi
    • Jung-gu, Daejeon Gwang Yeogsi, Korea, Republic of, 35015
      • Chungnam National University Hospital /ID# 164561
  • Incheon Gwang Yeogsi
    • Incheon, Incheon Gwang Yeogsi, Korea, Republic of, 21565
      • Gachon University Gil Medical Center /ID# 165114
  • Jeonranamdo
    • Gwangju, Jeonranamdo, Korea, Republic of, 61469
      • Chonnam National University Hospital /ID# 164541
  • Seoul Teugbyeolsi
    • Seongdong-gu, Seoul Teugbyeolsi, Korea, Republic of, 04763
      • Hanyang University Seoul Hospi /ID# 165811
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06591
      • Cath Univ Seoul St Mary's Hosp /ID# 164549
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen /ID# 165681
  • Leeuwarden, Netherlands, 8934 AD
    • Medisch Centrum Leeuwarden /ID# 166937
• New Zealand
  • Auckland, New Zealand, 2025
    • Middlemore Hospital /ID# 169241
  • Waikato
    • Hamilton, Waikato, New Zealand, 3204
      • Waikato Hospital /ID# 169242
• Poland
  • Torun, Poland, 87-100
    • NZOZ Nasz Lekarz /ID# 166023
  • Podlaskie
    • Białystok, Podlaskie, Poland, 15-351
      • Osteo-Medic S.C. /ID# 165646
  • Warminsko-mazurskie
    • Olsztyn, Warminsko-mazurskie, Poland, 10-117
      • ETYKA-Osrodek Badan Klinicznyc /ID# 165634
• Portugal
  • Lisbon, Portugal, 1998-018
    • Hospital CUF Descobertas /ID# 168311
  • Viana Do Castelo, Portugal, 4901-858
    • Unidade Local De Saude Do Alto Minho /ID# 168310
  • Lisboa
    • Lisbon, Lisboa, Portugal, 1050-034
      • Instituto Portugues De Reumatologia /ID# 168314
    • Lisbon, Lisboa, Portugal, 1349-019
      • Centro Hospitalar Lisboa Ocidental, EPE /ID# 168312
  • Porto
    • Vila Nova De Gaia, Porto, Portugal, 4434-502
      • Centro Hospitalar de Vila Nova Gaia/Espinho, EPE /ID# 168313
• Spain
  • Barcelona, Spain, 08003
    • Hospital Parc de Salut del Mar /ID# 165027
  • Barcelona, Spain, 08006
    • Corporac Sanitaria Parc Tauli /ID# 165029
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Unversitario Marques de Valdecilla /ID# 165028
• Sweden
  • Vaesteras, Sweden, 721 89
    • Reumatologkliniken /ID# 165713
  • Skane Lan
    • Malmö, Skane Lan, Sweden, 214 28
      • Skanes Universitetssjukhus /ID# 165712
• United Kingdom
  • Bath, United Kingdom, BA1 1RL
    • Royal National Hosp for Rheuma /ID# 165147
  • Glasgow, United Kingdom, G4 0SF
    • Glasgow Royal Infirmary /ID# 165152
  • Cheshire West And Chester
    • Warrington, Cheshire West And Chester, United Kingdom, WA5 1QG
      • Warrington and Halton Hospitals NHS Foundation Trust /ID# 166202
  • London, City Of
    • London, London, City Of, United Kingdom, E11 1NR
      • Whipps Cross Univ Hospital /ID# 165150
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7UY
      • Norfolk and Norwich Univ Hosp /ID# 165149
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032-9306
      • Arizona Arthritis & Rheumatolo /ID# 164446
    • Phoenix, Arizona, United States, 85032-9306
      • AZ Arthritis and Rheumotology Research, PLLC /ID# 165705
  • California
    • Beverly Hills, California, United States, 90211
      • David S. Hallegua MD /ID# 165090
    • Covina, California, United States, 91722
      • Covina Arthritis Clinic /ID# 165061
    • Fullerton, California, United States, 92835
      • St. Joseph Health System /ID# 166166
    • Los Angeles, California, United States, 90041
      • Global Research Foundation /ID# 165130
    • San Diego, California, United States, 92128-2549
      • Rheumatology Center of San Diego /ID# 166167
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Colorado Arthritis Associates /ID# 164444
  • Florida
    • Brandon, Florida, United States, 33511
      • Bay Area Arthritis and Osteo /ID# 165023
    • Miami, Florida, United States, 33126
      • LeJenue Research Associates /ID# 165202
    • Orlando, Florida, United States, 32819
      • HMD Research LLC /ID# 205172
  • Idaho
    • Meridian, Idaho, United States, 83642
      • St. Lukes Clinic /ID# 165827
  • Illinois
    • Skokie, Illinois, United States, 60076
      • Clinical Investigation Specialists - Skokie /ID# 164385
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System /ID# 165515
    • Grand Blanc, Michigan, United States, 48439
      • Aa Mrc Llc /Id# 165100
  • New York
    • Potsdam, New York, United States, 13676
      • St. Lawrence Health System /ID# 165025
  • North Carolina
    • Charlotte, North Carolina, United States, 28210-8508
      • DJL Clinical Research, PLLC /ID# 165044
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Ctr Clinical Res /ID# 164470
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research Ctr Reading /ID# 164876
  • Tennessee
    • Hendersonville, Tennessee, United States, 37075-6213
      • Comprehensive Arthritis Care, a division of Comprehensive Rheumatology Care PLLC /ID# 168107
  • Texas
    • Beaumont, Texas, United States, 77701
      • Diagnostic Group Integrated He /ID# 165195
    • College Station, Texas, United States, 77845
      • Arth and Osteo Clin Brazo Valley /ID# 165194

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Upadacitinib 15 mg; Participants will receive 15 mg upadacitinib orally once a day for 14 weeks in Period 1 and continue to receive 15 mg upadacitinib orally once a day for an additional 90 weeks in Period 2.	Drug: Upadacitinib; Tablet; Other Names: ABT-494; RINVOQ™
Placebo Comparator: Placebo; Participants will receive matching placebo orally once a day for 14 weeks in Period 1. In Period 2 participants will receive 15 mg upadacitinib orally once a day for 90 weeks.	Drug: Placebo; Tablet; Drug: Upadacitinib; Tablet; Other Names: ABT-494; RINVOQ™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 14	ASAS 40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of > 0 units) in the potential remaining domain: Patient's global assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (no activity) to 10 (severe activity);; Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);; Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);; Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).	Baseline and Week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 14	ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula: Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 [none] - 10 [very severe]); Patient global assessment of disease activity (NRS score 0 [no activity] - 10 [severe activity]); Peripheral pain/swelling (BASDAI Question 3; NRS score 0 [none] - 10 [very severe]); Duration of morning stiffness (BASDAI Question 6; NRS score 0 [0 hours] - 10 [2 or more hours]); High-sensitivity C-reactive protein (hs-CRP) in mg/L. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS include Inactive disease (ASDAS < 1.3) and very high disease (ASDAS > 3.5). A negative change from Baseline score indicates improvement in disease activity.	Baseline and Week 14
Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score for the Spine at Week 14	In the SPARCC MRI assessment of the spine, the entire spine is evaluated for active inflammation (bone marrow edema). Six discovertebral units (DVU) representing the 6 most abnormal DVUs were selected to calculate the MRI Spine SPARCC score. For each of the 6 DVUs, 3 consecutive sagittal slices were assessed in 4 quadrants to evaluate the extent of inflammation in all three dimensions. Each quadrant was scored for the presence (1) or absence (0) of edema. If edema was present in at least one quadrant of a DVU slice, it was also scored for intensity and depth of the edema representing that slice: An additional score of 1 was assigned if an intense signal was seen in any quadrant on a DVU slice. Slices that included a lesion demonstrating continuous increased signal of depth ≥ 1 cm extending from the endplate were scored as an additional 1 per slice. The maximum (worst) overall score for all 6 DVUs is 108.	Baseline and Week 14
Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Week 14	The BASDAI assesses disease activity by asking the participant to answer 6 questions (each on an 11 point numeric rating scale [NRS]) pertaining to symptoms experienced for the past week. For Questions 1 to 5 (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (≥ 2 hours). The overall BASDAI score ranges from 0 to 10. Lower scores indicate less disease activity. A BASDAI 50 response is defined as improvement of 50% or more from Baseline in BASDAI score.	Baseline and Week 14
Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score	The ASQoL consists of 18 items related to quality of life, including the impact of pain on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. Each item is answered as yes (scored as 1) or no (scored as 0). Scores are summed to obtain the overall score which ranges from 0 to 18, where higher scores indicate a worse quality of life. A negative change from Baseline in ASQoL indicates improvement in quality of life.	Baseline and Week 14
Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) Partial Remission	ASAS partial remission (PR) is defined as an absolute score of ≤ 2 units on a 0 to 10 scale for each of the four following domains: Patient's global assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (no activity) to 10 (severe activity);; Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);; Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);; Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).	Week 14
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 14	The Bath Ankylosing Spondylitis Functional Index is a validated index to determine the degree of functional limitation in patients with AS. BASFI consists of 10 questions assessing participants' ability to perform activities such as putting on socks, bending, reaching, getting up from the floor or an armless chair, standing, climbing and other physical activities. Each item is scored on a NRS ranging from 0 (easy to perform an activity) to 10 (impossible to perform an activity). The overall score is the mean of the 10 items and ranges from 0 to 10 with higher scores indicating more functional limitations. A negative change from Baseline in BASFI indicates improvement.	Baseline and Week 14
Change From Baseline in Linear Bath Ankylosing Spondylitis Metrology Index (BASMI[Lin]) at Week 14	The BASMI is a composite score based on 5 direct measurements of spinal mobility: cervical rotation (measured in degrees),; tragus to wall distance (in centimeters [cm]); lumbar side flexion (in cm),; lumbar flexion (modified Schober's) (in cm) and; intermalleolar distance (in cm). Each measurement is converted to a linear score between 0 and 10. The total BASMI score is the average of the 5 scores and ranges from 0 to 10; the higher the BASMI score the more severe the patient's limitation of movement due to their ankylosing spondylitis. A negative change from Baseline indicates improvement.	Baseline and Week 14
Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Week 14	The MASES evaluation was conducted to assess the presence or absence of enthesitis (inflammation of the entheses, or sites where tendons or ligaments insert into the bone) at 13 different sites (first costochondral joint left/right, seventh costochondral joint left/right, posterior superior iliac spine left/right, anterior superior iliac spine left/right, iliac crest left/right, fifth lumbar spinous process, and proximal insertion of Achilles tendon left/right. Each site was scored for presence (1) or absence (0) of enthesitis. The MASES is the sum of the 13 site scores, and ranges from 0 to 13, with higher scores indicating more inflammation of the entheses.	Baseline and Week 14
Change From Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment at Week 14	The Work Productivity and Activity Impairment Questionnaire: Axial Spondyloarthritis, Version 2.0 (WPAI-Axial Spondyloarthritis) measures the effect of overall health and specific symptoms on productivity at work and outside of work. It consists of 6 questions. Respondents were asked about time missed from work and time while at work during which productivity was impaired in the past seven days. Results of WPAI are expressed as a percentage of impairment from 0 to 100, with higher percentages indicating greater impairment and less productivity. Overall Work Impairment indicates the percentage of overall work impairment due to health problems. A negative change from Baseline indicates improvement.	Baseline and Week 14
Change From Baseline in ASAS Health Index (HI) at Week 14	The ASAS HI measures functioning and health across 17 aspects of health in patients with AS, including pain, emotional functions, sleep, sexual function, mobility, self care, and community life. Each of the 17 questions is answered by the participant as "I agree" (score = 1) or "I disagree" (score = 0). The responses to the 17 dichotomous items are summed up to give a total score ranging from 0 to 17, where a higher score indicates a worse health status. A negative change from Baseline indicates improvement.	Baseline and Week 14
Percentage of Participants Achieving an ASAS 20 Response at Week 14	ASAS 20 response was defined as an improvement of ≥ 20% and an absolute improvement of ≥ 1 unit (on a scale of 0 to 10) from Baseline in at least 3 of the following 4 domains, with no deterioration (defined as a worsening of ≥ 20% and a net worsening of ≥ 1 units [on a scale of 0 to 10]) in the remaining domain: Patient's global assessment of disease activity, measured on a NRS from 0 (no activity) to 10 (severe activity);; Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);; Function, measured by the BASFI which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);; Inflammation, measured by the mean of the 2 morning stiffness-related BASDAI NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).	Baseline and Week 14
Change From Baseline in SPARCC MRI Score for Sacroiliac Joints at Week 14	In the SPARCC MRI assessment of the sacroiliac (SI) joints 6 consecutive sacroiliac joint image coronal slices representing the largest proportion of the synovial compartment of the SI joints were assessed for edema, intensity and depth of edema. Each SI joint (left and right) was divided into quadrants for a total of 8 SI scoring locations. Each quadrant was scored for the presence (1) or absence (0) of edema, intensity of edema (a score of 1 was assigned for each SI joint (left and right) if an intense signal was seen in any quadrant of that joint for each slice), and a lesion was graded as deep (score of 1) if there was homogeneous and unequivocal increase in signal extending over a depth of at least 1 cm from the articular surface of the SI joint in any quadrant. The total maximum score for all SI joints across 6 slices is 72.	Baseline and Week 14

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2017
• Primary Completion (Actual): January 21, 2019
• Study Completion (Actual): February 17, 2022

Study Registration Dates

• First Submitted: June 5, 2017
• First Submitted That Met QC Criteria: June 5, 2017
• First Posted (Actual): June 7, 2017

Study Record Updates

• Last Update Posted (Estimate): March 7, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Upadacitinib; ABT-494; Ankylosing Spondylitis (AS)
• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Janus Kinase Inhibitors; Upadacitinib
• Other Study ID Numbers: M16-098; 2017-000431-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No