A Study Evaluating the Safety and Efficacy of Upadacitinib in Adults With Active Ankylosing Spondylitis

NCT ID: NCT03178487

Last Updated: 2023-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 187 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-24
• Study Completion Date: 2022-02-17

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.

Conditions

Ankylosing Spondylitis (AS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Upadacitinib

Intervention Type: DRUG

Tablet

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.

Group Type: PLACEBO_COMPARATOR

Upadacitinib

Intervention Type: DRUG

Tablet

Placebo

Intervention Type: DRUG

Tablet

Interventions

Upadacitinib

Tablet

Intervention Type: DRUG

Placebo

Tablet

Intervention Type: DRUG

Other Intervention Names

ABT-494; RINVOQ™

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

Arizona Arthritis & Rheumatolo /ID# 164446

Phoenix, Arizona, United States

AZ Arthritis and Rheumotology Research, PLLC /ID# 165705

Phoenix, Arizona, United States

David S. Hallegua MD /ID# 165090

Beverly Hills, California, United States

Covina Arthritis Clinic /ID# 165061

Covina, California, United States

St. Joseph Health System /ID# 166166

Fullerton, California, United States

Global Research Foundation /ID# 165130

Los Angeles, California, United States

Rheumatology Center of San Diego /ID# 166167

San Diego, California, United States

Colorado Arthritis Associates /ID# 164444

Lakewood, Colorado, United States

Bay Area Arthritis and Osteo /ID# 165023

Brandon, Florida, United States

LeJenue Research Associates /ID# 165202

Miami, Florida, United States

HMD Research LLC /ID# 205172

Orlando, Florida, United States

St. Lukes Clinic /ID# 165827

Meridian, Idaho, United States

Clinical Investigation Specialists - Skokie /ID# 164385

Skokie, Illinois, United States

Henry Ford Health System /ID# 165515

Detroit, Michigan, United States

Aa Mrc Llc /Id# 165100

Grand Blanc, Michigan, United States

St. Lawrence Health System /ID# 165025

Potsdam, New York, United States

DJL Clinical Research, PLLC /ID# 165044

Charlotte, North Carolina, United States

Altoona Ctr Clinical Res /ID# 164470

Duncansville, Pennsylvania, United States

Clinical Research Ctr Reading /ID# 164876

Wyomissing, Pennsylvania, United States

Comprehensive Arthritis Care, a division of Comprehensive Rheumatology Care PLLC /ID# 168107

Hendersonville, Tennessee, United States

Diagnostic Group Integrated He /ID# 165195

Beaumont, Texas, United States

Arth and Osteo Clin Brazo Valley /ID# 165194

College Station, Texas, United States

Princess Alexandra Hospital /ID# 169239

Woolloongabba, Queensland, Australia

Emeritus Research /ID# 169240

Camberwell, Victoria, Australia

UZ Gent /ID# 166017

Ghent, Oost-Vlaanderen, Belgium

ReumaClinic Genk /ID# 166018

Genk, , Belgium

UZ Leuven /ID# 166019

Leuven, , Belgium

Rheumatology Research Assoc /ID# 165240

Edmonton, Alberta, Canada

University of Alberta - Division of Rheumatology /ID# 165239

Edmonton, Alberta, Canada

Credit Valley Rheumatology /ID# 200087

Mississauga, Ontario, Canada

Groupe de Recherche en Maladies Osseuses Inc /ID# 165238

Sainte-Foy, Quebec, Canada

Clinical Hospital Dubrava /ID# 167049

Zagreb, , Croatia

Medical Center Kuna-Peric /ID# 164851

Zagreb, , Croatia

Revmatologicky ustav Praha /ID# 167004

Prague, Praha 2, Czechia

Thomayerova nemocnice /ID# 167003

Prague, Praha 4, Czechia

REVMACLINIC s.r.o. /ID# 167171

Brno, , Czechia

ARTHROHELP, s.r.o. /ID# 167001

Pardubice, , Czechia

Vejle Sygehus /ID# 165190

Vejle, Region Syddanmark, Denmark

Helsinki Univ Central Hospital /ID# 165794

Helsinki, , Finland

Kiljava Medical Research /ID# 165793

Hyvinkää, , Finland

CHU Bordeaux-Hopital Pellegrin /ID# 166309

Bordeaux, , France

CHRU Tours - Hopital Trousseau /ID# 165109

Chambray-lès-Tours, , France

CHRU de Montpellier - Hôpital Lapeyronie /ID# 166308

Montpellier, , France

Rheumazentrum Ruhrgebiet /ID# 165148

Herne, North Rhine-Westphalia, Germany

Kerckhoff Klinik GmbH /ID# 165158

Bad Nauheim, , Germany

Charite - Campus Benjamin Franklin Medizinische Klinik - Rheumatologie /ID# 165153

Berlin, , Germany

Hamburger Rheuma Forschungszentrum II im MVZ Rheumatologie und Autoimmunmedizin /ID# 165146

Hamburg, , Germany

Revita Reumatologiai Rendelo /ID# 164724

Budapest, , Hungary

University of Debrecen /ID# 165674

Debrecen, , Hungary

Vita Verum Medical Bt. /ID# 165066

Székesfehérvár, , Hungary

Vital Medical Center Orvosi-es Fogaszati Kozpont /ID# 164741

Veszprém, , Hungary

Ospedale Sant Orsola Malpighi /ID# 165692

Bologna, Emilia-Romagna, Italy

Policlinico Paolo Giaccone /Id# 165663

Palermo, Sicily, Italy

ASST G. Pini /ID# 165715

Milan, , Italy

A.O. Universitaria Senese /ID# 165716

Siena, , Italy

Hospital of the University of Occupational and Environmental Health /ID# 164380

Kitakyushu-shi, Fukuoka, Japan

Gunma University Hospital /ID# 165683

Maebashi, Gunma, Japan

National Hospital Organization Asahikawa Medical Center /ID# 164566

Asahikawa-shi, Hokkaido, Japan

Kagawa University Hospital /ID# 167517

Kita-gun, Kagawa-ken, Japan

Kochi Medical School Hospital /ID# 164460

Nankoku-shi, Kochi, Japan

Shinshu University Hospital /ID# 165304

Matsumoto-shi, Nagano, Japan

Japanese Red Cross Okayama Hospital /ID# 164376

Okayama, Okayama-ken, Japan

National Hospital Organization Osaka Minami Medical Center /ID# 164365

Kawachinagano-shi, Osaka, Japan

Osaka City University Hospital /ID# 165253

Osaka, Osaka, Japan

Osaka University Hospital /ID# 166033

Suita-shi, Osaka, Japan

Saitama Medical University Hospital /ID# 164577

Iruma-gun, Saitama, Japan

Juntendo University Koshigaya Hospital /ID# 165809

Koshigaya-shi, Saitama, Japan

Tokushima University Hospital /ID# 165108

Tokushima, Tokushima, Japan

Juntendo University Hospital /ID# 164738

Bunkyo-ku, Tokyo, Japan

St.Luke's International Hospital /ID# 165219

Chuo-ku, Tokyo, Japan

Daido Hospital /ID# 163886

Nagoya, , Japan

Okayama Saiseikai Outpatient Center Hospital /ID# 165595

Okayama, , Japan

Universitair Medisch Centrum Groningen /ID# 165681

Groningen, , Netherlands

Medisch Centrum Leeuwarden /ID# 166937

Leeuwarden, , Netherlands

Waikato Hospital /ID# 169242

Hamilton, Waikato Region, New Zealand

Middlemore Hospital /ID# 169241

Auckland, , New Zealand

Osteo-Medic S.C. /ID# 165646

Bialystok, Podlaskie Voivodeship, Poland

ETYKA-Osrodek Badan Klinicznyc /ID# 165634

Olsztyn, Warmian-Masurian Voivodeship, Poland

NZOZ Nasz Lekarz /ID# 166023

Torun, , Poland

Instituto Portugues De Reumatologia /ID# 168314

Lisbon, Lisbon District, Portugal

Centro Hospitalar Lisboa Ocidental, EPE /ID# 168312

Lisbon, Lisbon District, Portugal

Centro Hospitalar de Vila Nova Gaia/Espinho, EPE /ID# 168313

Vila Nova de Gaia, Porto District, Portugal

Hospital CUF Descobertas /ID# 168311

Lisbon, , Portugal

Unidade Local De Saude Do Alto Minho /ID# 168310

Viana do Castelo, , Portugal

Chungnam National University Hospital /ID# 164561

Junggu, Daejeon Gwang Yeogsi, South Korea

Gachon University Gil Medical Center /ID# 165114

Incheon, Incheon Gwang Yeogsi, South Korea

Chonnam National University Hospital /ID# 164541

Gwangju, Jeonranamdo, South Korea

Hanyang University Seoul Hospi /ID# 165811

Seongdong-gu, Seoul Teugbyeolsi, South Korea

Cath Univ Seoul St Mary's Hosp /ID# 164549

Seoul, Seoul Teugbyeolsi, South Korea

Kyunghee University Hospital at Gangdong /ID# 164569

Seoul, , South Korea

Asan Medical Center /ID# 164557

Seoul, , South Korea

Hospital Unversitario Marques de Valdecilla /ID# 165028

Santander, Cantabria, Spain

Hospital Parc de Salut del Mar /ID# 165027

Barcelona, , Spain

Corporac Sanitaria Parc Tauli /ID# 165029

Barcelona, , Spain

Skanes Universitetssjukhus /ID# 165712

Malmo, Skåne County, Sweden

Reumatologkliniken /ID# 165713

Västerås, , Sweden

Warrington and Halton Hospitals NHS Foundation Trust /ID# 166202

Warrington, Cheshire West And Chester, United Kingdom

Whipps Cross Univ Hospital /ID# 165150

London, London, City of, United Kingdom

Norfolk and Norwich Univ Hosp /ID# 165149

Norwich, Norfolk, United Kingdom

Royal National Hosp for Rheuma /ID# 165147

Bath, , United Kingdom

Glasgow Royal Infirmary /ID# 165152

Glasgow, , United Kingdom

Countries

United States; Australia; Belgium; Canada; Croatia; Czechia; Denmark; Finland; France; Germany; Hungary; Italy; Japan; Netherlands; New Zealand; Poland; Portugal; South Korea; Spain; Sweden; United Kingdom

References

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-000431-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M16-098

Identifier Type: -

Identifier Source: org_study_id