A Phase 3, Randomized, Double-Blind, Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Subjects With Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Non-Biologic Disease Modifying Anti-Rheumatic Drug (DMARD) - SELECT - PsA 1
A Phase 3, Randomized, Double-Blind, Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Subjects With Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Non-Biologic Disease Modifying Anti-Rheumatic Drug (DMARD) - SELECT - PsA 1
This study includes two periods. The main objective of Period 1 is to compare the efficacy of upadacitinib 15 mg once daily (QD) and 30 mg QD versus placebo and versus adalimumab (Humira®) in participants with moderately to severely active psoriatic arthritis (PsA) who have had an inadequate response to non-biologic DMARDs (DMARD-IR). Period 1 is also designed to compare the efficacy of upadacitinib 15 mg and 30 mg QD versus placebo for the prevention of structural progression.
The objective of Period 2 is to evaluate the long-term safety, tolerability and efficacy of upadacitinib 15 mg and 30 mg QD in participants who have completed Period 1.
The study includes a 35-day screening period, a 56-week blinded period (Period 1), a long-term extension period of up to a total treatment duration of approximately 5 years (Period 2), a 30-day follow-up call or visit, and a 70-day follow-up call.
Period 1 includes 24 weeks of randomized, double-blind, placebo-controlled and active comparator-controlled treatment followed by 32 weeks of active comparator-controlled upadacitinib; at Week 24 participants assigned to placebo will be switched to upadacitinib according to their randomization assignment.
Participants who meet eligibility criteria will be randomized in a 2:2:2:1:1 ratio to one of five treatment groups:
Randomization will be stratified by extent of psoriasis (≥ 3% body surface area [BSA] or < 3% BSA), current use of at least 1 non-biologic DMARD, presence of dactylitis, and presence of enthesitis, except for participants from China and Japan, where randomization for each country will be stratified by extent of psoriasis (≥ 3% BSA or < 3% BSA) only.
Participants who complete the Week 56 visit (end of Period 1) will enter the long-term extension portion of the study, Period 2 (total treatment up to approximately 5 years), and continue study treatment as assigned in Period 1 in a blinded manner until the last subject completes the last visit of Period 1 (Week 56), when study drug assignment in both periods will be unblinded and participants will be dispensed study drug in an open-label fashion until the completion of Period 2.
At Week 16, rescue therapy will be offered to participants classified as non-responders (defined as not achieving at least 20% improvement in tender joint count (TJC) and / or swollen joint count (SJC) at both Week 12 and Week 16). Starting at Week 36, participants who fail to demonstrate at least 20% improvement in either or both TJC and SJC compared to Baseline at 2 consecutive visits will be discontinued from study drug treatment. Additionally, in participants continuing on study drug, starting at the Week 36 visit, initiation of or change in background PsA medication(s) is allowed as per local label.
Inclusion Criteria:
Clinical diagnosis of PsA with symptom onset at least 6 months prior to the Screening Visit and fulfillment of the Classification Criteria for PsA (CASPAR) criteria.
Participant has active disease at Baseline defined as >= 3 tender joints (based on 68 joint counts) and >= 3 swollen joints (based on 66 joint counts) at Screening and Baseline Visits.
Presence of either at Screening:
Diagnosis of active plaque psoriasis or documented history of plaque psoriasis.
Participant has had an inadequate response (lack of efficacy after a minimum 12 week duration of therapy) to previous or current treatment with at least 1 non-biologic DMARD at maximally tolerated dose (methotrexate (MTX), sulfasalazine (SSZ), leflunomide (LEF), cyclosporine, apremilast, bucillamin or iguratimod), or participant has an intolerance to or contraindication for DMARDs as defined by the investigator.
Participant who is on current treatment with concomitant non-biologic DMARDs at study entry must be on <= 2 non-biologic DMARDs (except the combination of MTX and leflunomide). The following non-biologic DMARDs are allowed: MTX, sulfasalazine, leflunomide, apremilast, hydroxychloroquine (HCQ) , bucillamine or iguratimod, and have been ongoing for >= 12 weeks and at stable dose for >= 4 weeks prior to the Baseline Visit. No other DMARDs are permitted during the study.
i. Participants who need to discontinue DMARDs prior to the Baseline Visit to comply with this inclusion criterion must follow the procedure specified below or at least five times the mean terminal elimination half-life of a drug:
>= 8 weeks for LEF if no elimination procedure was followed, or adhere to an elimination procedure (i.e., 11 days with cholestyramine, or 30 days washout with activated charcoal or as per local label);
>= 4 weeks for all others.
Exclusion Criteria:
Prior exposure to any Janus Kinase (JAK) inhibitor (including but not limited to ruxolitinib, tofacitinib, baricitinib, and filgotinib).
Current treatment with > 2 non-biologic DMARDs; or use of DMARDs other than methotrexate, sulfasalazine, leflunomide, apremilast, hydroxychloroquine, bucillamine, or iguratimod; or use of methotrexate in combination with leflunomide.
History of fibromyalgia, any arthritis with onset prior to age 17 years, or current diagnosis of inflammatory joint disease other than PsA (including, but not limited to rheumatoid arthritis, gout, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, systemic lupus erythematosus). Prior history of reactive arthritis or axial spondyloarthritis including ankylosing spondylitis and nonradiographic axial spondyloarthritis is permitted if documentation of change in diagnosis to PsA or additional diagnosis of PsA is made. Prior history of fibromyalgia is permitted if documentation of change in diagnosis to PsA or documentation that the diagnosis of fibromyalgia was made incorrectly.
St Louis, Missouri 63119-3845, United States
Summerville, South Carolina 29486-7887, United States
San Miguel de Tucumán, Ciuadad Autonoma de Buenos Aires 4000, Argentina
San Miguel de Tucumán, Tucumán Province 4000, Argentina
CABA, 1428, Argentina
Rosario, Santa FE, 2000, Argentina
Banja Luka, Republika Srpska 78000, Bosnia and Herzegovina
Porto Alegre, Rio Grande do Sul 90035-001, Brazil
Ribeirão Preto, São Paulo 14049-900, Brazil
Santo André, São Paulo 09190-510, Brazil
Sofia, 1606, Bulgaria
Vitacura Santiago, 7640881, Chile
Shantou, Guangdong 515041, China
Baotou, Inner Mongolia 014016, China
Bogota, Cundinamarca 110231, Colombia
Uherské Hradište, 686 01, Czechia
Hamburg, 20095, Germany
Budapest III, Pest County 1036, Hungary
Nyíregyháza, Szabolcs-Szatmár-Bereg 4400, Hungary
Reggio Emilia, Emilia-Romagna 42123, Italy
Catania, 95123, Italy
Kitakyushu-shi, Fukuoka 807-8556, Japan
Kawachinagano-shi, Osaka 586-8521, Japan
Chuo-ku, Tokyo 104-8560, Japan
Mexico City, Mexico City 11850, Mexico
Gdansk, Pomeranian Voivodeship 80-382, Poland
Vila Nova de Gaia, Porto District 4434-502, Portugal
Korolev, Moscow 141060, Russia
Pieštany, 921 01, Slovakia
Saricam Adana, Adana 01330, Turkey (Türkiye)
Sihhiye, Ankara 06100, Turkey (Türkiye)
Istanbul, 34899, Turkey (Türkiye)
Meram Konya, 42080, Turkey (Türkiye)
Kharkiv, Kharkiv Oblast 61039, Ukraine