A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Participants With Psoriatic Arthritis Who Have an Inadequate Response to at Least One Non-Biologic Disease Modifying Anti-Rheumatic Drug (DMARD)
Condition: Psoriatic Arthritis
MeSH terms: Arthritis; Arthritis, Psoriatic; Rheumatic Diseases
Intervention: Adalimumab; Upadacitinib; Placebo to Upadacitinib; Placebo to Adalimumab
Intervention description: Administered by subcutaneous injection; Oral tablet; Oral tablet; Administered by subcutaneous injection
Intervention MeSH terms: Adalimumab; Upadacitinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1705.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Arthritis; Psoriasis; Anti-inflammatory; Joint disease; Musculoskeletal disease; Anti-Rheumatic

Summary:

      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.
    

Eligibility criteria:

        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:

               1. >= 1 erosion on x-ray as determined by central imaging review or;

               2. high-sensitivity C-reactive protein (hs-CRP) > laboratory defined upper limit of
                  normal (ULN).

          -  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:

               1. >= 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);

               2. >= 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.