A Study to Compare Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis on Stable Dose of Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) With an Inadequate Response or Intolerance to Biologic DMARDs
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Placebo; Upadacitinib
Intervention description: Tablet; Oral; Tablet; Oral
Intervention MeSH terms: 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: 499.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Musculoskeletal Disease; Arthritis; Joint Disease; Anti-inflammatory agents; Antirheumatic agents; ABT-494; upadacitinib

Summary:

      The study objective of Period 1 (Day 1 to Week 24) is to compare the safety and efficacy of
      upadacitinib 30 mg once daily (QD) and 15 mg QD versus placebo for the treatment of signs and
      symptoms of participants with moderately to severely active rheumatoid arthritis (RA) who are
      on a stable dose of csDMARDs and had an inadequate response to or intolerance to at least 1
      bDMARD.

      The study objective of Period 2 (Week 24 to Week 260) is to evaluate the long-term safety,
      tolerability, and efficacy of upadacitinib 15 mg QD and 30 mg QD in participants with RA who
      completed Period 1.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of rheumatoid arthritis (RA) for≥ 3 months.

          -  Treated for ≥ 3 months with ≥ 1 bDMARD therapy, but continue to exhibit active RA or
             had to discontinue due to intolerability or toxicity, irrespective of treatment
             duration prior to the first dose of study drug.

          -  Participant has been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥ 4
             weeks prior to the first dose of study drug. The following csDMARDs are allowed:
             methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide. A
             combination of up to two background csDMARDs is allowed except the combination of MTX
             and leflunomide.

          -  Meets both of the following criteria:

          -  ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint
             counts) at Screening and Baseline Visits.

          -  hsCRP ≥ 3mg/L at Screening Visit.

        Exclusion Criteria:

          -  Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to
             tofacitinib, baricitinib, and filgotinib).

          -  History of any arthritis with onset prior to age 17 years or current diagnosis of
             inflammatory joint disease other than RA (including but not limited to gout, systemic
             lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing
             spondylitis and non-radiographic axial spondyloarthritis, reactive arthritis, overlap
             connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia
             [currently with active symptoms]). Current diagnosis of secondary Sjogren's Syndrome
             is permitted.