A Study With Upadacitinib (ABT-494) in Subjects From China and Selected Countries With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs)
Condition: Rheumatoid Arthritis (RA)
MeSH terms: Arthritis; Arthritis, Rheumatoid; Rheumatic Diseases
Intervention: Upadacitinib; Placebo
Intervention description: Tablets for oral administration; Tablets for oral administration
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: 338.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rheumatoid Arthritis; Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs); ABT-494

Summary:

      The study objectives of Period 1 of this study were to compare the efficacy, safety, and
      tolerability of upadacitinib versus placebo for the treatment of signs and symptoms of
      subjects from China and selected countries including Brazil and South Korea with moderately
      to severely active rheumatoid arthritis (RA) who are on a stable dose of csDMARDs and have an
      inadequate response to csDMARDs.

      The study objective of Period 2 is to evaluate the long-term safety, tolerability, and
      efficacy of upadacitinib in subjects with RA who have completed Period 1.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of RA for ≥ 3 months who also fulfill the 2010 American College of
             Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification criteria
             for RA.

          -  Participants have been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥
             4 weeks prior to the first dose of study drug.

               1. Participants must have failed (lack of efficacy) at least one of the following:
                  methotrexate (MTX), sulfasalazine, or leflunomide.

               2. The following csDMARDs are allowed: oral or parenteral MTX, sulfasalazine,
                  hydroxychloroquine, chloroquine, and leflunomide.

               3. A combination of up to two background csDMARDs is allowed except the combination
                  of MTX and leflunomide.

          -  Participant meets both of the following disease activity criteria:

               1. ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68
                  joint counts) at Screening and Baseline Visits; and

               2. High-sensitivity C-Reactive Protein (hsCRP) ≥ 3 mg/L at Screening

          -  Participants with prior exposure to at most one biological disease-modifying
             anti-rheumatic drugs (bDMARD) may be enrolled (up to 20% of total number of subjects).
             Specifically, prior to enrollment:

               1. Participants with limited exposure to bDMARD (< 3 months) OR

               2. Participants who are responding to a bDMARD therapy but had to discontinue due to
                  intolerability (regardless of treatment duration).

          -  Participants must have discontinued bDMARD therapy prior to the first dose of study
             drug.

        Exclusion Criteria:

          -  Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to
             tofacitinib, baricitinib, and filgotinib).

          -  Participants who are considered inadequate responders (lack of efficacy) to bDMARD
             therapy as defined by the Investigator.

          -  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.