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
Study type: Interventional
Phase: Phase 3

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.
    

Detailed description: 
      This study includes a 35-day screening period; a 24-week randomized, double-blind,
      parallel-group, placebo controlled treatment period (Period 1); a 236-week blinded long-term
      extension period (Period 2); and a 30-day follow-up period (call or visit).

      Period 1 consists of a 12-week double-blind, placebo-controlled treatment phase plus a
      12-week double-blind phase where all participants were to receive upadacitinib; at Week 12
      participants assigned to placebo will be switched to upadacitinib according to their
      randomization assignment.

      Participants who meet eligibility criteria will be randomized in a 2:2:1:1 ratio to one of
      four treatment groups:

        -  Group 1: Upadacitinib 30 mg QD (Day 1 to Week 12) → upadacitinib 30 mg QD (Week 12 and
           thereafter)

        -  Group 2: Upadacitinib 15 mg QD (Day 1 to Week 12) → upadacitinib 15 mg QD (Week 12 and
           thereafter)

        -  Group 3: Placebo (Day 1 to Week 12) → upadacitinib 30 mg QD (Week 12 and thereafter)

        -  Group 4: Placebo (Day 1 to Week 12) → upadacitinib 15 mg QD (Week 12 and thereafter)

      Participants will continue stable dose of csDMARD therapy for the first 24 weeks of the
      study.

      Participants who complete the Week 24 visit (end of Period 1) will enter the blinded
      long-term extension portion of the study, Period 2 and continue to receive the same dose of
      upadacitinib per original randomization assignment in a blinded manner. Starting at Week 24,
      at least 20% improvement in both swollen joint count (SJC) and tender joint count (TJC)
      compared to Baseline is required to remain on study drug. Starting at Week 24, initiation of
      or change in corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen,
      or adding or increasing doses in up to 2 csDMARDs (concomitant use of up to 2 csDMARDs except
      the combination of methotrexate and leflunomide) is allowed as per local label.

      With the implementation of Protocol Amendment 4, all participants in the extension period
      will receive open-label upadacitinib 15 mg QD, including those currently on upadacitinib 30
      mg QD.
    

Intervention name(s): Placebo; Upadacitinib
Intervention type(s): Drug; Drug
Intervention description(s): Tablet; Oral; Tablet; Oral
Other intervention name(s): ABT-494; RINVOQ®
Intervention MeSH terms: Upadacitinib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Musculoskeletal Disease; Arthritis; Joint Disease; Anti-inflammatory agents; Antirheumatic agents; ABT-494; upadacitinib