A Study to Evaluate Efficacy and Safety of Upadacitinib in Adults With Axial Spondyloarthritis
Condition: Spondyloarthritis
MeSH terms: Spondylitis; Spondylarthritis; Axial Spondyloarthritis
Intervention: Upadacitinib; Placebo
Intervention description: Upadacitinib tablet administered orally; Placebo for upadacitinib tablet administered orally
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: 734.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Upadacitinib; Axial Spondyloarthritis (axSpA); Spondyloarthritis; Ankylosing Spondylitis (AS)

Summary:

      This protocol includes 2 standalone studies with randomization, data collection, analysis and
      reporting conducted independently.

      The main objectives of this protocol are:

        -  To evaluate the efficacy of upadacitinib compared with placebo on reduction of signs and
           symptoms in adults with active axial spondyloarthritis (axSpA) including biologic
           disease-modifying antirheumatic drug inadequate responders (bDMARD-IR) ankylosing
           spondylitis (AS) (Study 1) and non-radiographic axial spondyloarthritis (nr-axSpA)
           (Study 2).

        -  To assess the safety and tolerability of upadacitinib in adults with active axSpA
           including bDMARD-IR AS (Study 1) and nr-axSpA (Study 2).

        -  To evaluate the safety and tolerability of upadacitinib in extended treatment in adult
           participants with active axSpA including bDMARD-IR AS who have completed the
           Double-Blind Period (Study 1) and nr-axSpA who have completed the Double-Blind Period
           (Study 2).

        -  To evaluate the maintenance of disease control after withdrawal of upadacitinib.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Study 1:

               -  Must have a clinical diagnosis of ankylosing spondylitis (AS) and meet the
                  modified New York Criteria for AS,

               -  Must not have total spinal ankylosis

               -  Must have been previously exposed to 1 or 2 bDMARDs (at least 1 tumor necrosis
                  factor [TNF] inhibitor or 1 interleukin [IL]-17 inhibitor [IL-17i]), and must
                  have discontinued the bDMARD therapy due to either lack of efficacy (after at
                  least 12 weeks of treatment with a bDMARD at an adequate dose) or intolerance
                  (irrespective of treatment duration). Prior exposure to two bDMARDs was allowed
                  for no more than 30% of patients; among patients with prior exposure to two
                  bDMARDs, a lack of efficacy to one bDMARD and intolerance to another was
                  permitted, but a patient could not have a lack of efficacy to two bDMARDs

          -  Study 2:

               -  Must have a clinical diagnosis of nr-axSpA fulfilling the 2009 Assessment of
                  SpondyloArthritis international Society (ASAS) classification criteria for axSpA
                  but not meeting the radiologic criterion of the modified New York criteria for AS

               -  Must have objective signs of active inflammation consistent with axSpA on
                  magnetic resonance imaging (MRI) of sacroiliac (SI) joints or based on high
                  sensitivity C-reactive protein (hsCRP) > the upper limit of normal (ULN).

               -  Prior treatment with at most one bDMARD (either TNF inhibitor or IL-17i) is
                  allowed for at least 20% but no more than 35% of enrolled patients who had to
                  discontinue the prior bDMARD due to either lack of efficacy (after ≥ 12 weeks at
                  an adequate dose) or intolerance (regardless of treatment duration).

          -  Must have a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 at
             the Screening and Baseline Visits.

          -  Must have a Total Back Pain score ≥ 4 based on a 0 - 10 numerical rating scale at the
             Screening and Baseline Visits.

          -  Has had an inadequate response to at least 2 nonsteroidal anti-inflammatory drugs
             (NSAIDs) over an at least 4-week period in total at maximum recommended or tolerated
             doses, or has an intolerance to or contraindication for NSAIDs as defined by the
             Investigator.

        Exclusion Criteria:

          -  Must not have been exposed to any Janus kinase (JAK) inhibitor (including but not
             limited to upadacitinib [Rinvoq®], tofacitinib [Xeljanz®], baricitinib [Olumiant®],
             filgotinib, ruxolitinib [Jakafi®], abrocitinib [PF-04965842], and peficitinib
             [Smyraf®]).

          -  Prior bDMARD therapy must be washed out.

          -  Participant must not have a history of an allergic reaction or significant sensitivity
             to constituents of the study drug.