A Study Evaluating the Safety and Efficacy of Upadacitinib in Adults With Active Ankylosing Spondylitis
Condition: Ankylosing Spondylitis (AS)
MeSH terms: Spondylitis; Spondylarthritis; Spondylitis, Ankylosing
Intervention: Upadacitinib; Placebo
Intervention description: Tablet; Tablet
Intervention MeSH terms: Upadacitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 187.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Upadacitinib; ABT-494; Ankylosing Spondylitis (AS); Safety; Efficacy

Summary:

      The purpose of this study is to evaluate the safety and efficacy of upadacitinib in
      participants with active ankylosing spondylitis (AS) who have had an inadequate response to
      at least 2 non-steroidal anti-inflammatory drugs (NSAIDs) or intolerance to or a
      contraindication for NSAIDs, and who are naïve to biologic disease-modifying anti-rheumatic
      drugs (bDMARD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant with a clinical diagnosis of ankylosing spondylitis (AS) and meeting the
             modified New York criteria for AS.

          -  Participant must have baseline disease activity as defined by having a Bath Ankylosing
             Spondylitis Disease Activity Index (BASDAI) score >= 4 and a Patient's Assessment of
             Total Back Pain score >= 4 based on a 0 - 10 numeric rating scale (NRS) at the
             Screening and Baseline visits.

          -  Participant has had an inadequate response to at least two nonsteroidal
             anti-inflammatory drugs (NSAIDs) over an at least 4-week period in total at maximum
             recommended or tolerated doses, or participant has an intolerance to or
             contraindication for NSAIDs as defined by the Investigator.

          -  If entering the study on concomitant methotrexate (MTX), leflunomide, sulfasalazine
             (SSZ), and/or hydroxychloroquine, participant must be on a stable dose of MTX (<= 25
             mg/week) and/or SSZ (<= 3 g/day) and/or hydroxychloroquine (<= 400 mg/day) or
             leflunomide (<= 20 mg/day) for at least 28 days prior to the Baseline visit. A
             combination of up to two background conventional synthetic disease-modifying
             anti-rheumatic drugs (csDMARDs) is allowed except the combination of MTX and
             leflunomide.

          -  If entering the study on concomitant oral corticosteroids, participant must be on a
             stable dose of prednisone (<= 10 mg/day), or oral corticosteroid equivalents, for at
             least 14 days prior to the Baseline visit.

          -  If entering the study on concomitant NSAIDs, tramadol, combination of acetaminophen
             and codeine or hydrocodone, and/or non-opioid analgesics, participant must be on
             stable dose(s) for at least 14 days prior to the Baseline visit.

        Exclusion Criteria:

          -  Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to
             tofacitinib, baricitinib, and filgotinib).

          -  Prior exposure to any biologic therapy with a potential therapeutic impact on
             spondyloarthritis (SpA).

          -  Intra-articular joint injections, spinal/paraspinal injection(s), or parenteral
             administration of corticosteroids within 28 days prior to the Baseline visit. Inhaled
             or topical corticosteroids are allowed.

          -  Participant on any other DMARDs (other than those allowed), thalidomide or apremilast
             within 28 days or five half-lives (whichever is longer) of the drug prior to the
             Baseline visit.

          -  Participant on opioid analgesics (except for combination acetaminophen/codeine or
             acetaminophen/hydrocodone which are allowed) or use of inhaled marijuana within 14
             days prior to the Baseline visit.

          -  Participant has a history of inflammatory arthritis of different etiology other than
             axial SpA (including but not limited to rheumatoid arthritis, psoriatic arthritis,
             mixed connective tissue disease, systemic lupus erythematosus, reactive arthritis,
             scleroderma, polymyositis, dermatomyositis, fibromyalgia), or any arthritis with onset
             prior to 17 years of age.

          -  Laboratory values meeting the following criteria within the Screening period prior to
             the first dose of study drug: serum aspartate transaminase > 2 × upper limit of normal
             (ULN); serum alanine transaminase > 2 × ULN; estimated glomerular filtration rate by
             simplified 4-variable Modification of Diet in Renal Disease formula < 40 milliliter
             (mL)/minute/1.73m^2; hemoglobin < 10 gram/deciliter, total white blood cell count <
             2,500/microliter (μL); absolute neutrophil count < 1,500/μL; absolute lymphocyte count
             < 800/μL; and platelet count < 100,000/μL.