This study is comparing 200 milligrams (mg) of filgotinib a day with a placebo to see if filgotinib helps to treat Axial Spondyloarthritis (axSpA) and is safe to use. The study will also be comparing 200 mg with 100 mg filgotinib a day to see if the lower dose also helps to treat axSpA.

Key Inclusion Criteria:

• Have an established diagnosis of axSpA by a rheumatologist (or other specialist with expertise in diagnosing axSpA).

• Study A (r-axSpA): Meet Assessment of SpondyloArthritis International Society (ASAS) classification criteria with radiographic sacroiliitis on X-ray as follows:

  1. History of back pain >=12 weeks and age at onset of back pain <45 years, AND
  2. Have radiographic bilateral grade 2-4 sacroiliitis or unilateral grade 3-4 sacroiliitis, based on New York grading system, confirmed by central reading, AND,
  3. >=1 spondyloarthritis (SpA) feature.

• Study B (nr- axSpA): Meet ASAS classification criteria without radiographic sacroiliitis on X-ray as follows:

  1. History of back pain >= 12 weeks and age at onset of back pain <45 years, AND
  2. No radiographic bilateral grade 2-4 sacroiliitis or unilateral grade 3-4 sacroiliitis, AND,
  3. Presence of sacroiliitis on MRI (based on central reading) and at least 1 SpA feature or when positive for human leukocyte antigen (HLA)-B27: having at least 2 SpA features, AND
  4. Have objective signs of inflammation, by sacroiliitis on MRI or elevated CRP.

• Have active axSpA at screening and Day 1 defined by:

  • Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >=4 (numeric rating scale [NRS] 0-10), AND
  • Spinal pain score >=4 (0-10 NRS) (based on BASDAI question 2),

• Have a history of inadequate response to >=2 NSAIDs at the maximum dose of NSAIDs used in axSpA for >=2 weeks each (a total duration of NSAID trial >=4 weeks) or intolerance to >=2 NSAIDs for the treatment of axSpA.

• Participants who are biologic disease-modifying antirheumatic drug (BDMARD)(s) experienced; defined as below.

  • Participants designated as bDMARD(s)-inadequate responder(IR) must have received not more than 2 bDMARD(s), that was/were administered in accordance with its/their labeling and discontinued due to:

    • Non-response (primary or secondary) after a minimum treatment of 12 weeks, and /or
    • Intolerance (defined as having experienced an adverse reaction [e.g. an infusion/injection reaction, an infection, a laboratory test change, etc] irrespective of treatment duration)

  • Participants designated as bDMARD(s) non-IR have previously received bDMARD(s) and have discontinued these due to other reasons than non-response or intolerance (e.g. economic reasons, treatment as part of a clinical study, other, or unknown).

• If continuing conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during the study, participants are permitted to use only a maximum of 2 csDMARDs and must have been on this treatment for >=12 weeks prior to screening, with a stable dose and route of administration (defined as no change in prescription) for >4 weeks prior to Day 1.

• For participants aged 65 years or above on the date of signing the informed consent form (ICF), the investigator should carefully consider if participation is in the best interest of the participant.

Key Exclusion Criteria:

• Prior exposure to a Janus kinase inhibitor, investigational or approved, at any time, including filgotinib.
• Use of any opioid analgesic at average daily doses >30 mg/day of morphine (or equivalent) or use of unstable doses of any opioid analgesic <=2 weeks prior to Day 1.
• Use of any of the following systemic immunomodulating therapies <= 4 weeks prior to Day 1, including, but not limited to: 6-mercaptopurine, azathioprine, cyclosporine or other calcineurin inhibitors (e.g. sirolimus, tacrolimus), methotrexate if being discontinued, mycophenolate, antimalarials (e.g. hydroxychloroquine, chloroquine) if being discontinued, or sulfasalazine if being discontinued.
• Complete spinal ankylosis defined as the presence of consecutive bridging syndesmophytes in >=5 segments on the lateral radiograph (assessed by the central reader).
• Have undergone surgical treatments for peripheral manifestation of axSpA, including synovectomy or arthroplasty, or major surgery (requiring regional block or general anesthesia) <=12 weeks prior to Day 1 or planned major surgery during the study.
• Have a diagnosis of any generalized musculoskeletal disorder, e.g. generalized osteoarthritis, or systemic inflammatory condition other than axSpA.
• Have active Crohn's disease (CD) or active ulcerative colitis (UC). Note: participants may be enrolled if they have had a history of inflammatory bowel disease (IBD), including CD and UC, but have had no exacerbation within 6 months prior to Day 1, and, if currently on treatment, must be on stable treatment for >=6 months prior to Day 1 and this treatment should be allowed per protocol.
• Active autoimmune disease that would interfere with assessment of study parameters or increase risk to the participant by participating in the study (e.g. uncontrolled uveitis, uncontrolled thyroiditis, transverse myelitis, current peptic ulcer disease or prior history of severe diverticulitis [i.e. requiring hospitalization] or previous gastrointestinal perforation), per judgment of investigator,
• History of opportunistic infection, or immunodeficiency syndrome, which would put the participant at risk, as per investigator judgment,
• Active infection that is clinically significant, as per judgment of the investigator, or history of a serious infection (requiring hospitalization or systemic antibiotics) within 12 weeks prior to screening.
• Participant has a history of malignancy or myelo- or lymphoproliferative disorder, including non-melanoma skin cancer (NMSC), excised and curatively treated non-metastatic basal cell carcinoma, squamous cell carcinoma of the skin, or in situ uterine cervical carcinoma within the past 5 years prior to screening.
• Participant has any other condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g. compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. For participants at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past (>10 pack-years) and those at increased risk of cancer, the investigator should carefully consider if participation is in the best interest of the participant.
• Contraindication to magnetic resonance imaging (MRI).