Study to Evaluate the Efficacy and Safety of Tilpisertib in Adults With Moderately to Severely Active Ulcerative Colitis

Key Inclusion Criteria:

• Males, or non-pregnant, non-lactating females, at least 18 years of age based on thedate of the screening visit.
• UC of at least 3 months duration before randomization confirmed by endoscopy andhistology at any time in the past AND a minimum disease extent of 15 centimeter (cm)from the anal verge. Documentation of endoscopy and histology consistent with thediagnosis of UC must be available in the source documents prior to the initiation ofscreening.
• Moderately to severely active UC as determined during screening by a centrally readendoscopy score ≥ 2, a Rectal Bleeding subscore ≥ 1, a Stool Frequency subscore ≥ 1and Physicians Global Assessment (PGA) of ≥ 2 as defined by the Mayo Clinic Score;total MCS must be between 6 and 12, inclusive.
• Previously demonstrated an inadequate response (primary non-response) or loss ofresponse (secondary non-response) to a tumor necrosis factor-alpha (TNFα) inhibitor (ie, infliximab, adalimumab, golimumab, or biosimilars). The induction treatmentregimen resulting in inadequate response or loss of response should have been inaccordance with local prescribing information/guidelines or as outlined below.
• Infliximab: 5 mg/kg at Weeks 0, 2, and 6
• Adalimumab: 160 mg on Day 1 (given in 1 day or split over consecutive days),followed by 80 mg 2 weeks later (Day 15), 40 mg 2 weeks later (Day 29) and every 2 weeks thereafter until Day 57
• Golimumab: 200 mg on Day 1 followed by 100 mg at Week 2
• May be receiving concomitant therapy for UC at the time of enrollment as specified inthe protocol, provided the dose prescribed has been stable as indicated prior torandomization.
• Meet the following Tuberculosis (TB) screening criteria:
• No evidence of active TB, latent TB, or inadequately treated TB as evidenced by 1of the following:
• A negative QuantiFERON test or equivalent assay reported by the central labat screening or within 90 days prior to randomization date. OR
• A history of fully treated active or latent TB according to local standardof care. Investigator must verify adequate previous anti-TB treatment andprovide documentation; these individuals do not require QuantiFERON testingand eligibility must be approved by the sponsor prior to enrollment in thestudy. AND
• A chest radiograph (views as per local guidelines with the report or filmsavailable for investigator review) taken at screening or within the 4 monthsprior to randomization without evidence of active or latent TB infection.
• Laboratory assessments at screening within the following parameters:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and totalbilirubin ≤ 2 X upper limit of normal (ULN)
• Estimated glomerular filtration rate (eGFR) ≥ 60 ml/min (1.0 mL/sec) ascalculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)Cystatin C formula as described in protocol.
• Hemoglobin ≥ 8 g/dL (≥ 80 g/L)
• Absolute neutrophil count (ANC) ≥ 1.5 × 10^3/μL (≥ 1.5 GI/L)
• Platelets ≥ 100 × 10^3/μL (≥ 100 GI/L)
• White blood cells (WBC) ≥ 3 × 10^3/μL (≥ 3 GI/L)
• Absolute lymphocyte count ≥ 0.75 × 10^3/μL (≥ 0.75 GI/L)

Key Exclusion Criteria:

• Currently displaying clinical signs of acute severe colitis, fulminant colitis, ortoxic megacolon. Note: Other protocol defined Inclusion/Exclusion criteria may apply.