Study Purpose: This is a multicenter, randomized, placebo controlled study to evaluate the efficacy and safety of investigational ABX464 given at 25 or 50 mg QD in inducing clinical remission in subjects with moderately to severely active ulcerative colitis who have inadequate response, no response, a loss of response, or an intolerance to either conventional therapies [corticosteroids, immunosuppressant (i.e. azathioprine, 6-mercaptopurine, methotrexate)] and/or advanced therapies [biologics (TNF inhibitors, anti-integrins, anti-IL-23), and/or S1P receptor modulators, and/or JAK inhibitors].

To be enrolled in this study, you must meet certain requirements. You may be eligible to participate if you meet the following criteria:

Study Duration: 8 WEEKS

Study Commitment: To compare the efficacy of ABX464 versus placebo on clinical remission

Age: Over 16 years old

Sex: Male & Female

Conditions/Eligibility: Men or women at least 16 years old; Adolescent subjects will only be enrolled if approved by the country regulatory/health authority. If these approvals have not been granted, only subjects ≥ 18 years old will be enrolled. To be eligible, adolescent subjects must weigh ≥ 40 kg and meet the definition of Tanner Stage 5 at the screening visit. Subjects must understand, sign and date the written voluntary informed consent form at the visit prior to any protocol-specific procedures. For under-aged subjects, national requirements regarding consent should also be met. Documented diagnosis of UC confirmed by endoscopy and histology. Should endoscopy/histology results not be available at screening, results from endoscopies and biopsies taken at screening may be used. Active disease defined by modified Mayo score (MMS) ≥ 5 with rectal bleeding subscore (RBS) ≥ 1 and endoscopy subscore (MES) of 2 or 3 (confirmed by central reader). Subjects with documented inadequate response (defined as lack of response or loss of response or intolerance) to at least one of the following treatments: corticosteroids, immunosuppressant, biologic or biosimilar therapies, S1P receptor modulators and/or JAK inhibitors and/or new drugs approved during the study (note: failure to only 5-ASA or sulfasalazine is not accepted). Women of childbearing potential (WOCBP) subjects and male subjects with WOCBP partner must agree to comply with the contraception requirements described in the protocol. Subjects able and willing to comply with study visits and procedures as per protocol. Subjects should be affiliated to a health insurance policy whenever required by a participating country or state.

Study Procedures: Colonoscopy or sigmoidoscopy, IV infusion, SC injection

Compensation: $53 per on-site visit, additional $25 meal stipend for patient and 1 companion