General Inclusion Criteria:

• Signed Informed Consent Form – Signed Assent Form, when appropriate, as determined by the potential participant's age and individual site and country standards.
• Age ≥ 18 to ≤ 80 years at the time of signing Informed Consent Form Patients aged ≥ 16 to < 18 years may be eligible to participate in the study where locally permissible (e.g., if permitted by local guidelines and regulations).
• Bodyweight ≥ 40 kg.

Ulcerative Colitis-Specific Inclusion Criteria

• Confirmed diagnosis of UC with supportive clinical, endoscopic, and histopathological evidence .
• Active UC confirmed by endoscopy (flexible sigmoidoscopy or colonoscopy) extending ≥15 cm from the anal verge Participants with proctitis only at baseline will be capped at 10% of the total enrollment.
• Moderately to severely active UC, defined as an mMS of 5 to 9 points, including a Mayo endoscopic score (ES) of 2 or 3, confirmed through centrally-read endoscopy performed either:
  • During the screening period
  • Before the screening period (independently of the study), within 2 weeks of screening, and in patients who already have an established UC diagnosis.
  • If performed before screening, the endoscopy must have a video recording available and in a format that is suitable for central reading. Use of previous endoscopies for screening is only permitted if performed according to the endoscopy procedural manual/charter specifications.
• Receipt of a surveillance colonoscopy (performed according to local standards) within the 2 years prior to baseline to rule out dysplasia in participants with pancolitis > 8 years duration and participants with left-sided colitis > 12 years duration. Participants without a surveillance colonoscopy within the prior 2 years must be willing to have a colonoscopy at screening (i.e., in place of screening flexible sigmoidoscopy). Any adenomatous polyps must be removed according to routine practice prior to their first dose of study drug.

Reproductive Inclusion Criteria

• For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for 95 days after the final dose of RO7790121 A female participant is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (  ≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a female participant with a tubal ligation is considered to be of childbearing potential. The definition ofchildbearing potential may be adapted for alignment with local guidelines or regulations. The following are examples of adequate contraceptive methods: bilateral tubal ligation; male sterilization; hormonal contraceptives; hormone-releasing intrauterine devices; copper intrauterine devices; male or female condom with or without spermicide; and cap, diaphragm, or sponge with spermicide. A male condom and a female condom should not be used together because of risk of failure due to friction. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.
• For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm, as defined below: With a female partner of childbearing potential or pregnant female partner, male participants must remain abstinent or use a condom during the treatment period and for 95 days after the final dose of RO7790121 to avoid exposing the embryo. Male participants must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure. If required per local guidelines or regulations, information about the reliability of abstinence will be described in the local Informed Consent Form.

Prior Medications Inclusion Criteria

• Must have had at least one of the following treatments in the past with inadequate response, loss of response, and/or intolerance Inadequate response is defined as having signs and symptoms of persistently active disease despite completing at least the approved dosing regimen in the product label. Intolerance may include, but is not limited to, infusion-related reactions, injection site reactions, rash, serum sickness, hepatic abnormalities, demyelination, congestive heart failure, and infections. There is no minimum requirement for dose or duration if a potential participant was determined to be intolerant to prior treatment. Loss of response is defined as the recurrence of signs and symptoms of active disease during approved treatment following prior clinical benefit (discontinuation despite clinical benefit does not qualify as having failed or being intolerant to UC Advanced therapy). The medication used to qualify the participant for entry into this category must be approved for the treatment of UC, including biosimilars. Participants previously exposed to investigational therapies for the treatment of UC must still meet inclusion criteria "Conventional Therapy Failure” or “Advanced Therapy Failure".

Exclusion Criteria:

Inflammatory Bowel Disease Exclusion Criteria

• Severe UC as evidenced by any of the following:
  • Hospitalization for the treatment of UC 2 weeks prior to screening or, in the physician's judgement, is likely to require hospitalization for medical care or surgical intervention of any kind for UC (e.g., colectomy) during the study.
  • Current evidence of fulminant colitis, toxic megacolon, or recent history (within 6 months) of toxic megacolon, or bowel perforation.
  • Prior extensive colonic resection, subtotal, or total colectomy, or planned surgery for UC during the study.
• Current diagnosis of Crohn's disease (CD), abdominal/intrabdominal/perianal fistula and/or abscess, indeterminant colitis, IBD-unclassified, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, or active diverticular disease.
• Presence of an ostomy or ileoanal pouch.
• Current diagnosis or suspicion of primary sclerosing cholangitis.

Medical History Exclusion Criteria

• Lack of peripheral venous access.
• Any major surgery within 6 weeks prior to screening or a major surgery planned during the study.
• Any serious, chronic and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with the potential participant's safety, provision of informed consent, or compliance with trial procedures.
  • Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 95 days after the final dose of RO7790121 Female participants of childbearing potential must have a negative serum pregnancy test result at screening and a negative urine pregnancy test on Day 1 prior to initiation of study treatment.
• Any condition that would preclude endoscopic evaluation.
• Past or current evidence of definite low-grade or high-grade colonic dysplasia or adenomas or neoplasia not completely removed.
• History of malignancy within 5 years prior to screening visit, with the exception of malignancies adequately treated with resection for non-metastatic basal cell or squamous cell cancer or in situ cervical cancer.
• History of alcohol, drug, or chemical abuse < 1 year prior to screening.

Infection or Infection Risk Exclusion Criteria

• Any clinically significant infection 3 months prior to randomization that required hospitalization, IV antibiotics, did not resolve, or was opportunistic in nature.
• Evidence of or treatment for Clostridioides difficile (C. difficile; formerly known as Clostridium difficile) as assessed by C. difficile toxin testing) within 60 days prior to randomization (Day 1) or other enteric pathogens (as assessed by stool culture and ova and parasite evaluation) within 30 days prior to randomization (Day 1).
• Any diagnosis of cytomegalovirus (CMV) colitis in the past 60 days (including diagnosis during screening) – Laboratory confirmation of CMV from a colon biopsy sample is required during screening evaluation only if clinical suspicion is high and to determine the need for CMV treatment.
• Positive HIV test at screening.
• Positive test results for hepatitis B infection at screening, defined as meeting either of the following criteria: – Positive hepatitis B surface antigen (HbsAg) test at screening – Quantitative HBV DNA above the lower limit of quantification in patients with a negative hepatitis B surface antibody (HbsAb) test and positive total hepatitis B core antibody (HbcAb) test.
• Positive hepatitis C virus (HCV) antibody test at screening.
• Positive for tuberculosis (TB) during screening or within 3 months prior to screening, defined as a positive QuantiFERON-TB Gold test® (QFT) or, if QFT is not available, a positive purified protein derivative (PPD) skin test according to local guidelines or regulations or other locally approved TB enzyme-linked immunosorbent assay (ELISA) tests (e.g., T-SPOT® ), with the following exceptions: – Potential participants with a history of Bacillus Calmette-Guérin (BCG) vaccination who have a positive PPD skin test will not be excluded if they have a negative QFT at screening. – Potential participants who have a positive or indeterminate QFT and those with no history of BCG vaccination who have a positive PPD skin test will not be excluded if they meet all of the following criteria: o No symptoms that are consistent with TB o Documented history of a completed course of adequate prophylaxis (completed treated for latent TB) per local standard of care prior to randomization (Day 1). o No known exposure to a case of active TB after most recent prophylaxis. o No evidence of active TB on chest X-ray performed during screening or within 3 months prior to screening.
• History of organ transplant.
• Acquired or congenital immunodeficiency.

Laboratory Results Exclusion Criteria

• Clinically significant abnormality on laboratory tests during screening (hematology, serum chemistry, and urinalysis) that, in the opinion of the investigator, may pose an additional risk in administering study treatment to the potential participant.
• ALT, AST, or ALP  ≥ 2.5 x upper limit of normal (ULN), total bilirubin  ≥ 2 x ULN, or presence of abnormalities in synthetic liver function tests judged to be clinically significant by the investigator. Patients with known Gilbert syndrome who have unconjugated hyperbilirubinemia will not be excluded. ANC <  1.5 x 109 /L (1500/uL) with one exception: Participants with benign ethnic neutropenia (BEN): ANC < 1.3 x 109 /L (1300/uL) BEN (also known as constitutional neutropenia) is an inherited cause of mild or moderate neutropenia that is not associated with any increased risk for infections or other clinical manifestations (Atallah-Yunes et al. 2019). BEN is referred to as ethnic neutropenia because of its increased prevalence in people of African descent and other specific ethnic groups.
• Platelet count < 100,000/uL.
• Hemoglobin < 8 g/dL.
• Absolute lymphocyte count < 500/uL.

Prohibited Medications Exclusion Criteria

• Any of the following related to previous or current treatment:
  • Use of approved UC treatments including approved oral small molecule (e.g., S1P receptor modulator, JAK inhibitor) treatments within 2 weeks, or approved biologic agents within 8 weeks or 5 half-lives, whichever is longer.
  • If there is proper documentation of undetectable drug level measured by a commercially available assay for any of the approved biologics, there is no minimum washout prior to screening.
  • Use of any investigational or experimental therapy within approximately 30 days for non-biologic therapy or 8 weeks for biologic therapy OR 5 half-lives (whichever is longer) prior to randomization (Day 1.
  • Treatment with IV corticosteroids ≤ 2 weeks prior to screening or during the study.
  • Presence of conditions other than UC (e.g., uncontrolled asthma) that could require treatment with > 20 mg/day of prednisone (or equivalent) during the course of the study.
  • Treatment with corticosteroid enemas or suppositories and/or topical (rectal) 5-aminosalicylic acid (5-ASA) preparations ≤  2 weeks prior to screening or during the study.
  • Treatment with topical rectal traditional medicine (e.g., Chinese medicine), herbal enemas, or suppositories ≤ 2 weeks prior to screening or during the study.
  • Transplant/stem cell therapy at any time prior to or during the study.
  • Treatment ≤ 16 weeks prior to or during screening with cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil.
  • Apheresis ≤ 2 weeks prior to screening or intent to receive during the study.
  • Receipt of fecal microbial transplantation within 4 weeks prior to randomization (Day 1)
  • Known exposure to anti-TL1A (RO7790121 [RVT-3101]/PF-06480605) or any type of anti-TL1A therapy.
  • Receipt of a live or attenuated vaccine ≤ 4 weeks prior to screening; use of non-live (inactivated) vaccines are allowed.
  • Chronic (e.g. >7 days) nonsteroidal anti-inflammatory drug (NSAID) use; occasional use of NSAIDs and acetaminophen (e.g., headache, arthritis, myalgias, or menstrual cramps) and aspirin  ≤ 325 mg/day is permitted.
  • Treatment with immunoglobulin or blood products within 4 weeks prior to screening, or any condition that is likely to require such treatment during the course of the study.
  • Previous severe allergic reaction or anaphylactic reaction to biologic agents or to any excipients of the study drug.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 8/07/2024. Questions regarding updates should be directed to the study team contact.