5.1 INCLUSION CRITERIA
Potential participants are eligible to be included in the study only if all of the following criteria apply: 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 of childbearing 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." Conventional Therapy Failure
– Steroids (e.g., systemic prednisone, oral budesonide) The following definitions will be used as guidelines for the use of corticosteroids in this trial:
o Corticosteroid refractory: Persistent active disease despite treatment with at least one 4-week induction regimen, including a starting dose of ≥ 20 mg of oral prednisone (or equivalent) for at least 2 weeks or IV prednisone for ≥ 5 days, or persistently active disease after at least 4 weeks of oral budesonide given 9 mg/day
o Corticosteroid dependent: At least two failed attempts to taper corticosteroids below 10 mg oral prednisone daily (or its equivalent) or inability to taper oral budesonide to 6 mg/day or below without active disease
o Corticosteroid intolerant: History of intolerance to corticosteroids (including but not limited to Cushing syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, infection)
– At least 12 weeks of an immunomodulator, which can include:
o ≥ 1.5 mg/kg/day of oral azathioprine (AZA) (or per local standard of care)
o ≥ 0.75 mg/kg/day of 6-mercaptopurine (6-MP)
o ≥15 mg/week of intramuscular or SC methotrexate (MTX)
o Persistent signs and symptoms of active disease despite a 6-TG level of ≥230 pmol/8≥108 RBCs during at least one 12-week regimen of oral AZA or 6-MP at a stable or increasing dose. o History of intolerance to AZA, 6-MP, or MTX (including, but not limited to, nausea/vomiting, abdominal pain, pancreatitis, LFT abnormalities, lymphopenia, TPMT genetic mutation, infection).
– At least 4 weeks of an oral aminosalicylates, which can include a minimum dose of the following:
o 2.4 g/day of mesalamine
o 4.0 g/day of sulfasalazine
o 1.0 g/day of olsalazine
o 6.75 g/day of balsalazide
– The conventional therapy failure population will also include patients who have received advanced therapy (biologics or small molecules) in the past but stopped therapy based on reasons other than failure (e.g., change in reimbursement coverage, well-controlled disease). Advanced Therapy Failure – Anti-TNF agents, including and not limited to the following:
o At least one 6-week induction regimen of infliximab (≥5 mg/kg IV at 0, 2, and 6 weeks or per local label) or equivalent biosimilar
o At least one 8-week induction regimen of adalimumab (one 160 mg SC dose followed by one 80 mg SC dose [or one 80 mg SC dose in countries where this dosing regimen is allowed] followed by one 40 mg SC dose at least 2 weeks apart or per local label) or equivalent biosimilar
o At least one 2-week induction regimen of golimumab (one 200 mg SC dose followed by one 100 mg SC dose at least 2 weeks apart or per local label) – Anti-integrins, including and not limited to the following:
o At least one 6-week induction regimen of vedolizumab (300 mg IV at 0, 2, and 6 weeks or per local label) – Anti-IL12/IL23, including and not limited to the following:
o At least one 8-week induction regimen of ustekinumab (a single IV dose using weight-based dosing (260 mg for participants with body >55 kg; 390 mg for participants with body weight ≥55 kg to ≤85 kg; 520 mg for participants with body weight 85 kg or per local label) (single weight-based dose) or equivalent biosimilar
o At least one 8-week regimen of mirikizumab (300 mg IV at Weeks 0, 4, and 8 or per local label)
– JAK inhibitors, including and not limited to the following:
o At least one 8-week induction course of upadacitinib (45 mg orally daily or per local label) o At least one 8-week induction course of tofacitinib (10 mg orally twice daily of the immediate-release tablet or 22 mg orally daily of the extended-release tablet or per local label) – S1P receptor modulators, including and not limited to the following: o At least one 10-week induction course of ozanimod (0.92 mg orally daily)
o At least one 12-week induction course of etrasimod (2 mg orally daily)

5.2 EXCLUSION CRITERIA
Potential participants are excluded from the study if any of the following criteria apply:
Inflammatory Bowel Disease Exclusion Criteria
- Severe UC as evidenced by any of the following:
– Hospitalization for the treatment of UC ≤ 4 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 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  upper limit of normal (ULN), total bilirubin  2  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  109/L (1500/L) with one exception:
Participants with benign ethnic neutropenia (BEN): ANC  1.3  109/L (1300/L)
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/L
- Hemoglobin  8 g/dL
- Absolute lymphocyte count  500/L
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-aminosalicyclic 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

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