Overview
The purpose of this protocol is to evaluate the efficacy and safety of tulisokibart in participants with moderately to severely active ulcerative colitis. Study 1's primary hypotheses are that at least 1 tulisokibart dose level is superior to Placebo in the proportion of participants achieving clinical remission per Modified Mayo Score at Week 12, and that at least 1 tulisokibart dose level is superior to Placebo in the proportion of participants achieving clinical remission per Modified Mayo Score at week 52. Study 2's primary hypothesis is that at least 1 tulisokibart dose level is superior to Placebo in the proportion of participants achieving clinical remission per Modified Mayo Score at Week 12.
Description
The protocol consists of 2 studies. Study 1 includes induction and maintenance treatment, and Study 2 includes only induction treatment. Each study has its own hypotheses and outcome measures that will be assessed independently.
Eligibility
Inclusion Criteria:
- Has had ulcerative colitis (UC) (from onset of symptoms) for at least 3 months before randomization
- Has moderately to severely active UC
- Weight ≥40 kg
- Satisfies at least 1 of the following criteria:
- Has had an inadequate response or loss of response to 1 or more protocol-specified UC treatments
- Protocol specified corticosteroid dependence
- Has been intolerant to 1 or more protocol-specified UC treatments
- Is on treatment with any protocol-specified drugs during the study and meets drug
stabilization requirements, as applicable
- Adolescent participants ≥16 and <18 years of age can participate if approved by the country or regulatory/health authority
- Participant assigned male sex at birth, if capable of producing sperm, agrees to abstain from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent; or uses prescribed contraception unless azoospermic
- A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding and Is not a participant of childbearing potential (POCBP); or is a POCBP and uses an acceptable contraceptive method, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention, medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy
Exclusion Criteria:
- Has a diagnosis of Crohn's Disease (CD) or indeterminate colitis (inflammatory bowel disease (IBD)-undefined) or other types of colitis or enteritis that may confound efficacy assessment.
- Has a current diagnosis of fulminant colitis and/or toxic megacolon
- Has UC limited to the rectum (i.e, must have evidence of UC extending beyond the rectosigmoid junction, which is ~10 cm from the anal margin)
- Has a current or impending need for colostomy or ileostomy
- Has had a total proctocolectomy or partial colectomy
- Has received fecal microbial transplantation within 4 weeks before randomization
- Has been hospitalized for the treatment of UC within 2 weeks before screening
- Has prior or current evidence of definite low-grade or high-grade colonic dysplasia including dysplasia identified during the Screening colonoscopy that has not been completely removed
- Has any active or serious infections without resolution after adequate treatment
- Has had a herpes zoster reactivation or cytomegalovirus that resolved less than 8 weeks before screening
- Has a transplanted organ which requires continued immunosuppression
- Has a history of cancer (except fully treated non-melanoma skin cell cancers or cervical carcinoma in situ after complete surgical removal) within the last 5 years
- Is known to be infected with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
- Has evidence of active tuberculosis (TB), latent TB not successfully treated (per local guidelines), or inadequately treated TB (for participants with history of TB)
- Has confirmed or suspected COVID-19 infection
- Has a history of drug or alcohol abuse within 6 months prior to screening
- Has had major surgery within 3 months before screening or has a major surgery (i.e, requiring general anesthesia) planned during the study
- Is currently receiving or is planning to receive total parenteral nutrition at any time during study treatment
- Has received UC-related antibiotics and has not been on stable doses for at least 14 days before randomization or has discontinued these medications within 14 days of randomization
- Requires treatment with a therapy that does not adhere to the protocol-specified guidance parameters
- Has received protocol-specified prohibited medications
- Has had prior exposure to tulisokibart or another anti-tumor necrosis factor-like cytokine 1A (TL1A) antibody