Efficacy and Safety Evaluation of Guselkumab in Patients with Moderately to Severely Active Ulcerative Colitis: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** and **safety** of guselkumab in participants with moderately to severely active **ulcerative colitis**. This is clinically relevant as ulcerative colitis is a chronic inflammatory bowel disease that significantly impacts patients' quality of life, and effective treatment options are essential for managing symptoms and inducing remission.

The clinical trial involves a total of **1011 participants** diagnosed with **moderately to severely active ulcerative colitis**. The study population includes both male and female subjects, aged 18 years and older, who have a documented diagnosis of ulcerative colitis for at least three months prior to screening. Participants were selected based on their history of inadequate response to or failure to tolerate conventional or advanced therapy, as defined in the protocol. The trial population was chosen to ensure that screening laboratory test results fall within the study protocol's defined parameters. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, although specific details about this group are not provided. The selection criteria ensure a focus on individuals with a baseline modified Mayo score indicating moderate to severe disease activity.

The clinical trial is designed to evaluate the **efficacy** and safety of **guselkumab** in participants with moderately to severely active **ulcerative colitis**. This is a Phase 2b/3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. The trial will span an estimated duration from September 30, 2019, to December 9, 2027. Participants will be randomly assigned to receive either guselkumab or a placebo, administered via subcutaneous injection. The primary endpoint is the clinical response at induction week 12.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, documented diagnosis of ulcerative colitis, and history of inadequate response to previous therapies. Following successful screening, participants will be enrolled and randomized into the study. The trial includes multiple follow-up visits to monitor the participants' response to the treatment and to assess safety parameters. The end-of-study visit will conclude the trial for each participant, where final assessments will be conducted.

The expected length of participant involvement is up to 12 weeks, corresponding to the primary endpoint assessment at induction week 12. Conditions that may lead to early termination from the study include adverse events, withdrawal of consent, or any protocol violations that compromise the integrity of the trial. The study is not categorized as low intervention, and it involves the use of a monoclonal antibody as the investigational product. Participants will be closely monitored throughout the trial to ensure adherence to the protocol and to safeguard their well-being.

The clinical trial involves the administration of **Guselkumab**, a monoclonal antibody, as the experimental medication. Guselkumab is provided as a solution for injection in a pre-filled syringe, with a concentration of 100 mg/mL. The pharmaceutical form is designated as injection/infusion, and the route of administration is subcutaneous use. The dosing schedule involves administration over a maximum treatment period of 12 months. The pre-filled syringe is equipped with a 1 mL UltraSafe Plus™ Passive Needle Guard, which facilitates self-injection and ensures passive activation of the needle guard post-delivery. The active substance, guselkumab, is a protein of other origin, and the product is manufactured by Janssen-Cilag International N.V.

In addition to the experimental treatment, a placebo is utilized in the study. The placebo is labeled as Guselkumab 1 mL PFS Placebo and is administered in a similar manner to the active treatment, ensuring blinding in the double-blind, placebo-controlled trial design. The placebo is also delivered via subcutaneous injection, maintaining consistency in the administration route and form with the active treatment. The use of a placebo allows for the assessment of the efficacy and safety of guselkumab in participants with moderately to severely active ulcerative colitis.

The efficacy of guselkumab in the treatment of moderately to severely active **Ulcerative Colitis** will be assessed in a Phase 2b/3, randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial. The primary endpoint for evaluating efficacy is the Clinical Response at Induction Week 12. This endpoint will be measured using a baseline modified Mayo score, which is a validated scale commonly used to assess disease activity in ulcerative colitis. The trial will involve the administration of guselkumab as a solution for injection in a pre-filled syringe, with a dosage of 100 mg/mL, and will utilize the UltraSafe Plus™ Passive Needle Guard to facilitate self-injection. The trial is designed to ensure rigorous assessment of the therapeutic effects of guselkumab over a maximum treatment period of 12 weeks. Data collection and analysis will be conducted in accordance with the study protocol to ensure the reliability and validity of the efficacy outcomes.