Evaluation of Guselkumab Subcutaneous Induction Therapy Efficacy and Safety in Moderate to Severe Ulcerative Colitis: A Phase 3 Randomized, Double-blind, Placebo-controlled Study

The primary objective of this Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study is to evaluate the **efficacy**, including clinical remission, of **guselkumab** subcutaneous induction therapy compared to placebo in participants with moderately to severely active **ulcerative colitis**. This objective is clinically relevant as it aims to determine the potential of guselkumab to induce remission in a population with significant disease activity, thereby potentially offering a new therapeutic option for managing this chronic inflammatory condition.

The clinical trial involves a total of **174 participants** diagnosed with **moderate to severely active ulcerative colitis**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on a documented diagnosis of ulcerative colitis for at least three months prior to baseline, and they exhibit moderately to severely active disease as assessed by the modified Mayo score. Additionally, participants have demonstrated an inadequate response to or intolerance of conventional therapies such as 6-mercaptopurine, azathioprine, or corticosteroids, as well as advanced therapies including TNFα antagonists, vedolizumab, ozanimod, or approved JAK inhibitors. The trial population includes individuals from a vulnerable population, although specific lifestyle considerations such as diet or physical activity are not detailed in the available data.

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled, parallel-group, multicenter study designed to evaluate the efficacy and safety of **guselkumab** subcutaneous induction therapy in participants with moderately to severely active **ulcerative colitis**. The trial aims to assess the clinical remission of the condition at week 12, comparing the effects of guselkumab to a placebo. The study is expected to run until December 31, 2028, with recruitment starting on October 13, 2023. Participants will be involved in the study for a maximum treatment period of 248 weeks.

The trial will include several study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a documented diagnosis of ulcerative colitis for at least three months prior to baseline and a demonstrated inadequate response to or intolerance of conventional or advanced therapy. Following the screening, participants will undergo randomization to receive either guselkumab or a placebo. The study will involve regular follow-up visits to monitor the participants' health and response to the treatment, ensuring adherence to the protocol and assessing any adverse events. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the primary and secondary endpoints.

Participants are expected to remain in the study for the entire duration unless specific conditions necessitate early termination. Such conditions may include significant adverse reactions, withdrawal of consent, or any other medical reasons deemed necessary by the investigator. The trial will utilize a solution for injection in pre-filled syringes, administered subcutaneously, with the use of devices such as the 2 mL YpsoMate autoinjector and the 1 mL UltraSafe Plus™ Passive Needle Guard to facilitate self-injection and ensure proper delivery of the medication.

The clinical trial involves the administration of **Guselkumab**, a monoclonal antibody, as the experimental medication. Guselkumab is provided in the form of a **solution for injection in a pre-filled syringe**. The pharmaceutical form is specifically designed for **subcutaneous use**. The dosing regimen involves the administration of Guselkumab at a concentration of 100 mg/mL. The maximum treatment period for this medication is 248 days. The administration device used is the 2 mL YpsoMate autoinjector, which ensures automatic dose delivery following manual activation. This device houses a pre-filled syringe with a permanently bonded ½" long needle. An alternative device, the 1 mL UltraSafe Plus™ Passive Needle Guard, is also utilized, facilitating self-injection and enabling passive activation of a needle guard post-delivery.

In addition to the experimental treatment, the study includes the use of a placebo, referred to as Guselkumab 1 mL PFS Placebo and Guselkumab 2 mL PFS Placebo. These placebo formulations are designed to match the experimental medication in appearance and administration method but do not contain the active substance. The placebo is used to maintain the double-blind nature of the study, ensuring unbiased 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 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. The primary endpoint for evaluating efficacy is clinical remission at week 12. This endpoint will be measured using the modified Mayo score, which is a validated scale commonly used to assess disease activity in ulcerative colitis. Participants will be evaluated for clinical remission, which is defined as a specific score on the modified Mayo scale, indicating a significant reduction in disease activity.