A Phase 3 Randomized, Open-label Induction, Double-blind Maintenance, Parallel-group, Multicenter Protocol to Evaluate the Efficacy, Safety, and Pharmacokinetics of Guselkumab in Pediatric Participants with Moderately to Severely Active Ulcerative Colitis

The primary objective of this study is to evaluate the **efficacy** of **guselkumab** in pediatric participants with moderately to severely active **ulcerative colitis** (UC) at the end of maintenance therapy among those who were induction responders. This is clinically relevant as it aims to determine the therapeutic potential of guselkumab in managing UC, a chronic inflammatory bowel disease, in a pediatric population, which could lead to improved treatment options and outcomes for this age group.

The clinical trial involves a total of **42 participants** diagnosed with **Ulcerative Colitis**. The study population comprises pediatric subjects aged **2 to less than 18 years**, inclusive, at the time of the first administration of the study intervention. Both **male and female** participants are included, and the trial specifically targets a vulnerable population. Participants were selected based on their diagnosis of moderately to severely active Ulcerative Colitis, with a baseline modified Mayo score ranging from 5 to 9, and a screening Mayo endoscopy subscore of at least 2. The trial includes individuals who have either failed advanced therapy or are naïve to such treatments, with a history of inadequate response or intolerance to standard therapies such as corticosteroids, aminosalicylates, or immunomodulators. The selection criteria ensure that participants have a documented history of the disease, supported by pathology reports or screening endoscopy with biopsies. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **efficacy**, safety, and pharmacokinetics of **guselkumab** in pediatric participants with moderately to severely active **ulcerative colitis**. This is a Phase 3, randomized, open-label induction, double-blind maintenance, parallel-group, multicenter study. The trial is expected to commence recruitment on March 29, 2024, and conclude by August 14, 2028. The study involves a series of visits, beginning with a screening visit to confirm eligibility based on specific inclusion criteria, such as age between 2 to less than 18 years and a documented diagnosis of ulcerative colitis. Participants will be randomly assigned to receive either guselkumab or a placebo, with the treatment administered via subcutaneous or intravenous routes, depending on the formulation.

The trial consists of an induction phase followed by a maintenance phase, with the primary endpoint being clinical remission at Week 56. Participants will attend regular follow-up visits to monitor their response to treatment and assess any adverse events. The end-of-study visit will evaluate the overall outcomes and gather final data. The expected duration of participant involvement is up to 56 weeks, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The study aims to provide comprehensive data on the therapeutic potential of guselkumab in managing pediatric ulcerative colitis, contributing to the understanding of its role in this patient population.

The clinical trial involves the administration of **Guselkumab**, a monoclonal antibody, in various pharmaceutical forms and dosages. The primary experimental medication is Guselkumab, provided as a **solution for injection in a pre-filled syringe**. This formulation is intended for **subcutaneous use**. The dosing schedule and frequency are determined based on the trial protocol, with a maximum treatment period of 56 weeks. The medication is manufactured by Janssen-Cilag International N.V. and is not a pediatric formulation. The administration of Guselkumab is facilitated by devices such as the 2mL UltraSafe Plus Passive Needle Guard, which aids in self-injection and ensures the passive activation of a needle guard.

Another form of Guselkumab used in the trial is a **solution for infusion**, with a concentration of 10 mg/mL. This formulation is administered via **intravenous use**. The maximum treatment period for this form is 12 weeks. The infusion is part of the trial's strategy to evaluate the efficacy and safety of Guselkumab in pediatric participants with moderately to severely active **ulcerative colitis**. The infusion does not involve any specific device for administration.

Additionally, the trial includes a placebo group, utilizing Guselkumab placebo formulations. These include the Guselkumab 2 mL PFS Placebo, Guselkumab 0.5 mL Varioject Placebo, and Guselkumab 1 mL PFS Placebo. These placebo formulations do not contain the active substance and are used to maintain the double-blind nature of the study. The placebo is administered in a manner consistent with the active treatment to ensure blinding is maintained throughout the trial.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The trial aims to assess the efficacy, safety, and pharmacokinetics of Guselkumab in the specified patient population, with a focus on those who respond to induction therapy. The trial is conducted in a randomized, open-label induction, double-blind maintenance, parallel-group, multicenter format.

The efficacy of **guselkumab** in pediatric participants with moderately to severely active **ulcerative colitis** will be assessed in a Phase 3 clinical trial. The primary endpoint for evaluating efficacy is clinical remission, as determined by the modified Mayo score, at Week 56. This endpoint will be measured among participants who respond to induction therapy. The modified Mayo score is a validated scale used to assess disease activity in ulcerative colitis, focusing on stool frequency, rectal bleeding, and endoscopic findings.

Participants will be evaluated at the end of the maintenance therapy phase, which lasts up to 56 weeks. The trial will employ a randomized, open-label induction and double-blind maintenance design, ensuring that the assessment of efficacy is both rigorous and unbiased. The trial will include pediatric participants aged 2 to less than 18 years, who have a documented diagnosis of ulcerative colitis and meet specific inclusion criteria related to disease severity and treatment history. The use of validated scales and central review of endoscopy videos will ensure the accuracy and reliability of the efficacy assessments.