Phase 3 Multicenter Randomized Study of Guselkumab Efficacy and Safety in Pediatric Patients with Moderate to Severe Crohn's Disease

The primary objective of this Phase 3, multicenter, randomized study is to evaluate the **efficacy** and safety of **guselkumab** in pediatric participants with moderately to severely active **Crohn's Disease** (CD). This evaluation will occur at the end of the maintenance therapy phase among participants who demonstrated a clinical response to guselkumab at Week 12. The clinical relevance of this study lies in its potential to establish guselkumab as a viable treatment option for pediatric patients with CD, addressing a significant unmet need in this population.

The clinical trial involves a total of **58 participants** diagnosed with **Moderately to Severely Active Crohn's Disease**. The study population includes both male and female subjects, with an age range that encompasses pediatric participants. The trial population was selected based on specific inclusion criteria, which required participants to have a confirmed diagnosis of Crohn's Disease or fistulizing Crohn's Disease with active colitis, ileitis, or ileocolitis. Participants must have demonstrated moderately to severely active disease, as indicated by a baseline Pediatric Crohn's Disease Activity Index score greater than 30, and evidence of active disease through endoscopic assessment. The trial also considers participants' prior or current medication history, including inadequate response or intolerance to immunomodulators, corticosteroids, biologic therapy, or JAK inhibitors. The study includes a vulnerable population, reflecting the pediatric focus of the trial. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the **efficacy** and safety of **guselkumab** in pediatric participants with moderately to severely active **Crohn's disease**. This is a Phase 3, multicenter, randomized, double-blind, controlled study. The trial will involve a comparison between guselkumab and placebo, with the primary objective being to assess clinical remission and endoscopic response at Week 52. The study is expected to conclude by January 2028, with recruitment having commenced in March 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as a diagnosis of Crohn's disease with active colitis, ileitis, or ileocolitis, and a baseline Pediatric Crohn's Disease Activity Index (PCDAI) score greater than 30. Following the screening, participants will be randomized to receive either guselkumab or placebo. The trial includes multiple follow-up visits to monitor the participants' response to treatment and to ensure safety. The end-of-study visit will occur at Week 52, where the primary endpoints of clinical remission and endoscopic response will be evaluated.

The expected length of participant involvement is up to 52 weeks. Conditions that may lead to early termination from the study include adverse events, lack of efficacy, or withdrawal of consent. Participants will receive either subcutaneous or intravenous administration of the investigational product, with guselkumab being delivered via a solution for injection in a pre-filled syringe or as a solution for infusion. The study will utilize devices such as the VarioJect™ variable dose injector and the UltraSafe Plus™ Passive needle guard to facilitate drug delivery. The trial aims to provide valuable insights into the treatment of pediatric Crohn's disease, potentially improving therapeutic strategies for this condition.

The clinical trial involves the administration of **Guselkumab**, a monoclonal antibody, as the experimental medication. Guselkumab is provided in three different pharmaceutical forms: a solution for injection in a pre-filled syringe, a solution for infusion, and a solution for injection in a pre-filled syringe with a concentration of 100 mg/mL. The solution for injection in a pre-filled syringe is administered via **subcutaneous use**. The solution for infusion is administered via **intravenous use**. The maximum treatment period for Guselkumab is 52 weeks for the subcutaneous form and 12 weeks for the intravenous form. The administration of Guselkumab is facilitated by devices such as the VarioJect™ variable dose injector and the UltraSafe Plus™ Passive needle guard, which ensure accurate dosing and safety during administration.

In addition to the experimental medication, the study includes the use of a **placebo** as a comparator treatment. The placebo is available in three different volumes: 0.5 mL, 1.0 mL, and 2.0 mL equivalents. The pharmaceutical form and route of administration for the placebo are not specified. The placebo serves as a control to evaluate the efficacy and safety of Guselkumab in pediatric participants with Crohn's Disease. The study does not specify any additional non-experimental treatments or standard-of-care therapies.

The efficacy of the clinical trial will be assessed by evaluating the primary endpoints, which include clinical remission and endoscopic response at Week 52. Clinical remission is defined as a Pediatric Crohn's Disease Activity Index (PCDAI) score of ≤10. Endoscopic response is characterized by a ≥50% reduction from the baseline Simple Endoscopic Score for Crohn's Disease (SES-CD) score. These endpoints will be measured at the end of the maintenance therapy period among participants who were in clinical response to **guselkumab** at Week 12.

The trial will utilize validated scales such as the PCDAI and SES-CD to measure efficacy. The PCDAI is a widely recognized tool for assessing disease activity in pediatric Crohn's Disease, while the SES-CD provides a standardized method for evaluating endoscopic findings. The assessments will be conducted at specified timepoints, including Week 12 and Week 52, to determine the efficacy of **guselkumab** in achieving clinical remission and endoscopic response in pediatric participants with Crohn's Disease.