Evaluation of Guselkumab Subcutaneous Induction Therapy in Patients with Moderately to Severely Active Crohn's Disease: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** of guselkumab subcutaneous induction therapy in achieving clinical remission and endoscopic response in participants with moderately to severely active **Crohn's Disease**. This is clinically relevant as achieving remission and endoscopic healing are critical goals in the management of Crohn's Disease, potentially improving patient outcomes and quality of life.

The clinical trial involves a total of **291 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 adults and adolescents. Participants were selected based on specific criteria, including having clinically active Crohn's disease or fistulizing Crohn's disease for at least three months, and endoscopic evidence of active ileocolonic Crohn's disease. Additionally, participants are either currently undergoing treatment with oral corticosteroids and/or immunomodulators, have a history of failure to respond to or tolerate these treatments, or have demonstrated a lack of response or intolerance to one or more biologic agents. The trial also includes a vulnerable population, indicating that special considerations are in place for the protection and ethical treatment of these individuals. Lifestyle factors such as diet and physical activity were not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, parallel-group, multicenter study aimed at evaluating the efficacy and safety of **guselkumab** subcutaneous induction therapy in participants with moderately to severely active **Crohn's disease**. The trial will span an estimated duration from July 2022 to March 2028, with the primary objective of assessing clinical remission and endoscopic response at Week 12. Participants will be randomly assigned to receive either guselkumab or a placebo, with the treatment administered via subcutaneous injection.

The study will commence with an inclusion (screening) visit to confirm eligibility based on criteria such as clinically active Crohn's disease of at least three months duration and endoscopic evidence of active ileocolonic disease. Participants must also have a history of treatment with oral corticosteroids and/or immunomodulators or a history of failure to respond to or tolerate these treatments. Following the screening, eligible participants will undergo a series of study visits, including baseline assessments and regular follow-up visits to monitor safety and efficacy outcomes. The end-of-study visit will conclude the participant's involvement, which is expected to last up to 96 weeks.

Participants may be subject to early termination from the study if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial's primary endpoints include achieving clinical remission and endoscopic response at Week 12, with secondary endpoints to be determined. The study will utilize a pre-filled syringe for the administration of guselkumab, ensuring consistent dosing and participant safety throughout the trial.

The clinical trial involves the administration of **Guselkumab**, a solution for injection in a pre-filled syringe, with a concentration of 100 mg/mL. This experimental medication is provided by Janssen-Cilag International N.V. and is intended for **subcutaneous use**. The pharmaceutical form is classified as an injection/infusion. The administration of Guselkumab is facilitated by a 2mL UltraSafe Plus™ Passive needle guard, which is assembled to the pre-filled syringe to enable manual injection and passive activation of the needle guard post-delivery. The maximum treatment period for Guselkumab is 96 weeks, with no specified maximum daily or total dose amount. The active substance, Guselkumab, is a protein of other origin, and the product is not formulated for pediatric use.

Another form of Guselkumab is also utilized in the trial, presented as a solution for injection in a pre-filled syringe. This version is housed in the YpsoMate device, a 2-step autoinjector that contains a pre-filled syringe with a permanently bonded ½" long needle, ensuring automatic dose delivery following manual device activation. This formulation is also intended for subcutaneous use and shares the same treatment period and dosing specifications as the previously mentioned form. The active substance remains Guselkumab, and it is similarly not a pediatric formulation.

The study includes a **placebo** for Guselkumab, which serves as a comparator treatment. The placebo is not associated with any active substance and does not have a specified pharmaceutical form or route of administration. It is used to maintain the double-blind nature of the trial, ensuring unbiased assessment of Guselkumab's efficacy and safety in participants with moderately to severely active **Crohn's disease**. The placebo is also not formulated for pediatric use.

The efficacy of **guselkumab** in the treatment of moderately to severely active Crohn's disease will be assessed in a randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial. The primary endpoints for evaluating efficacy include achieving clinical remission and endoscopic response at Week 12. These endpoints are critical in determining the effectiveness of the subcutaneous induction therapy with guselkumab.

Clinical remission will be measured using standardized clinical assessment tools, while endoscopic response will be evaluated through endoscopic examinations. The trial will involve participants with clinically active Crohn's disease or fistulizing Crohn's disease of at least three months' duration, with endoscopic evidence of active ileocolonic disease. Participants may be currently treated with oral corticosteroids and/or immunomodulators, or have a history of failure to respond to or tolerate these treatments, or have demonstrated lack of response to biologic agents.

The trial is designed to ensure rigorous assessment of the efficacy of guselkumab, with the primary endpoints being measured at a specific timepoint, Week 12, to provide clear and objective data on the treatment's impact on disease activity. The study will utilize validated scales and endoscopic evaluations to ensure the reliability and accuracy of the efficacy assessments.