A Phase 3 Randomized, Double-blind, Placebo-Controlled, Parallel Group, Multicenter Protocol in Adults with an Open Label Study in Adolescents to Evaluate the Efficacy and Safety of Induction and Maintenance Therapy with Icotrokinra in Participants With Moderately to Severely Active Ulcerative Colitis

The primary objective of this trial is to evaluate the efficacy of icotrokinra in participants with moderately to severely active ulcerative colitis. In the induction study for adults, the primary objective is to assess the efficacy of icotrokinra versus placebo in inducing clinical remission. In the maintenance study for adults, the primary objective is to evaluate the efficacy of a maintenance regimen of icotrokinra versus placebo in achieving clinical remission in participants who were induced into clinical response with icotrokinra. For the adolescent study, the primary objective is to evaluate the efficacy of a maintenance regimen of icotrokinra in achieving clinical remission in adolescent participants with moderately to severely active ulcerative colitis who were induced into clinical response with icotrokinra. These objectives are clinically relevant as they assess both the induction and maintenance of clinical remission in a patient population with significant disease burden, evaluating the therapeutic potential of icotrokinra across different age groups and treatment phases.

This clinical trial enrolled a total of **491 participants** diagnosed with **moderately to severely active ulcerative colitis**. The study population included both **adult participants** aged 18 years and older, as well as **adolescent participants** aged 12 to 17 years at the time of enrollment. Both **male** and **female** subjects were eligible for participation. All participants were required to have an established diagnosis of ulcerative colitis for at least 12 weeks prior to screening, confirmed by endoscopic evidence and histopathology consistent with the condition. The trial population was selected based on disease activity, defined by a baseline modified Mayo score of 5 to 9 and an endoscopy subscore of at least 2 as determined by central review. Participants with extensive ulcerative colitis for 8 years or more, or disease limited to the left side of the colon for 10 years or more, were required to undergo colonoscopy with dysplasia assessment within one year before receiving the study intervention. The study included vulnerable populations as part of its enrollment criteria.

This is a **Phase 3**, **randomized**, **double-blind**, **placebo-controlled**, **parallel group**, **multicenter** clinical trial designed to evaluate the efficacy and safety of **icotrokinra** in participants with **moderately to severely active ulcerative colitis**. The study comprises an induction phase and a maintenance phase for adult participants, with an additional **open-label** study component for adolescent participants. The investigational medicinal product, icotrokinra, is administered as a **film-coated tablet** for **oral use**, with a maximum treatment period of 260 days. The **placebo** comparator is provided as a matching tablet. The trial is expected to commence recruitment in December 2025 and conclude in January 2032.

The primary objective of the induction study in adults is to evaluate the efficacy of icotrokinra versus placebo in inducing **clinical remission**. The maintenance study in adults aims to assess the efficacy of continued icotrokinra treatment versus placebo in achieving clinical remission in participants who responded to induction therapy. For adolescent participants, the study evaluates the efficacy of maintenance therapy with icotrokinra in achieving clinical remission following induction response. The **primary endpoint** for the adult induction study is clinical remission at Week I-12, while the primary endpoint for both the adult and adolescent maintenance studies is clinical remission at Week M-40.

Eligible participants must meet specific criteria to enter the study. Adult participants must be at least 18 years of age and of legal age of consent in their jurisdiction, while adolescent participants must be between 12 and 17 years of age at the time of informed assent or consent. All participants must have a confirmed diagnosis of **ulcerative colitis** established at least 12 weeks prior to screening, supported by endoscopic evidence and histopathology consistent with the diagnosis. Disease activity must be classified as moderately to severely active, defined by a baseline **modified Mayo score** of 5 to 9 inclusive, with an **endoscopy subscore** of at least 2 as determined by central review of screening video endoscopy. Participants with extensive ulcerative colitis for 8 years or more, or left-sided disease for 10 years or more, must undergo a complete **colonoscopy** to assess for **dysplasia** within one year before receiving the first dose of study intervention, which may be completed during the screening period.

The study involves a structured sequence of visits designed to assess participant eligibility, monitor treatment response, and evaluate safety throughout the trial duration. The screening visit serves as the inclusion assessment, during which participants undergo comprehensive evaluation including endoscopic procedures with central review to confirm disease severity and eligibility. Following successful screening and enrollment, participants enter the induction phase with scheduled follow-up visits to monitor clinical response and safety parameters. Participants who achieve clinical response during induction proceed to the maintenance phase, which includes regular follow-up visits to assess sustained remission and ongoing safety. The end-of-study visit occurs upon completion of the maintenance phase or upon early discontinuation. Participant involvement spans the duration of both induction and maintenance phases, with the potential for extended participation up to the maximum treatment period of 260 days. Early termination from the study may occur due to various conditions including lack of therapeutic response, adverse events, withdrawal of consent, protocol violations, or investigator discretion based on participant safety considerations.

The experimental medication evaluated in this clinical trial is **Icotrokinra**, also known by its sponsor product code **JNJ-77242113**. Icotrokinra is formulated as a **film-coated tablet** for **oral use**. The active substance, icotrokinra, is classified as a **peptide** with a protein origin. Alternative designations for this compound include JNJ-2113, PN-21235, and PN-235. The maximum treatment period for icotrokinra administration is 260 days. This investigational medicinal product is manufactured by Janssen-Cilag International N.V. and is being studied for both induction and maintenance therapy in participants with **moderately to severely active ulcerative colitis**. The study design includes evaluation in adult participants as well as an open-label component in adolescent participants.

The comparator treatment utilized in this trial is a **placebo** tablet designated as JNJ-77242113-AAC Placebo tablet. The placebo is administered to match the experimental treatment in the double-blind, placebo-controlled portions of the study. The placebo serves as the control arm in the induction study for adults and in the maintenance study for adults to evaluate the efficacy of icotrokinra versus no active treatment. The placebo formulation is designed to maintain blinding throughout the randomized, controlled phases of the trial.

Efficacy will be assessed using clinical remission as the primary endpoint. In the adult induction study, the primary efficacy endpoint is clinical remission at Week I-12. For the adult maintenance study, the primary efficacy endpoint is clinical remission at Week M-40. In the adolescent study, the primary efficacy endpoint is clinical remission at Week M-40. The evaluation of efficacy is based on the modified Mayo score, with baseline assessment requiring a score of 5 to 9, inclusive. The modified Mayo score incorporates an endoscopy subscore, which must be ≥2 as determined during central review of the screening video endoscopy. The study aims to evaluate the efficacy of icotrokinra versus placebo in inducing clinical remission in adults and to assess the efficacy of a maintenance regimen of icotrokinra in achieving clinical remission in both adult and adolescent participants with moderately to severely active ulcerative colitis who were induced into clinical response with icotrokinra.