A Phase 2b/3 Randomized, Double-blind, Placebo-Controlled, Parallel Group, Multicenter Protocol to Evaluate the Efficacy and Safety of Icotrokinra in Participants With Moderately to Severely Active Crohn's Disease

This Phase 2b/3 trial evaluates icotrokinra in participants with moderately to severely active Crohn's disease. The primary objective consists of three distinct components addressing different phases of treatment. In the Phase 2b induction phase, the primary objective is to evaluate the efficacy of icotrokinra versus placebo in inducing clinical response. In the Phase 3 induction phase, the primary objective is to evaluate the efficacy of icotrokinra versus placebo in induction treatment. In the Phase 3 maintenance phase, the primary objective is to evaluate the efficacy of icotrokinra versus placebo in maintenance treatment. These objectives are clinically relevant as they assess both the initial therapeutic response and the sustained efficacy of icotrokinra in managing this chronic inflammatory bowel disease, addressing both short-term symptom control and long-term disease management.

This clinical trial enrolled a total of **657 participants** diagnosed with **moderately to severely active Crohn's disease**. The study population included both **male** and **female** participants aged **18 years and older** (or the legal age of consent in the respective jurisdiction). All participants had a confirmed diagnosis of Crohn's disease established at least 12 weeks prior to screening, supported by endoscopic evidence of colitis, ileitis, or ileocolitis, and histopathology consistent with the diagnosis. Participants were required to demonstrate moderately to severely active disease based on **Crohn's Disease Activity Index (CDAI)** scores ranging from 220 to 450, with specific requirements for daily stool frequency or abdominal pain scores. Additionally, participants had to meet **Simple Endoscopic Score for Crohn's Disease (SES-CD)** criteria, with scores of at least 6 for colonic or ileocolonic disease and at least 4 for isolated ileal disease, based on the presence of ulceration in ileocolonic segments. The trial population was selected based on demonstrated inadequate response, loss of response, or intolerance to previous conventional therapies such as oral corticosteroids, thiopurines, or **methotrexate**, or to advanced therapies including **anti-TNFα antibodies**, anti-integrin antibodies, anti-interleukin 12/23 antibodies, or **JAK inhibitors**. No vulnerable populations were included in this study.

This is a 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 Crohn's disease. The study is structured as a Phase 2b/3 trial and consists of distinct induction and maintenance phases. The investigational medicinal product icotrokinra is administered as a film-coated tablet for oral use, and the active substance is a peptide. A matching placebo tablet is used as the comparator. The maximum treatment period is 260 days.

The primary objective of the Phase 2b induction phase is to evaluate the efficacy of icotrokinra versus placebo in inducing clinical response. The Phase 3 induction phase aims to evaluate the efficacy of icotrokinra versus placebo in induction, while the Phase 3 maintenance phase focuses on evaluating the efficacy of icotrokinra versus placebo in maintenance of response. The primary endpoint for Phase 2b induction is clinical response at Week I-12. The co-primary endpoints for Phase 3 induction are clinical remission at Week I-12 and endoscopic response at Week I-12. The co-primary endpoints for Phase 3 maintenance are clinical remission at Week M-40 and endoscopic response at Week M-40.

Eligible participants must be aged 18 years or older and have a diagnosis of Crohn's disease established at least 12 weeks before screening, confirmed by endoscopic evidence and histopathology consistent with the diagnosis. Participants must demonstrate moderately to severely active Crohn's disease based on Crohn's Disease Activity Index (CDAI) criteria, defined as a baseline CDAI score of 220 to 450, with either a mean daily stool frequency count of at least 4 or a mean daily abdominal pain score of at least 2. Additionally, participants must have moderately to severely active Crohn's disease based on Simple Endoscopic Score for Crohn's Disease (SES-CD) criteria, defined as an SES-CD of at least 6 for colonic or ileocolonic disease or at least 4 for isolated ileal disease, with specific minimum scores for ulceration components. Participants must have demonstrated an inadequate response, loss of response, or intolerance to previous conventional therapy or advanced therapy, including biologics or advanced oral agents for the treatment of Crohn's disease.

The estimated recruitment start date is December 15, 2025, and the estimated end date of the trial is October 6, 2032. The overall trial duration encompasses the screening period, induction phase, and maintenance phase, with participants potentially remaining in the study for up to 260 days of treatment. Specific details regarding the sequence of study visits, including screening visits, follow-up visits during the induction and maintenance phases, and end-of-study visits, are determined by the protocol design to assess efficacy and safety outcomes at defined time points. Conditions that may lead to early termination from the study are defined according to the protocol, including safety concerns, lack of efficacy, withdrawal of consent, or protocol violations.

The experimental medication **icotrokinra** (also designated as **JNJ-77242113**) is administered as a **film-coated tablet** formulation. The active substance is a **peptide** classified as protein-other in origin. The medication is administered via the **oral route**. The maximum treatment period for this investigational product is 260 weeks. The pharmaceutical form is manufactured by JANSSEN-CILAG INTERNATIONAL N.V.

A matching **placebo** tablet (designated as JNJ-77242113-AAC Placebo tablet) is utilized in this randomized, double-blind, placebo-controlled trial. The placebo serves as the comparator treatment to evaluate the efficacy and safety of the active investigational product in participants with moderately to severely active **Crohn's disease**. The study design includes both induction and maintenance phases, with the placebo administered to control groups during Phase 2b and Phase 3 portions of the trial.

Efficacy will be assessed using distinct primary endpoints across the different phases of the study. In the Phase 2b induction period, the primary endpoint is clinical response at Week I-12. For the Phase 3 induction period, two co-primary endpoints will be evaluated: clinical remission at Week I-12 and endoscopic response at Week I-12. In the Phase 3 maintenance period, efficacy will be assessed through two co-primary endpoints: clinical remission at Week M-40 and endoscopic response at Week M-40. Clinical response and remission will be evaluated based on Crohn's Disease Activity Index (CDAI) criteria, with baseline CDAI scores ranging from 220 to 450. Endoscopic assessment will utilize the Simple Endoscopic Score for Crohn's Disease (SES-CD), with baseline scores of at least 6 for participants with colonic or ileocolonic disease and at least 4 for those with isolated ileal disease. The SES-CD evaluation requires specific ulceration component scores, including a minimum score of 1 for the size of ulcers and a minimum score of 1 for the ulcerated surface across the five ileocolonic segments. Baseline endoscopic evidence will be assessed through central review of screening video ileocolonoscopy.