Efficacy and Safety Evaluation of Tulisokibart in Moderate to Severe Crohn's Disease: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of tulisokibart compared with placebo in participants with moderately to severely active **Crohn's Disease**. This is assessed by the proportion of participants achieving clinical remission per Crohn’s Disease Activity Index score at Week 12. This objective is clinically relevant as achieving clinical remission is a critical goal in the management of Crohn's Disease, aiming to improve patient outcomes and quality of life.

Secondary objectives include: - Evaluating the efficacy of tulisokibart compared with placebo in the Dx+ subpopulation as assessed by the proportion of participants with Crohn’s Disease Activity Index clinical remission at Week 12. - Assessing the proportion of participants with endoscopic response at Week 12. - Evaluating the safety and tolerability of tulisokibart. - Assessing the efficacy of tulisokibart compared to placebo as evaluated by the proportion of participants achieving clinical remission per stool frequency and abdominal pain score at Week 12. - Evaluating the efficacy of tulisokibart compared with placebo as assessed by the proportion of participants achieving clinical remission per Crohn’s Disease Activity Index score at Week 12. - Assessing the proportion of participants with a decrease of at least 100 points in Crohn’s Disease Activity Index score from baseline at Week 12. - Evaluating the efficacy of tulisokibart compared with placebo as assessed by the mean change from baseline in the Functional Assessment of Chronic Illness Therapy – Fatigue at Week 12. - Assessing the proportion of participants with endoscopic remission at Week 12. - Evaluating the efficacy of tulisokibart compared with placebo as assessed by the mean change from baseline in IBDQ at Week 12. - Assessing the proportion of participants with a decrease of at least 100 points in Crohn’s Disease Activity Index from baseline at Week 6. - Evaluating the efficacy of tulisokibart compared with placebo as assessed by the proportion of participants with ulcer-free endoscopy at Week 12.

The clinical trial involves a total of **633 participants** diagnosed with **Crohn's Disease**. The study population includes both male and female subjects, with an age range of 16 years and older. Participants were selected based on their diagnosis of moderately to severely active Crohn's Disease, with a history of inadequate response, loss of response, or intolerance to certain categories of drugs, including oral locally acting steroids, systemic steroids, immunomodulators, biologic, and small molecule advanced therapies. The trial does not include a vulnerable population. Lifestyle considerations such as diet, physical activity, or habits are not specified. The selection criteria ensure that the study population is representative of individuals who have experienced challenges in managing their condition with existing treatments.

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of **tulisokibart** in participants with moderately to severely active **Crohn's Disease**. The trial aims to assess the proportion of participants achieving clinical remission and endoscopic response at Week 12. The study will involve the administration of tulisokibart via **intravenous infusion** and **subcutaneous injection**, with a placebo group for comparison. The trial is expected to commence recruitment on September 1, 2025, and conclude by February 28, 2033.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of Crohn's Disease at least three months prior, and an inadequate response or intolerance to certain medications. The trial will include follow-up visits to monitor the participants' progress and assess primary and secondary endpoints, such as clinical remission and adverse events. The end-of-study visit will mark the completion of the trial for each participant.

The expected duration of participant involvement is approximately 12 weeks, with conditions for early termination including adverse events or withdrawal of consent. The trial will ensure that all procedures adhere to regulatory standards, maintaining the integrity and scientific validity of the study outcomes.

The clinical trial involves the administration of **tulisokibart**, a biological investigational medication, in two different pharmaceutical forms. The first form is a **concentrate for solution for infusion**, which is administered via **intravenous infusion**. The active substance, tulisokibart, is a protein of other origin, developed by Merck & Co. Inc. The dosage is measured in milligrams, although specific dosing amounts are not provided. The maximum treatment period for this form is one unit of time, as defined by the trial protocol. Participant compliance with the dosing schedule will be monitored throughout the study.

The second form of tulisokibart is a **solution for injection in a pre-filled injector**, administered through **subcutaneous injection**. Similar to the intravenous form, the active substance is tulisokibart, a protein of other origin, and is also developed by Merck & Co. Inc. The dosage is again measured in milligrams, with the same maximum treatment period of one unit of time. Compliance with the administration schedule will be closely monitored to ensure adherence to the trial protocol.

A **placebo** is also utilized in this study as a comparator treatment. The placebo is designed to match the investigational product, MK-7240, in appearance and administration method, although it contains no active substance. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo will be administered following the same schedule and route as the investigational product to maintain consistency across the study arms.

The efficacy of the investigational product, **tulisokibart**, in the treatment of moderately to severely active Crohn's Disease will be assessed through a series of predefined endpoints. The primary efficacy endpoints include the proportion of participants achieving clinical remission as measured by the Crohn's Disease Activity Index (CDAI) score at Week 12, the proportion of participants achieving clinical remission based on stool frequency and abdominal pain score at Week 12, and the proportion of participants achieving an endoscopic response at Week 12. These assessments will be conducted in a randomized, double-blind, placebo-controlled trial setting.

Secondary efficacy endpoints will further evaluate the treatment's impact, including the percentage of participants in the diagnostic assay positive subpopulation achieving clinical remission per CDAI at Week 12, and the percentage achieving an endoscopic response at Week 12. Additional secondary measures include the number of participants experiencing adverse events, the number of participants discontinuing the study intervention due to adverse events, and the percentage of participants with a decrease of ≥100 points in CDAI score from baseline to Week 12. Other secondary endpoints include mean changes from baseline in the FACIT-Fatigue Score and the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 12, as well as the percentage of participants achieving endoscopic remission and ulcer-free endoscopy at Week 12.