Phase 3 Randomized Double-Blind Placebo-Controlled Study of Tulisokibart Efficacy and Safety in Moderately to Severely Active Crohn's Disease

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 52. This objective is clinically relevant as it aims to determine the potential of tulisokibart to induce remission in a chronic inflammatory condition, which can significantly improve patient outcomes and quality of life.

Secondary objectives include:

• Evaluating the efficacy of tulisokibart compared with placebo as assessed by the proportion of participants achieving clinical remission per stool frequency and abdominal pain score at Week 52.
• Assessing the efficacy of tulisokibart compared with placebo by the proportion of participants achieving endoscopic response at Week 52.
• 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 efficacy of tulisokibart compared with placebo 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 endoscopic response at Week 12.
• Assessing the safety and tolerability of tulisokibart.

The clinical trial for evaluating the efficacy of tulisokibart in treating **Crohn's Disease** involves a total of 573 participants. The study population includes both male and female subjects, with an age range of 16 to 65 years. 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 adolescent participants aged 16 to less than 18 years can participate if approved by the relevant country or regulatory health authority.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of **tulisokibart** in participants with moderately to severely active **Crohn's Disease**. The trial is structured into two main studies, each with specific objectives to assess the clinical remission and endoscopic response of participants at various time points, specifically at Week 12 and Week 52. The trial will involve the administration of tulisokibart via **subcutaneous injection** and **intravenous infusion**, with a placebo group for comparison. The investigational medicinal product is delivered using a 2.25-mL autoinjector, which is a single-use device designed to administer the entire deliverable volume from a pre-filled syringe.

The trial duration is estimated to conclude by February 28, 2033, with recruitment expected to start on October 15, 2024. Participants will be involved in the study for a maximum treatment period of 208 weeks for the subcutaneous injection and 24 weeks for the intravenous infusion. The study visits are sequenced to include an initial screening visit to confirm eligibility based on the inclusion criteria, which require a diagnosis of Crohn's Disease for at least three months and an inadequate response to previous treatments. Follow-up visits will be scheduled to monitor the participants' progress and assess the primary and secondary endpoints, including clinical remission and adverse events. The end-of-study visit will finalize the participants' involvement, ensuring all necessary data is collected and any remaining health concerns are addressed.

Participant involvement is expected to last up to 52 weeks, depending on the study arm and treatment response. Conditions that may lead to early termination from the study include the occurrence of adverse events, withdrawal of consent, or any protocol violations that compromise the integrity of the trial. The trial aims to provide comprehensive data on the safety and efficacy of tulisokibart, contributing to the understanding and management of Crohn's Disease.

The clinical trial involves the administration of **tulisokibart**, an investigational medicinal product, in two distinct pharmaceutical forms. The first form is a **solution for injection in a pre-filled injector**. This formulation is delivered via a 2.25-mL autoinjector, which is designed to administer the entire deliverable volume from a pre-filled glass syringe. The syringe is equipped with a stainless steel needle, a rigid needle shield, and a coated stopper, with silicon oil used for lubrication. The route of administration for this form is **subcutaneous injection**. The maximum treatment period for this formulation is 208 weeks. The dosing schedule and specific dosage amounts are not explicitly defined in the provided data.

The second form of **tulisokibart** is a **concentrate for solution for infusion**, intended for **intravenous infusion**. This formulation is also classified as a biological product. The maximum treatment period for this form is 24 weeks. As with the subcutaneous form, the specific dosing schedule and dosage amounts are not detailed in the available information.

A **placebo** is also utilized in this study, serving as a comparator to the active investigational product, **tulisokibart**. The placebo is designed to mimic the administration routes of the active drug, either subcutaneous or intravenous, depending on the study arm. The placebo's pharmaceutical form and specific characteristics are not detailed in the provided data.

The efficacy of **tulisokibart** in the treatment of moderately to severely active Crohn's Disease will be assessed through a series of primary and secondary endpoints. The primary endpoints include the percentage of participants achieving clinical remission as measured by the Crohn's Disease Activity Index (CDAI) score and stool frequency and abdominal pain score at Weeks 12 and 52. Additionally, the proportion of participants achieving an endoscopic response at these timepoints will be evaluated. These assessments will be conducted in both Study 1 and Study 2, with specific endpoints tailored to meet the requirements of regulatory bodies such as the US FDA and the EU EMA.

Secondary endpoints will further explore the efficacy of **tulisokibart** by examining the number of participants experiencing adverse events, the percentage of participants achieving a decrease of ≥100 points in CDAI score from baseline, and changes in patient-reported outcomes such as the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-Fatigue) score and the Inflammatory Bowel Disease Questionnaire (IBDQ) score. Endoscopic remission and ulcer-free endoscopy rates will also be assessed. These efficacy parameters will be measured at various timepoints, including Weeks 6, 12, and 52, to provide a comprehensive evaluation of the treatment's impact over time.