Efficacy and Safety Evaluation of SAR441566 in Adults with Moderate to Severe Crohn's Disease: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** and dose response of different doses of SAR441566 on endoscopic response at the end of induction treatment in participants with moderate to severe **Crohn's Disease** (CD). This is clinically relevant as endoscopic response is a critical marker of disease activity and treatment success in CD, providing insights into the potential of SAR441566 to induce mucosal healing.

Secondary objectives include: - Assessing the effect of different doses of SAR441566 on clinical remission, patient-reported outcomes, and signs and symptoms of CD at the end of induction treatment. - Evaluating the composite endpoint of clinical remission and endoscopic response, as well as endoscopic remission and clinical response. - Investigating the impact on disease-specific quality of life (QOL) and pharmacokinetics (PK) of SAR441566. - Assessing the safety and tolerability of different doses of SAR441566. These objectives aim to provide a comprehensive understanding of the therapeutic potential and safety profile of SAR441566 in managing moderate to severe CD.

The clinical trial involves a total of **351 participants** diagnosed with **Crohn's disease**, specifically targeting those with moderate to severe conditions. The study population includes both male and female participants, aged between **18 to 75 years**. Participants were selected based on a confirmed diagnosis of Crohn's disease for at least three months prior to the baseline, with a history of prior exposure to standard or advanced therapies, yet demonstrating inadequate response or intolerance to at least one of these treatments. The trial does not include a vulnerable population. Participants are required to be on stable doses of standard treatments prior to screening, and contraceptive use must align with local regulations. The study does not include pregnant or breastfeeding women. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is a **randomized**, double-blind, placebo-controlled, dose-ranging study designed to evaluate the efficacy and safety of SAR441566 in adults with moderate to severe **Crohn's disease**. The trial aims to assess the efficacy and dose response of different doses of SAR441566 on endoscopic response at the end of the induction treatment. The study will involve male and female participants aged 18 to 75 years with a confirmed diagnosis of Crohn's disease for at least three months prior to baseline. Participants must have a history of prior exposure to standard or advanced therapies with inadequate response or intolerance to at least one of these therapies. The trial will be conducted over an estimated duration until May 2029, with recruitment starting in February 2025.

Participants will be involved in the study for a maximum treatment period of 104 weeks. The study will include several key visits: an inclusion (screening) visit to confirm eligibility, multiple follow-up visits to monitor progress and collect data, and an end-of-study visit to assess the final outcomes. The primary endpoint is the proportion of participants achieving endoscopic response, while secondary endpoints include clinical remission based on the Crohn's Disease Activity Index (CDAI), patient-reported outcome remission, and other clinical and endoscopic measures.

Participants will receive either SAR441566 or a matching placebo in the form of a **film-coated tablet** administered orally. The maximum daily dose of SAR441566 is 400 mg, with a total maximum dose of 291.20 g over the treatment period. Conditions that may lead to early termination from the study include serious adverse events, non-compliance with study procedures, or withdrawal of consent. The trial is not categorized as low intervention and is classified as a Phase 2 study. The study will ensure that contraceptive use by participants is consistent with local regulations, and women participants should not be pregnant or breastfeeding during the trial.

The clinical trial involves the administration of **SAR441566**, an experimental medication formulated as a **film-coated tablet**. The active substance, SAR441566, is of chemical origin and is developed by Sanofi Aventis Recherche et Développement (SAR). The medication is administered **orally** with a maximum daily dose of 400 mg. The total maximum dose over the treatment period is 291.20 grams. The treatment duration is set for a maximum of 104 weeks. The study aims to evaluate the efficacy and safety of SAR441566 in adults with moderate to severe **Crohn's disease**. Participant compliance with the dosing schedule will be monitored throughout the trial.

The study also includes a **placebo** group, which receives a matched placebo to the test product. The placebo is designed to mimic the appearance of the SAR441566 film-coated tablet but contains no active substance. The placebo administration follows the same oral route and dosing schedule as the experimental medication to maintain the double-blind nature of the trial. This comparator treatment is essential for assessing the true efficacy of SAR441566 by providing a baseline for comparison.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of participants achieving an endoscopic response at the end of the induction treatment. Secondary endpoints include the proportion of participants achieving clinical remission based on the **Crohn's Disease Activity Index (CDAI)**, Patient-Reported Outcome (PRO-2) remission, and both clinical remission and endoscopic response. Additional secondary endpoints involve the proportion of participants achieving endoscopic remission based on centrally read Simple Endoscopic Score for Crohn's Disease (SES-CD), CDAI clinical response, and remission or response as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ). Changes from baseline in IBDQ scores will also be evaluated.

Plasma concentrations of SAR441566, both pre-dose and post-dose, will be measured at selected visits to assess pharmacokinetics. The number of participants experiencing any treatment-emergent adverse events (TEAEs), including serious opportunistic infections, psoriasiform skin lesions, or other immune-mediated phenomena, will be recorded during both the double-blind induction and maintenance treatment periods, as well as the open-label treatment period. These efficacy parameters will be collected and analyzed at specified timepoints throughout the trial to determine the efficacy of SAR441566 in treating moderate to severe Crohn's disease.