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

The primary objective of this study is to evaluate the **efficacy** of different doses of SAR441566 on clinical remission in participants with moderate-to-severe **Ulcerative Colitis** (UC). Clinical remission is a critical endpoint in UC management, as it indicates a significant reduction or absence of symptoms, improving patient quality of life and reducing the risk of complications.

Secondary objectives include:

• Assessing the effect of different doses of SAR441566 on clinical response, clinical remission, and endoscopic remission in participants with moderate-to-severe UC.
• Evaluating the impact on patient-reported outcomes (PRO) remission, endoscopic response or improvement, and histologic improvement based on histologic endoscopic mucosal improvement (HEMI).
• Investigating the pharmacokinetics (PK) of SAR441566 and its safety and tolerability in the study population.
• Assessing the effect on PRO/signs and symptoms of UC and the inflammatory bowel disease questionnaire (IBDQ) response and remission.

The clinical trial involves a total of **258 participants** diagnosed with **Ulcerative Colitis**. The study population comprises both male and female subjects, aged between 18 to 75 years. Participants were selected based on their clinical evidence of active moderate-to-severe Ulcerative Colitis, confirmed by endoscopy, and a modified Mayo Score ranging from 5 to 9. The trial does not include a vulnerable population. Participants must have a history of inadequate response or intolerance to standard treatments or advanced therapies for Ulcerative Colitis. Lifestyle considerations such as diet and physical activity are not specified. The selection criteria ensure that participants have a significant history of the disease and previous treatment attempts, aligning with the study's objective to assess the efficacy of different doses of SAR441566 on clinical remission in this patient group.

The clinical trial is a **Phase 2**, multinational, multicenter, randomized, double-blind, placebo-controlled, dose-ranging study designed to evaluate the efficacy and safety of SAR441566 in adults with moderate-to-severe **ulcerative colitis**. The primary objective is to assess the efficacy of different doses of SAR441566 on clinical remission in participants with moderate-to-severe ulcerative colitis. The trial is expected to commence recruitment on May 25, 2025, and conclude by September 14, 2028.

Participants will be involved in the study for a duration that includes a screening period, treatment period, and follow-up visits. The inclusion visit, or screening, will confirm eligibility based on criteria such as age, clinical evidence of active ulcerative colitis for at least three months, and a modified Mayo Score indicating moderate-to-severe disease. The primary endpoint is the proportion of participants achieving clinical remission at Week 12, assessed by the modified Mayo Score. Secondary endpoints include various measures of clinical response and remission, endoscopic outcomes, and safety assessments.

Study visits will be scheduled at regular intervals to monitor the participants' health and response to the treatment. These visits will include assessments of clinical and endoscopic remission, patient-reported outcomes, and plasma concentrations of SAR441566. The end-of-study visit will occur after the final treatment period, where comprehensive evaluations will be conducted to assess the overall outcomes and safety of the intervention.

Participant involvement is expected to last until the end of the study unless early termination is warranted. Conditions for early termination include the occurrence of significant adverse events, withdrawal of consent, or any other medical or personal reasons deemed appropriate by the study investigators. The trial is structured to ensure rigorous monitoring and adherence to ethical standards throughout its duration.

The clinical trial involves the evaluation of **SAR441566**, an experimental medication developed by **SANOFI AVENTIS RECHERCHE ET DEVELOPPEMENT (SAR)**. SAR441566 is a chemical substance intended for the treatment of moderate-to-severe **ulcerative colitis**. The pharmaceutical form, dosage, route, and frequency of administration for SAR441566 are not specified in the provided data. The primary objective of the trial is to assess the efficacy of different doses of SAR441566 on clinical remission in participants with moderate-to-severe ulcerative colitis.

In addition to the experimental medication, a **placebo** is utilized as a comparator treatment in this double-blind, placebo-controlled study. The placebo is used to ensure that the effects observed in the trial can be attributed to SAR441566 rather than other factors. The placebo is administered in a manner consistent with the experimental medication to maintain the study's blinding and integrity. Details regarding the pharmaceutical form, dosage, and administration of the placebo are not provided in the data.

The efficacy of SAR441566 in the treatment of moderate-to-severe **Ulcerative Colitis** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of participants achieving clinical remission at Week 12, as determined by the modified Mayo Score (mMS). Secondary endpoints include the proportion of participants achieving clinical response and remission at Week 12 by both the modified Mayo Score and the full Mayo Score. Additionally, the study will evaluate the proportion of participants achieving a combination of patient-reported outcome 2 (PRO2) remission and endoscopic remission, as well as endoscopic response and improvement at Week 12.

Further secondary endpoints involve changes from baseline in PRO2 from randomization to Week 12, the proportion of participants achieving HEMI at Week 12, and plasma concentrations of SAR441566 at selected visits. The study will also monitor the number of participants experiencing treatment-emergent adverse events (TEAEs) during both the induction and maintenance treatment periods, as well as during the open-label treatment period. The proportion of participants achieving remission and response as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 12 will also be assessed. These efficacy parameters will be collected and analyzed at specified timepoints, primarily focusing on Week 12, using validated scales and laboratory tests where applicable.