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

The primary objective of this study is to demonstrate the **superiority** of SAR441566 over placebo in participants with moderate to severe plaque psoriasis, specifically within the Naïve Targeted Immunotherapy Population (NTIP). This is clinically relevant as it aims to establish the efficacy of SAR441566 as a potential therapeutic option for individuals suffering from this chronic and often debilitating skin condition.

Secondary objectives include:

• Evaluating the efficacy of SAR441566 in plaque psoriasis compared to placebo in the NTIP.
• Assessing the safety of SAR441566.
• Investigating the pharmacokinetics of SAR441566 in participants with moderate to severe plaque psoriasis.

The clinical trial involves a total of **248 participants** diagnosed with **psoriasis**, specifically targeting individuals with moderate to severe plaque psoriasis. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including a diagnosis of moderate to severe plaque psoriasis for at least six months, with a **Psoriasis Area and Severity Index (PASI)** score of 12 or higher, a static Physician's Global Assessment (sPGA) score of 3 or higher, and a Body Surface Area (BSA) involvement of 10% or more. Additionally, candidates must be suitable for phototherapy or systemic therapy, have a total body weight of at least 50 kg, and a body mass index (BMI) between 18 and 35 kg/m². The trial includes a vulnerable population, ensuring a comprehensive assessment of the treatment's efficacy across diverse demographic groups. Lifestyle factors such as diet and physical activity were not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of SAR441566 in adults with moderate to severe **plaque psoriasis**. The trial will involve a dose-ranging approach to determine the optimal dosage of SAR441566. Participants will be randomly assigned to receive either the active treatment or a matched placebo, administered orally in tablet form. The trial is expected to last approximately 12 weeks, with the estimated recruitment start date set for January 15, 2024, and an estimated end date of April 24, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a Psoriasis Area and Severity Index (PASI) score of 12 or greater, a static Psoriasis Global Assessment (sPGA) score of 3 or greater, and a Body Surface Area (BSA) score of 10% or greater. Eligible participants must also be candidates for phototherapy or systemic therapy and have a total body weight of at least 50 kg with a body mass index (BMI) between 18 and 35 kg/m². Following the screening, participants will be randomized and begin the treatment phase, with follow-up visits scheduled to monitor efficacy and safety outcomes.

The primary endpoint of the trial is the proportion of participants achieving a 75% or greater improvement in PASI score (PASI75) at week 12. Secondary endpoints include the percent change in PASI from baseline to week 12, the proportion of participants with an sPGA score of 0 or 1 at week 12, and the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). Plasma concentrations of SAR441566 will also be measured pre-dose and post-dose to assess pharmacokinetics.

Participant involvement is expected to last for the duration of the 12-week treatment period, with conditions for early termination including the occurrence of significant adverse events or withdrawal of consent. The trial aims to demonstrate the superiority of SAR441566 over placebo in the targeted population, contributing valuable data to the understanding of treatment options for moderate to severe plaque psoriasis.

The clinical trial involves the administration of **SAR441566**, an experimental medication developed by Sanofi Aventis Recherche et Développement (SAR). SAR441566 is formulated as a **tablet** and is administered **orally**. The maximum daily dose is 400 mg, with a total maximum dose of 35,200 mg over a treatment period of up to 12 weeks. The active substance, SAR441566, is of chemical origin and is intended for use in adults with moderate to severe plaque psoriasis. The trial aims to evaluate the efficacy and safety of SAR441566 in this patient population.

In addition to the experimental medication, a **placebo** is used as a comparator in this double-blind, placebo-controlled study. The placebo is designed to match the test product in appearance and administration route, ensuring blinding is maintained throughout the trial. The placebo is administered orally in the same pharmaceutical form as SAR441566, which is a tablet. The use of a placebo allows for the assessment of the true efficacy and safety profile of SAR441566 by providing a baseline for comparison.

The efficacy of SAR441566 in the treatment of moderate to severe plaque psoriasis will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of participants achieving a 75% or greater improvement in the **Psoriasis Area and Severity Index (PASI)** score from baseline, known as PASI75, at week 12. Secondary endpoints include the PASI percent change from baseline to week 12, the proportion of participants with a static Psoriasis Global Assessment (sPGA) score of 0 (indicating complete clearance) or 1 (indicating minimal disease) at week 12, and the number of participants experiencing treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). Additionally, plasma pre-dose and post-dose concentrations of SAR441566 will be measured to evaluate pharmacokinetics.

These efficacy parameters will be collected and analyzed at specified timepoints, with the primary assessment occurring at week 12. The PASI and sPGA scores are validated scales commonly used in clinical trials for psoriasis to quantify disease severity and treatment response. The collection of plasma concentrations will involve laboratory tests to determine the pharmacokinetic profile of SAR441566. The study is designed as a Phase 2, international, multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial, ensuring rigorous evaluation of the drug's efficacy and safety in the target population.