Phase 2 Double-Blind, Placebo-Controlled Study on the Efficacy and Safety of SAR444656 in Adults with Moderate to Severe Hidradenitis Suppurativa

The primary objective of this Phase 2, double-blind, placebo-controlled study is to evaluate the **clinical efficacy** of SAR444656 in adult participants with moderate to severe **hidradenitis suppurativa** (HS). This is assessed by the reduction of abscess and inflammatory nodule (AN) count at Week 16. The clinical relevance of this objective lies in its potential to provide a new therapeutic option for managing HS, a chronic and painful skin condition characterized by recurrent abscesses and nodules.

Secondary objectives include:

• Evaluating the clinical efficacy of SAR444656 through other clinical assessments in participants with moderate to severe HS.
• Assessing the effect of SAR444656 on pain in participants with HS.
• Evaluating the safety profile of SAR444656 in participants with HS.
• Determining the pharmacokinetic profile of SAR444656 in adult participants with HS.

The clinical trial involves a total of **162 participants** diagnosed with **hidradenitis suppurativa**, a chronic skin condition. 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 history of signs and symptoms consistent with hidradenitis suppurativa for at least one year prior to baseline, and the presence of lesions in at least two distinct anatomic areas, with one area being classified as Hurley Stage II or III. Additionally, participants must have had an inadequate response to at least one month of oral antibiotic treatment for hidradenitis suppurativa. The trial population includes individuals who are considered vulnerable, and lifestyle considerations such as contraceptive use are aligned with local regulations for clinical studies. The selection process ensures that participants have a total abscess and inflammatory nodule count of five or more at the baseline visit, and a draining tunnel count of 20 or fewer. The study aims to evaluate the clinical efficacy of SAR444656 in reducing abscess and inflammatory nodule count at Week 16.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of SAR444656 in adult participants with moderate to severe **hidradenitis suppurativa**. The trial will involve a parallel-group treatment approach and is classified as a Phase 2 study. The primary objective is to assess the clinical efficacy of SAR444656 based on the reduction of abscess and inflammatory nodule (AN) count at Week 16. The trial is expected to commence recruitment on December 15, 2023, and conclude by July 17, 2026, with a maximum treatment period of 16 weeks for each participant.

Participants will be required to attend several study visits throughout the trial. The initial visit will be a screening visit to confirm eligibility based on specific inclusion criteria, such as a history of hidradenitis suppurativa for at least one year, presence of lesions in at least two distinct anatomic areas, and an inadequate response to prior oral antibiotic treatment. Following the screening, eligible participants will be randomized to receive either SAR444656 or a matched placebo, administered orally in the form of film-coated tablets. The maximum daily dose of SAR444656 is 100 mg, with a total dose not exceeding 11,200 mg over the treatment period.

Subsequent follow-up visits will be scheduled to monitor the participants' response to the treatment, assess any adverse events, and ensure compliance with the study protocol. These visits will include evaluations of the primary and secondary endpoints, such as the percent change from baseline in total AN count, proportion of participants achieving Hidradenitis Suppurativa Clinical Response 50 (HiSCR 50), and changes in the International Hidradenitis Suppurativa Severity Score System (IHS4). The end-of-study visit will mark the completion of the trial for each participant, during which final assessments will be conducted.

Participant involvement is expected to last for the duration of the 16-week treatment period, with additional time allocated for the screening and follow-up visits. Conditions that may lead to early termination from the study include the occurrence of serious adverse events, non-compliance with the study protocol, or withdrawal of consent by the participant. The trial will ensure that all procedures adhere to ethical standards and regulatory requirements, maintaining the integrity and scientific validity of the study outcomes.

The clinical trial involves the administration of **SAR444656**, an experimental medication developed by Sanofi Aventis Recherche et Développement (SAR). **SAR444656** is provided in the form of a **film-coated tablet** and is intended for oral administration. The active substance, also named **SAR444656**, is of chemical origin. Participants in the trial will receive a maximum daily dose of 100 mg, with the total dose not exceeding 11,200 mg over the course of the study. The treatment period is set for a maximum of 16 weeks. The primary objective of the trial is to evaluate the clinical efficacy of **SAR444656** in reducing the count of abscesses and inflammatory nodules in participants with moderate to severe hidradenitis suppurativa.

In addition to the experimental medication, a **matched placebo** is utilized as a comparator treatment in this double-blind, placebo-controlled study. The placebo is designed to mimic the appearance of the **SAR444656** film-coated tablet but does not contain any active pharmaceutical ingredients. The use of a placebo allows for the assessment of the true efficacy and safety profile of **SAR444656** by providing a baseline for comparison. Participants will be randomly assigned to receive either the experimental medication or the placebo, ensuring the integrity of the study's blinding process.

The efficacy of SAR444656 in the treatment of moderate to severe **hidradenitis suppurativa** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the percent change from baseline in the total abscess and inflammatory nodule (AN) count at Week 16. This measurement will provide a direct evaluation of the drug's impact on the reduction of these specific symptoms.

Secondary endpoints include several additional measures to further evaluate efficacy. These include the proportion of participants achieving Hidradenitis Suppurativa Clinical Response 50 (HiSCR 50), the proportion of participants achieving an AN count of ≤2, and the absolute change from baseline in the International Hidradenitis Suppurativa Severity Score System (IHS4). Other secondary endpoints involve the proportion of participants with improvement from baseline in Hurley Stage, the proportion achieving AN50 (at least 50% reduction in AN count relative to baseline), and changes in participant-reported daily worst pain using the HS-Skin Pain-Numerical Rating Scale (HS-Skin Pain-NRS). Additionally, the study will assess the change from baseline in the amount of analgesic used, the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs), as well as the plasma concentration of SAR444656.