Phase 2 Randomized, Double‑Blind, Placebo‑Controlled Dose‑Finding Study of Subcutaneous SAR445399 in Adults with Moderate to Severe Hidradenitis Suppurativa

The primary objective is to assess the efficacy of several dose levels of SAR445399 in adults with moderate to severe hidradenitis suppurativa, establishing the dose‑response relationship necessary for therapeutic evaluation. Secondary objectives are to confirm dose‑related efficacy, to determine the impact of dose variation on pain, to measure changes in quality of life, to characterize the safety and tolerability profile, to describe the pharmacokinetic behavior of SAR445399, and to evaluate the immunogenicity of the investigational product.

132 participants were enrolled, comprising both male and female individuals, including vulnerable subjects. The cohort included patients with a history of hidradenitis suppurativa lasting at least six months and with active lesions in a minimum of two distinct anatomical sites, one of which required Hurley Stage II or III disease. Eligible participants were required to have a baseline count of five or more abscesses and inflammatory nodules and to have demonstrated an inadequate response, recurrence, intolerance, or contraindication to oral antibiotic therapy. The population was stratified by prior biologic exposure, with biologic‑naïve subjects having no previous biologic treatment and biologic‑experienced subjects having received at least one dose of a biologic agent for the condition. Age eligibility encompassed the ranges represented by the study codes “3” and “4,” reflecting adult and adolescent age groups. All participants were patients meeting the specified disease severity and treatment‑history criteria.

The study is a Phase 2, dose-finding, randomized, double‑blind, placebo‑controlled trial evaluating the efficacy and safety of subcutaneous SAR445399 in adult participants with moderate to severe Hidradenitis suppurativa. After an initial screening visit to confirm eligibility, participants are randomized to receive SAR445399 or matching placebo and are followed for a 16‑week double‑blinded treatment period with visits at baseline (Week 0) and at Weeks 4, 8, 12, and 16 to assess clinical response, safety laboratory parameters, vital signs, ECGs, and pharmacokinetic sampling. The primary efficacy assessment is the proportion of participants achieving HiSCR75 at Week 16; secondary endpoints include HiSCR50, changes in IHS4, tunnel counts, pain scores, quality‑of‑life measures, and safety outcomes. Overall participant involvement spans approximately 18 weeks, including the screening window and the end‑of‑study visit at Week 16. Early termination may occur if a serious adverse event arises, a contraindicating condition develops, consent is withdrawn, or protocol compliance cannot be maintained.

The investigational product, SAR445399, is supplied as a powder for solution for injection/infusion and is administered by subcutaneous injection. Each dose is prepared to deliver 00.00 mg of the active substance and is given according to the study’s predefined dosing schedule, which may include multiple administrations over the treatment period.

The comparator in this double‑blind trial is a placebo consisting of an 8 mL solution for injection (product code PB0867488). The placebo contains no active pharmaceutical ingredient and is administered using the same route and schedule as the active product to maintain blinding.

All study medication and placebo are dispensed in a blinded manner, and dosing occurs at specified study visits. Participants receive the assigned injection under direct observation by study staff to ensure correct administration. Compliance is monitored through injection logs, accountability records, and verification of returned study material at each visit.

The primary efficacy assessment is the proportion of participants achieving Hidradenitis Suppurativa Clinical Response 75 (HiSCR75) at the end of the double‑blind treatment period.

Secondary efficacy assessments include the proportion achieving Hidradenitis Suppurativa Clinical Response 50 (HiSCR50) and Hidradenitis Suppurativa Clinical Response 90 (HiSCR90), the absolute and percent change from baseline to Week 16 in the International Hidradenitis Suppurativa Severity Score System (IHS4), and changes in draining tunnel count (both absolute and percent). Additional patient‑reported outcomes comprise the proportion with ≥3‑point improvement in the weekly average Hidradenitis Suppurativa Skin Pain Numeric Rating Scale (HS‑Skin Pain NRS) among those with baseline pain ≥3, the percent change in HS‑Skin Pain NRS, the absolute change in the Dermatology Life Quality Index (DLQI) total score, the absolute change in the Hidradenitis Suppurativa Quality of Life (HiSQoL) score, changes in weekly average HS‑SAQ items, change in the Hidradenitis Suppurativa Impact Assessment Questionnaire (HS‑IAQ) total score, and improvement in the Peak Pruritus Numerical Rating Scale (PP‑NRS) at Week 16.

Efficacy parameters are collected at baseline and at Week 16 using validated clinical response criteria and patient‑reported outcome instruments. The proportion of responders for each clinical response endpoint is calculated by comparing the number of participants meeting the predefined response definition to the total number randomized. Continuous endpoints (e.g., IHS4, DLQI, HiSQoL, HS‑Skin Pain NRS) are analyzed by evaluating the absolute or percent change from baseline to Week 16. All assessments are performed by blinded investigators according to the study protocol, and data are analyzed using appropriate statistical methods for categorical and continuous outcomes.