Phase 3 Multicenter Randomized Double-Blind Trial of Ceftriaxone, Metronidazole, Rifampicin, and Moxifloxacin in Hurley Stage 2 Hidradenitis Suppurativa

The primary objective of this multicentric randomized double-blind Phase 3 trial is to demonstrate the **superiority** of a 3-week course of ceftriaxone+metronidazole treatment followed by 3 weeks of a rifampicin+moxifloxacin+metronidazole combination, and then 6 weeks of rifampicin+moxifloxacin (experimental treatment) over a 12-week course of tetracycline-derivative (control treatment) in patients with Hurley stage 2 **Hidradenitis Suppurativa** at week 12. This objective is clinically relevant as it aims to establish a more effective treatment regimen for patients suffering from this chronic inflammatory skin condition, potentially improving patient outcomes and quality of life.

Secondary objectives include:

• Measuring the clinical efficacy of the experimental treatment at weeks 6, 24, and 52.
• Assessing microbiological efficacy at week 12.
• Evaluating the impact on pain and quality of life.
• Quantifying the use of additional treatments.
• Characterizing the number of HS flares after clinical remission.
• Identifying prognosis markers of response to treatments.
• Evaluating clinical and biological tolerance.
• Identifying the emergence of multidrug resistance in the gut microflora.

The clinical trial involves participants diagnosed with **Hurley stage 2 active Hidradenitis Suppurativa**. The study population includes both male and female adults under the age of 60, with a **Body Mass Index (BMI)** of less than 35. Participants are required to have a history of recurrent inflammation, with at least four flares in the previous year, and must be able to complete the Dermatology Life Quality Index (DLQI). The trial does not include a vulnerable population. Participants must be affiliated with the French health system, excluding those receiving French state medical aid. The sponsor has not provided information regarding the total number of participants. Selection criteria include the availability of recent laboratory blood tests and the use of active contraception for individuals of childbearing potential. The trial population was selected based on specific clinical criteria, ensuring a consistent and relevant sample for the study's objectives.

The clinical trial is a **randomized**, **double-blind**, controlled study designed to evaluate the efficacy of an adapted antibiotic therapy in patients with Hurley stage 2 active **Hidradenitis Suppurativa**. The trial is structured as a Phase 3 interventional study, with an estimated duration extending until March 2027. The primary objective is to demonstrate the superiority of a specific antibiotic regimen over a 12-week course of a tetracycline derivative. The trial involves a sequence of treatments, starting with a 3-week course of **ceftriaxone** and **metronidazole**, followed by a 3-week combination of **rifampicin**, **moxifloxacin**, and metronidazole, and concluding with 6 weeks of rifampicin and moxifloxacin.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, clinical diagnosis, and disease severity. Follow-up visits will be scheduled to monitor treatment efficacy and safety, with assessments including the Physician Global Assessment, modified Sartorius score, and the International Hidradenitis Suppurativa Severity Score (IHS4). The primary endpoint is the percentage of patients achieving clinical remission at week 12, defined by a 90% improvement in the IHS4 score from baseline. Secondary endpoints include evaluations of lesion microbiome normalization, pain assessment, and quality of life measures.

The expected length of participant involvement is approximately 12 weeks, with conditions for early termination including adverse events or non-compliance with the study protocol. Safety assessments will focus on the description of adverse events related to treatments and protocol procedures, as well as the emergence of resistant bacterial strains in the gut microflora. The trial aims to provide comprehensive data on the efficacy and safety of the experimental treatment regimen compared to the control, contributing valuable insights into the management of Hurley stage 2 active Hidradenitis Suppurativa.

The clinical trial involves the administration of several experimental and non-experimental treatments to evaluate their efficacy in patients with Hurley Stage 2 Hidradenitis Suppurativa. The experimental treatment includes a combination of **ceftriaxone** and **metronidazole** for the initial 3 weeks, followed by a combination of **rifampicin**, **moxifloxacin**, and metronidazole for the subsequent 3 weeks, and finally, a combination of rifampicin and moxifloxacin for the remaining 6 weeks. The ceftriaxone is administered as **ROCEPHINE 1 g/3.5 ml**, a solution for injection, with a maximum daily dose of 2 grams, administered intramuscularly. Metronidazole is provided as **FLAGYL 250 mg**, a film-coated tablet, with a maximum daily dose of 1500 mg, administered orally. Rifampicin is administered as **RIFADINE 300 mg**, a hard capsule, with a maximum daily dose of 900 mg, also administered orally. Moxifloxacin is provided in several formulations, including **MOXIFLOXACINE SANDOZ 400 mg**, **IZILOX 400 mg**, and **Avalox® 400 mg**, all as film-coated tablets with a maximum daily dose of 400 mg, administered orally.

The control treatment involves the administration of **TETRALYSAL 150 mg**, a hard capsule containing **lymecycline**, with a maximum daily dose of 904 mg, administered orally over a 12-week period. This serves as the comparator treatment in the study.

Additionally, several placebo formulations are used in the trial to maintain blinding. These include capsules composed of various inert substances such as cornstarch, colloidal anhydrous silica, cochineal carmine, microcrystalline cellulose, and riboflavin. These placebo capsules are designed to mimic the appearance of the active treatment capsules and are administered orally.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen. The trial is conducted under a double-blind design to maintain the integrity of the study results.

The efficacy of the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the percentage of patients achieving clinical remission at week 12, defined by an improvement of 90% in the International Hidradenitis Suppurativa Severity Score (IHS4) from baseline. Secondary endpoints include various measures of efficacy and safety. Efficacy will be evaluated through physician assessments using the Physician Global Assessment (PGA), modified Sartorius score, and HS clinical Response (HiSCR), as well as the IHS4 at each visit. Additionally, the normalization of the worst lesion microbiome at week 12 compared to baseline will be assessed. Patient-reported outcomes will include pain evaluation using a visual analog scale, the number of painful days per month, and the Dermatology Life Quality Index (DLQI). The number of painkillers and antibiotic treatments prescribed for flares, the number of surgical drainages, and the time without flare of HS after remission will also be recorded. Prognostic markers of response to treatments will be identified.

Safety assessments will include the description of adverse events related to treatments and protocol procedures, as well as the emergence of extended spectrum betalactamase and carbapenemase-producing enterobacteriaceae, and vancomycin-resistant enterococci in the gut microflora. The trial will follow a schedule of assessments at specified timepoints, including baseline and week 12, to ensure comprehensive data collection and analysis. The use of validated scales and patient journals will facilitate the accurate measurement of these parameters throughout the trial duration.