Evaluation of Amoxicillin-Clavulanic Acid Followed by Allogeneic Fecal Microbiota Transplantation in Moderate to Severe Hidradenitis Suppurativa Patients

The primary objective of this study is to evaluate the **effectiveness** of the amoxicillin-clavulanic acid antibiotic strategy followed by fecal microbiota transplantation (FMT) on disease activity at the 12th week post-FMT in patients with recurrent moderate to severe **Hidradenitis suppurativa** (HS) after treatment conducted according to French recommendations. This is clinically relevant as it aims to assess a potential therapeutic approach for managing HS, a chronic inflammatory skin condition characterized by painful nodules and abscesses, which significantly impacts patients' quality of life.

Secondary objectives include:

• Evaluating the effectiveness of the antibiotic strategy amoxicillin-clavulanic acid then FMT on disease activity (IHS4-55) at the 24th week post-FMT.
• Assessing the effectiveness of the amoxicillin-clavulanate antibiotic strategy followed by short- and medium-term FMT on disease activity (HSPGA) at 12 and 24 weeks post-FMT.
• Evaluating the impact of the antibiotic strategy on pain (pain VAS) and flow (VAS flow) at 12 and 24 weeks post-FMT.
• Assessing the quality of life (DLQI) of patients at the 12th and 24th week post-FMT and its evolution compared to the initial state.
• Evaluating the tolerance of FMT.
• Assessing changes in the fecal microbiota of patients at the 12th week post-FMT compared to inclusion.
• Identifying microbial factors in the fecal microbiota of donors that may have a positive or negative impact on patient outcomes, to define criteria for selecting an optimal stool donor in the context of this pathology.

The clinical trial focuses on patients diagnosed with **hidradenitis suppurativa**, specifically those with recurrent moderate to severe forms of the condition. The study population includes both male and female participants aged 18 years and older. Participants are required to have a Hurley stage II or III classification, with either an "axillo-mammary" or "gluteal" phenotype, and must present with at least four inflammatory lesions such as nodules, abscesses, or active fistulas. The trial does not involve a vulnerable population. Participants must have experienced at least one relapse following a well-conducted medical treatment as per the French recommendations, which includes broad-spectrum antibiotic therapy followed by prophylactic treatment. Additionally, participants must be able to speak and understand French. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the effectiveness of a treatment strategy involving **allogeneic faecal microbiota** transplantation in patients with recurrent moderate to severe **hidradenitis suppurativa**. This study is a Phase 4, randomized, double-blind, controlled trial. The trial aims to assess the improvement in disease activity at the 12th week post-transplantation, with a primary endpoint of achieving at least a 55% improvement in the IHS4 score. Secondary endpoints include further assessment of the IHS4 score at 24 weeks, improvement in HiSCR50 score, pain, quality of life, and analysis of fecal microbiota.

The trial is expected to commence recruitment on May 1, 2025, and conclude by May 1, 2030. Participants will be involved in the study for a duration of approximately 24 weeks. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age, disease severity, and language proficiency; a baseline visit for initial assessments and treatment initiation; follow-up visits at 12 and 24 weeks post-transplantation to evaluate treatment efficacy and monitor for adverse events; and an end-of-study visit to conclude participation and gather final data.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The study will utilize a nanosuspension injection of the investigational product, with a maximum daily dose of 250 ml. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.

The clinical trial involves the administration of an **experimental medication** known as "Transplant microbiote fécal," which contains the active substance **allogeneic faecal microbiota**. This medication is provided in the form of a **suspension** and is administered via **nanosuspension injection**. The maximum daily dose is 250 ml, with a total maximum dose of 250 ml over the treatment period. The treatment is designed to be administered over a period of one day. The formulation is not specifically designed for pediatric use, and it is not classified as an orphan drug. The product is developed by CHU Clermont Ferrand and is identified by the sponsor product code "TMF Naso".

In addition to the experimental treatment, the study protocol includes the use of a **standard-of-care therapy** involving the antibiotic strategy of amoxicillin-clavulanic acid. This is administered prior to the fecal microbiota transplantation (FMT) to evaluate its effectiveness on disease activity in patients with recurrent moderate to severe **hidradenitis suppurativa**. The study aims to assess the impact of this combined treatment strategy on disease activity at the 12th week post-FMT. Participant compliance with the dosing schedule and administration is monitored throughout the trial to ensure adherence to the protocol.

The efficacy of the clinical trial titled "FESTIVAL_Fecal transplantation in Hidradenitis suppurativa: a pilot study" will be assessed using several primary and secondary endpoints. The primary endpoint is the improvement of at least 55% in the **IHS4** score, which evaluates the number of nodules, abscesses, and fistulas with weighting according to the lesion, compared to the baseline state at the 12th week post fecal microbiota transplantation (FMT). This assessment will occur at day 104, with a margin of plus or minus 2 days.

Secondary endpoints include the improvement of at least 55% in the IHS4 score at the 24th week post-FMT, and the improvement of at least 50% of lesions (nodules and abscesses) without new draining fistula or abscess, as measured by the HiSCR50 score at 12 and 24 weeks post-FMT. Additional secondary endpoints involve the improvement in the HSPGA score by 2 ranks, improvement in pain and flow as measured by the Visual Analogue Scale (VAS), and improvement in quality of life as measured by the Dermatology Life Quality Index (DLQI) at 12 and 24 weeks post-FMT. The trial will also monitor the number and type of side effects, including any adverse events linked to FMT, from the day of FMT until 6 months post-FMT.

Furthermore, the analysis of the fecal microbiota of patients will be conducted at inclusion and at the 12th week post-FMT by sequencing the gene encoding the RNA of the small 16S subunit of the bacterial ribosome (16S RNA). Similarly, the fecal microbiota of donors will be analyzed at the first stool donation using the same sequencing method. These assessments will provide comprehensive data on the efficacy of the treatment strategy in patients with recurrent moderate to severe Hidradenitis suppurativa.