Evaluation of Allogeneic Adipose-Derived Mesenchymal Stem Cells in Treating Draining Fistulas in Hidradenitis Suppurativa: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this clinical trial is to evaluate the **safety** of intralesional administration of expanded human allogeneic mesenchymal cells derived from adipose tissue in patients with **hidradenitis suppurativa**. This will be assessed in terms of Adverse Events and Serious Adverse Events related to the investigational drug. Additionally, the trial aims to determine the efficacy of this treatment compared to a control group, focusing on the combined remission of the draining fistula 24 weeks post-administration. The clinical relevance of this study lies in its potential to offer a novel therapeutic approach for managing hidradenitis suppurativa, a chronic and often debilitating condition.

Secondary objectives include: - Evaluating the clinical remission of the treated draining fistula, including the closure of all draining fistulous orifices at the study's onset. - Assessing symptoms such as suppuration, pain, functional limitation, itching, and bad smell of the treated draining fistula using a visual analog scale for each symptom. - Analyzing the perceived quality of life post-treatment compared to the control group, utilizing the Euroqol-5D scale. - Evaluating the pro-inflammatory biomarker profile at the systemic level and determining its relationship and modification with the study intervention.

The clinical trial involves participants diagnosed with **hidradenitis suppurativa**, a chronic skin condition. The study population includes both male and female subjects, aged between 18 and 70 years, who have been diagnosed with the condition for at least six months prior to inclusion. Participants are required to have a draining fistula with specific characteristics, including a minimum of one subcutaneous tract and one cutaneous drainage hole, with active drainage observed four weeks before inclusion. The trial does not involve a vulnerable population. Participants must have normal kidney and liver function, as well as a blood count and coagulation study within normal values. Additionally, individuals of childbearing potential must agree to use safe contraceptive methods throughout the study and the six-month follow-up period. The total number of participants is not provided, as the sponsor has not disclosed this information. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is a **randomized**, **double-blind**, placebo-controlled study designed to evaluate the safety and efficacy of **allogeneic adipose-derived adult mesenchymal stem cells expanded** in the treatment of draining fistulas in patients with **hidradenitis suppurativa**. The trial is structured in two phases, Phase I and Phase II, and is conducted at a single center. The estimated duration of the trial is approximately four years, with recruitment starting in March 2023 and the study expected to conclude by September 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as age, diagnosis, and medical history. Following successful screening, participants will be randomly assigned to receive either the investigational product or a placebo. The investigational product is administered via **intralesional use** as a **suspension for injection**. The primary objective is to assess safety in terms of adverse events and serious adverse events related to the investigational drug, while efficacy is evaluated by the combined remission of the draining fistula after 24 weeks.

Throughout the study, participants will attend regular follow-up visits to monitor safety and efficacy outcomes. These visits will include clinical assessments, laboratory tests, and imaging studies, such as ultrasound, to evaluate the anatomical characteristics and clinical remission of the treated fistula. The study also aims to assess changes in symptoms and health-related quality of life using validated scales and questionnaires. The end-of-study visit will occur at the conclusion of the follow-up period, which lasts up to 24 months post-intervention.

Participant involvement is expected to last for the entire duration of the study, including the follow-up period. However, conditions that may lead to early termination from the study include the occurrence of significant adverse events, withdrawal of consent, or non-compliance with study procedures. The trial is conducted in accordance with ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the use of **allogeneic adipose-derived adult mesenchymal stem cells expanded** as the experimental medication. This investigational product is formulated as a **suspension for injection** and is administered via **intralesional use**. The primary objective is to evaluate the safety and efficacy of these cells in treating draining fistulas in patients with **hidradenitis suppurativa**. The administration schedule and dosage are determined based on the study protocol, with a focus on monitoring adverse events and serious adverse events related to the investigational drug. The product is classified as an **Advanced Therapy Medicinal Product** and is not a pediatric formulation.

The study also includes a **placebo** comparator, which is a mixture consisting of 50% hyaluronic acid, 49% DMEM without phenol red, and 1% L-Alanine-L Glutamine. This mixture does not have a specific pharmaceutical form or route of administration detailed in the trial documentation. The placebo serves as a control to assess the efficacy of the experimental treatment by comparing outcomes between the treatment and control groups. Participant compliance with the dosing schedule is monitored throughout the trial to ensure the integrity of the study results.

The efficacy of the investigational treatment in this clinical trial will be assessed by evaluating the **combined remission** of the treated draining fistula in patients with hidradenitis suppurativa. This primary efficacy endpoint is defined by four criteria: closure of all draining fistulous orifices present at the time of patient inclusion, absence of suppuration after vigorous digital pressure on the fistula, absence of collections larger than 2 cm in the treated fistula as evaluated by blind ultrasound, and absence of inflammation as assessed by blind Doppler ultrasound in the two axes of the lesion. These assessments will be conducted 24 weeks post-administration of the investigational product.

Secondary efficacy endpoints include the anatomical characteristics of the treated draining fistula, such as location, dimensions, depth, and inflammatory activity. Clinical remission is also evaluated, defined as the closure of all draining fistula orifices and absence of suppuration after digital pressure. Symptom variations, including pain, functional limitation, pruritus, suppuration, and bad odor, will be measured using a visual analogue scale (VAS) throughout the follow-up period. Changes in health-related quality of life will be assessed using the Euroqol-5D-3L questionnaire. Additionally, pro-inflammatory biomarkers, including TNFa, IL17a, IL-1a, IL-6, IL1Ra, IL-8, and VEGF, will be determined in plasma.