A Randomized Controlled Trial on Fecal Microbiota Transplantation Versus Sodium Chloride for Recurrent Pouchitis in Ulcerative Colitis with IPAA

The primary objective of this study is to compare the **relapse** delay after fecal microbiota transplantation versus sham transplantation for recurrent **pouchitis** in patients with ileal pouch-anal anastomosis (IPAA) for **ulcerative colitis**. This is clinically relevant as it aims to determine the efficacy of fecal microbiota transplantation in prolonging the time to relapse, potentially offering a novel therapeutic approach for managing recurrent pouchitis, a common complication in patients with IPAA.

Secondary objectives include evaluating the efficacy of fecal microbiota transplantation on the relapse rate at week 24 and week 52, assessing the need for alternative treatment within 52 weeks, and determining the safety of fecal microbiota transplantation in cases of pouchitis. Additionally, the study aims to observe the modification of the fecal microbiota in patients with recurrent pouchitis in remission after antibiotic therapy following fecal microbiota transplantation from a healthy donor at week 8, and to evaluate the evolution of health-related disability. These objectives are crucial for understanding the broader impacts of fecal microbiota transplantation on patient outcomes and safety.

The clinical trial involves **patients** who have undergone ileal pouch anal anastomosis (IPAA) for **ulcerative colitis** and are experiencing active recurrent pouchitis. The study population includes both male and female participants aged 18 years and older. Participants must have been operated with an IPAA for at least six months prior to the screening visit and must be in remission with a Pouchitis Disease Activity Index (PDAI) of less than 7 at screening. The trial does not include a vulnerable population. Participants are required to have had at least two episodes of recurrent pouchitis in the last year or a relapse immediately after a reasonable response to antibiotherapy. Female participants of childbearing potential must have a negative pregnancy test at screening and agree to use effective contraception methods. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy of **fecal microbiota transplantation** (FMT) in preventing recurrent pouchitis in patients with ileal pouch-anal anastomosis (IPAA) for **ulcerative colitis**. The trial will compare the delay in relapse between FMT and a sham transplantation. The study is expected to run from March 2020 to May 2026, with participants involved for a maximum of 104 weeks post-transplantation. The trial will include several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the screening visit, eligibility will be assessed based on criteria such as age, previous IPAA surgery, and a history of recurrent pouchitis. Follow-up visits will occur at weeks 8, 24, and 52, with additional unscheduled visits as needed to monitor the Pouchitis Disease Activity Index (PDAI) and other health parameters. The primary endpoint is the delay between transplantation and clinical relapse, defined by a PDAI score of 7 or higher. Secondary endpoints include relapse rates at weeks 24 and 52, the time to initiation of alternative treatments, and the assessment of adverse events. Participants may be withdrawn from the study if they experience significant adverse events or fail to adhere to the protocol. The trial will utilize fresh donor feces for FMT and 0.9% sodium chloride as a comparator, both administered via intestinal routes. The study aims to provide valuable insights into the management of recurrent pouchitis in this patient population.

The clinical trial involves the administration of **allogeneic faecal microbiota** as an experimental treatment. This substance is provided in the form of a **suspension for endoscopic administration**. The product, known as "Fresh donor faeces (faecal matter)," is intended for **intestinal use**. The maximum daily dose is 50 grams, with a total treatment period of one day. The administration is conducted under controlled conditions to ensure participant safety and adherence to the study protocol. Compliance with the dosing schedule is monitored through direct observation and documentation by the clinical staff.

In addition to the experimental treatment, the study utilizes a comparator treatment consisting of a **0.9% Sodium Chloride Intravenous Infusion Solution**. This solution is classified as a **solution for infusion** and is also administered for **intestinal use**. The sodium chloride solution serves as a sham transplantation to evaluate the efficacy of the faecal microbiota transplant. The maximum daily dose is similarly set at 50 grams, with a treatment period of one day. The administration of the sodium chloride solution is performed in a manner consistent with standard clinical practices, ensuring the blinding of participants and investigators to the treatment allocation.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint is the delay between the date of transplantation and the date of clinical and endoscopic relapse, defined by a **Pouchitis Disease Activity Index (PDAI)** score of 7 or higher. Secondary endpoints include relapse at week 24 and week 52, also defined by a PDAI score of 7 or higher. Additional secondary endpoints involve the delay between transplantation and the initiation of antibiotherapy or alternative treatments, the registration of adverse events over 104 weeks post-transplantation, and fecal microbiota engraftment at 8 weeks. The latter will be assessed using Sorensen’s index, with fecal microbiota composition analyzed through 16S sequencing technology. The IBD Disability Index will also be evaluated at multiple timepoints, including weeks -2, baseline, 8, 24, 52, and during any unscheduled visits.