protocolSection identificationModule nctId: NCT06306014, orgStudyIdInfo id: 69HCL22_980, secondaryIdInfos id: 2023-506232-32-00, type: OTHER, domain: EU CT Number, briefTitle: Evaluation of EXL01, a New Live Biotherapeutic Product to Prevent Recurrence of Clostridioides Difficile Infection in High-risk Patients, acronym: LIVEDIFF, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-04-01, primaryCompletionDateStruct date: 2027-01-01, completionDateStruct date: 2027-01-01, studyFirstPostDateStruct date: 2024-03-12, lastUpdatePostDateStruct date: 2024-03-12, sponsorCollaboratorsModule leadSponsor name: Hospices Civils de Lyon, class: OTHER, collaborators name: Exeliom Biosciences, descriptionModule briefSummary: Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea in Europe, with over 120,000 cases and almost 3,700 deaths per year. This infection is characterized by a high risk of recurrence after cure, ranging from almost 20% after a first episode to over 60% after 2 recurrences, or in the case of specific risk factors.Currently, first-line treatment of CDI is based on oral antibiotics such as fidaxomicin or vancomycin. These antibiotic treatments, which are effective in 89% and 86% of first-episode cases respectively, do not correct the microbiological imbalance underlying the onset of CDI and may, on the contrary, encourage recurrence by contributing to the maintenance of a deleterious change in the microbiota (dysbiosis) through the elimination of bacteria other than C. difficile, due to their spectrum of activity. In a number of patients, this ecological imbalance can no longer be restored after antibiotic treatment, leading to multiple recurrences of CDI.In this context, fecal microbiota transplantation (FMT) has been validated for over 10 years for the prevention of recurrence in multi-recurrent CDI. The principle of FMT is based on the use of a pharmaceutical preparation made from the stool of a healthy donor, administered within the digestive tract of a patient for therapeutic purposes.Currently, in the case of multiple recurrences, it is the recommended first-line treatment (from 2 recurrences) and the most effective, with a clinical efficacy preventing recurrence of CDI in 69% to 89% of cases at 8 weeks post-treatment, with a good safety profile.Among the microbial factors promoting CDI, the loss of the bacterial species Faecalibacterium prausnitzii constitutes a specific therapeutic target. F. prausnitzii is a commensal bacterium of the human gut, making up nearly 5% of the fecal microbiota, and has been shown to be associated with an individual's state of health. A drop in its relative abundance is associated with an increased risk of numerous diseases, such as Crohn's disease and colorectal cancer. In CDI, F prausnitzii is greatly diminished. Moreover, low abundance of F. prausnitzii is predictive of C. difficile recurrence. Its abundance in stools is increased after FMT and is also predictive of response to treatment. From a pathophysiological point of view, one of the preventive effects of F. prausnitzii on recurrence would be mediated by its ability to hydrolyze the bile acids involved in the germination of C. difficile spores.The aim of this Phase I/II trial is to assess the efficacy and safety of oral administration of EXL01, a single isolated unmodified strain of F. prausnitzii, in preventing CDI recurrence in high-risk patients at W8. The study will be conducted in 2 parts. The phase I (Part A) is planned to include 6 patients. The phase II (Part B) will include 50 patients in two arms (25 patients respectively in the placebo and EXL01 arm)., conditionsModule conditions: Clostridioides Difficile Infection, conditions: Recurrent Infection, designModule studyType: INTERVENTIONAL, phases: PHASE1, phases: PHASE2, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: Part A = Single Arm open label. Part B = Randomised, placebo-controlled, double-blind., primaryPurpose: TREATMENT, maskingInfo masking: QUADRUPLE, maskingDescription: Part A: None (Open-label). Part B: Double-blind., whoMasked: PARTICIPANT, whoMasked: CARE_PROVIDER, whoMasked: INVESTIGATOR, whoMasked: OUTCOMES_ASSESSOR, enrollmentInfo count: 56, type: ESTIMATED, armsInterventionsModule interventions name: EXL01, interventions name: EXL01, interventions name: Placebo, outcomesModule primaryOutcomes measure: Incidence of Treatment-Emergent Adverse Events, primaryOutcomes measure: Evaluation of the efficacy of EXL01 in preventing recurrence of C. difficile infection in patients at high risk of recurrence, secondaryOutcomes measure: Evaluation of the efficacy of EXL01 in preventing recurrence of C. difficile infection in patients at high risk of recurrence, secondaryOutcomes measure: Evaluation of the safety and tolerability profile of oral EXL01, secondaryOutcomes measure: Number of stools per day over the past 24 hours, secondaryOutcomes measure: Stool consistency, as assessed by the Bristol scale, over the past 24 hours, secondaryOutcomes measure: Abdominal discomfort assessed by a validated irritable bowel syndrome scale, secondaryOutcomes measure: Number of stools per day over the past 24 hours, secondaryOutcomes measure: Stool consistency, as assessed by the Bristol scale, over the past 24 hours, secondaryOutcomes measure: Abdominal discomfort assessed by a validated irritable bowel syndrome scale, secondaryOutcomes measure: Assessment of patient quality of life during treatment and follow-up, secondaryOutcomes measure: Assessment of recurrence of C. difficile infection, secondaryOutcomes measure: Evaluation of the presence of EXL01 in the fecal microbiota, secondaryOutcomes measure: Assessment of EXL01 persistence in the intestinal microbiota, secondaryOutcomes measure: 16S rRNA sequencing or shotgun, secondaryOutcomes measure: 16S rRNA sequencing or shotgun, secondaryOutcomes measure: Assessment of the persistence of toxigenic C. difficile in the stool of patients in clinical remission during the study., secondaryOutcomes measure: Assessment of the persistence of toxigenic C. difficile in the stool of patients in clinical remission during the study., secondaryOutcomes measure: Assessment of recurrences of C. difficile infection requiring hospitalization, secondaryOutcomes measure: Assessment of recurrences of C. difficile infection requiring hospitalization, secondaryOutcomes measure: Assessment of recurrences of C. difficile infection requiring surgery, secondaryOutcomes measure: Assessment of recurrences of C. difficile infection requiring surgery, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Service d'hépato-gastroentérologie - CHU Estaing, city: Clermont-Ferrand, zip: 63003, country: France, contacts name: Julien SCANZI, MD, role: CONTACT, phone: 04 73 75 02 35, email: jscanzi@chu-clermontferrand.fr, contacts name: Julien SCANZI, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 45.77966, lon: 3.08628, locations facility: Service d'Hépato-gastroentérologie Hôpital de la Croix Rousse, city: Lyon, zip: 69004, country: France, contacts name: Nicolas BENECH, MD, role: CONTACT, phone: 04 26 10 94 35, phoneExt: +33, email: nicolas.benech@chu-lyon.fr, contacts name: Fanny JOUBERT, role: CONTACT, phone: 04 26 73 27 27, phoneExt: +33, email: Fanny.joubert@chu-lyon.fr, contacts name: Nicolas BENECH, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 45.74848, lon: 4.84669, locations facility: Service d'hépato-gastroentérologie - Hôpital Saint Antoine (APHP), city: Paris, zip: 75012, country: France, contacts name: Paul MCLELLAN, MD, role: CONTACT, phone: 01 49 28 20 00, phoneExt: +33, email: Paul.mclellan@aphp.fr, contacts name: Paul MCLELLAN, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 48.85341, lon: 2.3488, locations facility: Service d'infectiologie - Hôpital Nord / CHU Saint Etienne, city: Saint-Étienne, zip: 42100, country: France, contacts name: Elisabeth BOTHELO-NEVERS, Pr, role: CONTACT, phone: 04 77 12 77 89, phoneExt: +33, email: elisabeth.botelho-nevers@chu-st-etienne.fr, contacts name: Elisabeth BOTHELO-NEVERS, Pr, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 45.43389, lon: 4.39, locations facility: Service de médecine interne - Pôle des maladies de l'appareil digestif - CHU de Toulouse, city: Toulouse, zip: 31059, country: France, contacts name: Laurent ALRIC, Pr, role: CONTACT, phone: 05 61 32 37 54, email: Alric.l@chu-toulouse.fr, contacts name: Laurent ALRIC, Pr, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 43.60426, lon: 1.44367, locations facility: Service de Maladies Infectieuses - CH de Valence, city: Valence, zip: 26000, country: France, contacts name: Julien SAISON, MD, role: CONTACT, phone: 04 75 62 57 32, phoneExt: +33, email: jsaison@ch-valence.fr, contacts name: Julien SAISON, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 44.93333, lon: 4.9, hasResults: False