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Clostridioides Difficile InfectionPhase 1/2LIVEDIFFNCT06306014

Evaluation of EXL01, a New Live Biotherapeutic Product to Prevent Recurrence of Clostridioides Difficile Infection in High-risk Patients

A Phase 1/2 study testing EXL01 in people with Clostridioides Difficile Infection and Recurrent Infection, run by Hospices Civils de Lyon at 10 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
EXL01
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
56 participants
Where
10 sitesFrance
Study dates
7 May 2024to 7 Jan 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult patient ≥18 years of age
  • ≥3rd episode of proven C. difficile infection (≥3 liquid stools per day and detection of toxigenic C. difficile in stool by PCR or enzyme-linked immunosorbent assay or immunochromatography or toxigenic culture) within 6 months with an interval ≤ 12 weeks since the end of treatment of the previous episode of resolved CDI or 2nd episode of proven C. difficile infection (≥3 liquid stools per day and detection of toxigenic C. difficile in the stools by PCR or enzyme-linked immunosorbent assay or immunochromatography or toxigenic culture) within 6 months with an interval ≤ 12 weeks since the end of treatment of the previous episode of resolved CDI with at least one of the following risk factors:
  • Age ≥70 years
  • Chronic renal failure (haemodialysis or GFR<60ml/min
  • History of severe or severe-complicated CDI (excluding current episode) according to ESCMID 2021 criteria
  • ≥3 CDI in the last 12 months (including current episode)
Show all 10Show fewer
  • CDI associated with care defined as CDI occurring during hospitalisation (<3 months)
  • On current or planned vancomycin treatment per os
  • Patient able to give free, informed and written consent
  • Enrolled in compulsory national social security scheme

Who cannot join

  • Currently participating or has participated in a study with an investigational compound or device within 3 months prior to the first dose of the study intervention.
  • Severe C. difficile infection severe (defined by the presence of a white blood cell count >15×10⁹ cells/L or a body temperature >38.5°C or >50% increase in the patient's baseline creatinine related to CDI at the time of V1) and/or complicated (defined by any of the factors attributed to current Clostridioides difficile infection (CDI): hypotension, septic shock, elevated serum lactate, ileus, toxic megacolon, intestinal perforation or any fulminant course of the disease)
  • Refractory C. difficile infection defined as lack of response to well-conducted per os vancomycin or fidaxomicin treatment with ≥3 liquid stools per day after ≥5 days of treatment
  • Cirrhosis with Child C score
  • Hospitalization in continuing care unit or intensive care unit
  • Personal history of gastrointestinal resection other than appendectomy (gastrectomy, esophagectomy, colonic or small bowel resection, short small bowel syndrome).
Show all 26Show fewer
  • Personal history of gastrointestinal resection resulting in chronic diarrhea (>3 loose stools per day)
  • Inflammatory bowel disease
  • Proven uncontrolled celiac disease
  • Current stoma (ileostomy or colostomy) or within the last 6 months, or any other intra-abdominal surgery within the 3 months prior to treatment
  • major surgery or trauma ≤ 4 weeks before the start of treatment or, if > 4 weeks ago, with an unresolved healing process that could affect the assessment or safety of the study treatment.
  • Antibiotic therapy in progress or planned during the study for an infection other than CDI
  • Surgery scheduled during the study requiring perioperative antibiotics.
  • -Women without contraception*, pregnant or breastfeeding women
  • History of hypersensitivity to EXL01 and/or to any of its excipients (D-mannitol, sucrose, maltodextrin, L-cysteine, L-cysteine hydrochloride, magnesium stearate and hydroxypropylmethylcellulose), and/or to soy or soy-containing products.
  • History of hypersensitivity to vancomycin as mentioned in local prescribing information.
  • Personal history of fecal microbiota transplantation < 6 months
  • Persons deprived of liberty by judicial or administrative decision
  • Adults under legal protection or unable to give consent
  • Swallowing disorders making oral treatment impossible
  • Participation in another interventional study within 3 months prior to inclusion. (Patients who have entered the follow-up phase of an interventional study may participate provided that more than 3 months have elapsed since the last intervention).
  • Expected life expectancy of less than 6 months
  • Presents a known psychiatric disorder that would interfere with adequate cooperation with study requirements.
  • Regular use of illicit or recreational drugs that may interfere with the administration of the medication or the interpretation of the data
  • History of chronic diarrhea (> 3 watery stools per day for > 4 weeks) not related to gastrointestinal infection.
  • Clinically significant medical or surgical condition not mentioned in the above criteria which, in the opinion of the investigator, could interfere with the administration of study drug, the interpretation of study safety or efficacy data, or compromise the safety or well-being of the subject.

Trial locations and contacts

10 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Nicolas BENECH, MD contact

04 26 10 94 35 ext. +33

nicolas.benech@chu-lyon.fr

Fanny JOUBERT contact

04 26 73 27 27 ext. +33

Fanny.joubert@chu-lyon.fr

10 sites in 1 country

France10 sites, 10 recruiting

  • CH Annecy Genevois Service de Maladies infectieuses

    Annecy

    Emilie PIET, MD, 450636602 ext. +33, epiet@ch-annecygenevois.fr

    Emilie PIET, MD

    Not yet recruiting

  • Service d'hépato-gastroentérologie - CHU Estaing

    Clermont-Ferrand, 63003

    Julien SCANZI, MD, 04 73 75 02 35, jscanzi@chu-clermontferrand.fr

    Julien SCANZI, MD

    Recruiting

  • CHU Grenoble Service Maladies infectieuses et tropicales

    Grenoble

    Salomé GALLET, MD, 476763947 ext. +33, sgallet@chu-grenoble.fr

    Salomé GALLET, MD

    Recruiting

  • CHU Lille Unité des Maladies Infectieuses et tropicales

    Lille

    Sarah STABLER, MD, 320445743 ext. +33, sarah.stabler@chu-lille.fr

    Sarah STABLER, MD

    Recruiting

  • Service d'Hépato-gastroentérologie Hôpital de la Croix Rousse

    Lyon, 69004

    Nicolas BENECH, MD, 04 26 10 94 35 ext. +33, nicolas.benech@chu-lyon.fr

    Emma SANDOZ, 04 26 73 28 62 ext. +33, emma.sandoz@chu-lyon.fr

    Recruiting

  • APHM La Timone Service de Maladies infectieuses

    Marseille

    Nadim CASSIR, MD, nadimshams.cassir@ap-hm.fr

    Nadim CASSIR, MD

    Recruiting

  • Service d'hépato-gastroentérologie - Hôpital Saint Antoine (APHP)

    Paris, 75012

    Paul MCLELLAN, MD, 01 49 28 20 00 ext. +33, Paul.mclellan@aphp.fr

    Paul MCLELLAN, MD

    Recruiting

  • Service d'infectiologie - Hôpital Nord / CHU Saint Etienne

    Saint-Etienne, 42100

    Elisabeth BOTHELO-NEVERS, Pr, 04 77 12 77 89 ext. +33, elisabeth.botelho-nevers@chu-st-etienne.fr

    Elisabeth BOTHELO-NEVERS, Pr

    Recruiting

  • Service de médecine interne - Pôle des maladies de l'appareil digestif - CHU de Toulouse

    Toulouse, 31059

    Laurent ALRIC, Pr, 05 61 32 37 54, Alric.l@chu-toulouse.fr

    Laurent ALRIC, Pr

    Recruiting

  • Service de Maladies Infectieuses - CH de Valence

    Valence, 26000

    Amélie DUREAULT, MD, 04 75 75 75 71 ext. +33, adureault@ch-valence.fr

    Amélie DUREAULT, MD

    Recruiting

Other trials in France

About this study

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.

Read more

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).

Being tested
EXL01, Placebo
Keywords
Clostridioides difficile Infection, Live Biotherapeutic Product, Microbiota, Recurrent Infection
Medical subject headings
Clostridium Infections, Reinfection

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EXL01Drug

    Following a at least 10-days vancomycin treatment :

    Oral EXL01 including:

    • 10 capsules per day in week 1 and 2
    • 4 capsules per day, in weeks 3 and 4
    • 1 capsule per day in weeks 5 to 8 Phase I : EXL01 during a 8 weeks open-label period

  • EXL01Drug

    Following a at least 10-days vancomycin treatment :

    Oral EXL01 including:

    • 10 capsules per day in week 1 and 2
    • 4 capsules per day, in weeks 3 and 4
    • 1 capsule per day in weeks 5 to 8 Phase II: EXL01 during a 8 weeks double blind placebo-controlled period

  • PlaceboDrug

    Following a at least 10-days vancomycin treatment:

    Oral placebo including:

    • 10 capsules per day in week 1 and 2
    • 4 capsules per day, in weeks 3 and 4
    • 1 capsule per day in weeks 5 to 8 Phase II : Placebo during a 8 weeks double blind placebo-controlled period
Study groups in NCT06306014
Study groupRoleWhat they receive
Part A (Open-Label EXL01)ExperimentalNot described
Receives: Drug: EXL01
Part B (EXL01)ExperimentalNot described
Receives: Drug: EXL01
Part B (Placebo)Placebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Treatment-Emergent Adverse Events

    Phase I The primary endpoint is the occurrence of serious adverse events (CTCAE grade≥3) during treatment and follow-up and discontinuation of treatment due to adverse events attributed to treatment

    Measured: at Week 1, Week 2, Week 4, Week 8, Week 16

  2. Evaluation of the efficacy of EXL01 in preventing recurrence of C. difficile infection in patients at high risk of recurrence

    Phase II The primary endpoint is the proportion of patients at W8 after the start of treatment who had a recurrence of toxigenic C. difficile defined by ≥3 liquid stools per day for more than 48 hours + detection of C. difficile toxin in stool (enzyme-linked immunosorbent assay or toxigenic culture +/- PCR) resulting in the initiation of CDI-specific treatment.

    Measured: at Week 8

Secondary outcomes (20)

  1. Evaluation of the efficacy of EXL01 in preventing recurrence of C. difficile infection in patients at high risk of recurrence

    Phase I Proportion of patients at W8 after the start of treatment who had a recurrence of toxigenic C. difficile defined by ≥3 liquid stools per day for more than 48 hours + detection of C. difficile toxin in stool (enzyme-linked immunosorbent assay or toxigenic culture +/- PCR) resulting in the initiation of specific treatment for CDI.

    Measured: at Week 8

  2. Evaluation of the safety and tolerability profile of oral EXL01

    Phase II Occurrence of adverse events (CTCAE grade≥3) during treatment and follow-up, and discontinuation of treatment due to adverse events

    Measured: at Week 2, Week 4, Week 8, Week 16

  3. Number of stools per day over the past 24 hours

    Phase I Assessment of digestive symptoms during treatment and follow-up Digestive symptoms are measured at each visit using a stool calendar

    Measured: at Week 0, Week 1, Week 2, Week 4, Week 8, Week 16

  4. Stool consistency, as assessed by the Bristol scale, over the past 24 hours

    Phase I Digestive symptoms are measured at each visit using the stool calendar

    Measured: at Week 0, Week 1, Week 2, Week 4, Week 8, Week 16

  5. Abdominal discomfort assessed by a validated irritable bowel syndrome scale

    Phase I Assessment of digestive symptoms during treatment and follow-up Digestive symptoms are measured at each visit (IBS-SSS modified, GCSI, GERDQ)

    Measured: at Week 8, Week 16

  6. Number of stools per day over the past 24 hours

    Phase II Assessment of digestive symptoms during treatment and follow-up Digestive symptoms are measured at each visit using a stool calendar

    Measured: at Week 0, Week 2, Week 4, Week 8, Week 16

  7. Stool consistency, as assessed by the Bristol scale, over the past 24 hours

    Phase II Digestive symptoms are measured at each visit using the stool calendar

    Measured: at Week 0, Week 2, Week 4, Week 8, Week 16

  8. Abdominal discomfort assessed by a validated irritable bowel syndrome scale

    Phase II Assessment of digestive symptoms during treatment and follow-up Digestive symptoms are measured at each visit (IBS-SSS modified, GCSI, GERDQ)

    Measured: at Week 8, Week 16

  9. Assessment of patient quality of life during treatment and follow-up

    Phases I and II Patient quality of life at W8 and M4 measured by a validated digestive disease quality of life questionnaire (GIQLI)

    Measured: At Week 8 and Week 16

  10. Assessment of recurrence of C. difficile infection

    Phases I and II percentage of patients with recurrence of C. difficile infection at M4

    Measured: At Week 16

  11. Evaluation of the presence of EXL01 in the fecal microbiota

    Phases I and II Level of F. prausnitzii (qPCR) in stool at W8 versus W0

    Measured: At Week 8

  12. Assessment of EXL01 persistence in the intestinal microbiota

    Phases I and II Level of F. prausnitzii (qPCR) in stool at M4 versus W0

    Measured: At Week 0 and Week 16

  13. 16S rRNA sequencing or shotgun

    Phase I Gut microbiota composition at each visit

    Measured: at Week 0, Week 1, Week 2, Week 4, Week 8, Week 16

  14. 16S rRNA sequencing or shotgun

    Phase II Gut microbiota composition at each visit

    Measured: at Week 0, Week 2, Week 4, Week 8, Week 16

  15. Assessment of the persistence of toxigenic C. difficile in the stool of patients in clinical remission during the study.

    Phase I Percentage of patients at each visit with a positive stool PCR test for toxigenic C. difficile considered to be in clinical remission

    Measured: at Week 0, Week 1, Week 2, Week 4, Week 8, Week 16

  16. Assessment of the persistence of toxigenic C. difficile in the stool of patients in clinical remission during the study.

    Phase II Percentage of patients at each visit with a positive stool PCR test for toxigenic C. difficile considered to be in clinical remission

    Measured: at Week 0, Week 2, Week 4, Week 8, Week 16

  17. Assessment of recurrences of C. difficile infection requiring hospitalization

    phases I and II percentage of patients with recurrence of C. difficile infection requiring hospitalization at W8

    Measured: At Week 8

  18. Assessment of recurrences of C. difficile infection requiring hospitalization

    phases I and II percentage of patients with recurrence of C. difficile infection requiring hospitalization at M4

    Measured: at Week 16

  19. Assessment of recurrences of C. difficile infection requiring surgery

    phases I and II phases I and II percentage of patients with a recurrence of C. difficile infection requiring surgery at W8

    Measured: at Week 8

  20. Assessment of recurrences of C. difficile infection requiring surgery

    phases I and II percentage of patients with recurrent C. difficile infection requiring surgery at M4

    Measured: at Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2024
  2. Study start7 May 2024
  3. Primary completion7 Jan 2028 (estimated)
  4. Study completion7 Jan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Part A = Single Arm open label. Part B = Randomised, placebo-controlled, double-blind.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
56 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06306014
Sponsor's protocol ID
69HCL22_0980
Other IDs
2023-506232-32-00, 2023
Acronym
LIVEDIFF
Status last verified
Oct 2026
First submitted
21 Feb 2024
Last updated
20 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Benech N, Guarino-Vignon P, McLellan P, Campidelli C, Sergeant M, Joubert F, Truong S, Barbier P, Sandoz E, Ruffie P, Sedda D, Delmeule A, Pradat P, Landman C, Bourrier A, Marchand L, Alric L, Scanzi J, Cassir N, Dureault A, Piet E, Gallet S, Botelho-Nevers E, Roussel-Gaillard T, Cuerq C, Ader F, Guillet M, Rolhion N, Grill JP, Lamaziere A, Chatel JM, Pechine S, Langella P, Sokol H. Faecalibacterium prausnitzii EXL01 Strain for the prevention of multiple-recurrent Clostridioides difficile Infection. Gastroenterology. 2026 Sep 17:S0016-5085(26)07249-5. doi: 10.1053/j.gastro.2026.09.002. Online ahead of print.

    PubMed 42753987

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing EXL01 in people with Clostridioides Difficile Infection and Recurrent Infection, run by Hospices Civils de Lyon at 10 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Nicolas BENECH, MD (04 26 10 94 35 ext. +33, nicolas.benech@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Treatment-Emergent Adverse Events (time frame: at Week 1, Week 2, Week 4, Week 8, Week 16). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06306014, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026.

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