Evaluation of EXL01 a new Live Biotherapeutic Product to prevent recurrence of Clostridioides difficile infection in high-risk patients. LIVEDIFF

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospices Civils De Lyon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

8 Apr 2024 → ongoing

Decision date (initial)

2023-11-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS · Exeliom Biosciences

External identifiers

EU CT number

2023-506232-32-00

ClinicalTrials.gov

NCT06306014

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Phase I: Evaluation of the safety and tolerability of oral EXL01
Phase II: Evaluation of the efficacy of EXL01 in preventing recurrence of C. difficile infection at S8 in patients at high risk of recurrence

Secondary objectives 13

1. Phase I: Evaluation of the efficacy of EXL01 in preventing recurrence of C. difficile infection at S8 in patients at high risk of recurrence
2. Phase II: Evaluation of the safety and tolerability profile of oral EXL01
3. Assessment of digestive symptoms during treatment and follow-up
4. Assessment of the patient's quality of life during treatment and follow-up
5. Assessment of recurrence of C. difficile infection at M4
6. Assessment of the presence of EXL01 in the faecal microbiota at S8
7. Assessment of the persistence of EXL01 in the intestinal microbiota at M4
8. Assessment of the composition of the intestinal microbiota as a whole during treatment.
9. Assessment of the persistence of toxigenic C. difficile in the faeces of patients in clinical remission during the study.
10. Assessment of recurrence of C. difficile infection requiring hospitalisation at S8
11. Assessment of recurrences of C. difficile infection requiring hospitalisation at M4
12. Assessment of recurrences of C. difficile infection requiring surgery at S8
13. Evaluation of recurrences of C. difficile infection requiring surgery at M4

Conditions and MedDRA coding

Multiple recurrences of Clostridioides difficile infection treated with oral Vancomycin

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patient over 18 years of age
2. 3rd 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 or 2nd episode of proven C. difficile infection (≥3 liquid stools per day and detection of toxigenic C. difficile in the 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 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 episodes of CDI in the last 12 months (including the current episode) - Care-associated CDI defined as CDI occurring during hospitalisation (<3 months)
3. On current or planned vancomycin treatment per os
4. Patient capable of giving free, informed and written consent
5. Enrolled in the national compulsory social security scheme

Exclusion criteria 26

1. Currently participating or has participated in a study with an investigational compound or device in the 3 months prior to the first dose of the study intervention.
2. Chronic inflammatory bowel disease
3. Personal history of gastrointestinal resection resulting in chronic diarrhea (>3 loose stools per day)
4. Personal history of microbial overgrowth of the small intestine
5. Hospitalisation in a continuing care unit or intensive care unit
6. Proven uncontrolled celiac disease
7. Current stoma (ileostomy or colostomy) or within the last 6 months or any other intra-abdominal surgery within the 3 months prior to treatment
8. Swallowing disorders making it impossible to take oral treatment
9. major surgery or trauma ≤ 4 weeks before the start of treatment or if > 4 weeks with an unresolved healing process that could affect the assessment or safety of the study treatment.
10. Surgery scheduled during the study requiring perioperative antibiotics.
11. Antibiotic treatment in progress or planned during the study for an infection other than CDI
12. History of chronic diarrhoea (> 3 liquid stools per day for > 4 weeks) not related to a gastrointestinal infection.
13. 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 the study drug, the interpretation of the study safety or efficacy data, or compromise the safety or well-being of the subject.
14. Women without contraception, pregnant or breast-feeding women
15. History of hypersensitivity to EXL01 and/or to any excipient with a known effect (D-mannitol, sucrose, maltodextrin, L-cysteine, L-cysteine hydrochloride, magnesium stearate and hydroxypropylmethylcellulose), and/or soya or products containing soya.
16. History of hypersensitivity to vancomycin mentioned in the local prescribing information.
17. Personal history of faecal microbiota transplantation < 6 months.
18. Participation in another interventional studY. (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.)
19. Person deprived of liberty by a judicial or administrative decision
20. Adults subject to a legal protection measure or unable to express their consent
21. Refractory C. difficile infection defined as lack of response to adequate treatment with oral vancomycin or fidaxomicin with ≥3 liquid stools per day after ≥5 days of treatment
22. 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) Translated with DeepL.com (free version)
23. Expected life expectancy of less than 6 months
24. Presents a known psychiatric disorder that would interfere with adequate cooperation with the study requirements.
25. Regular use of illicit or recreational drugs that may interfere with medication administration or data interpretation
26. Cirrhosis with Child C score

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Phase I: Occurrence of serious adverse events (CTCAE grade≥3) during treatment and follow-up and discontinuation due to adverse events attributed to treatment. Phase II: Proportion of patients at S8 after the start of treatment who had a recurrence of toxigenic C. difficile defined as ≥3 loose 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.

Secondary endpoints 13

1. Phase I: Proportion of patients at S8 after the start of treatment who had a recurrence of toxigenic C. difficile defined as ≥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.
2. Phase II: Occurrence of adverse events (CTCAE grade≥3) during treatment and follow-up and discontinuation of treatment due to adverse events
3. Digestive symptoms are measured at each visit by : o The number of bowel movements per day over the last 24 hours, using the stool calendar o Stool consistency assessed using the Bristol scale over the last 24 hours using the stool calendar o Abdominal discomfort assessed by a validated irritable bowel syndrome scale (IBS-SSS) at S8 and M4
4. Patient quality of life at S8 and M4 measured by a quality of life questionnaire validated in digestive diseases (IBS-QOL)
5. percentage of patients with a recurrence of C. difficile infection at M4
6. Level of F. prausnitzii (qPCR) in stools at S8 versus S0
7. Level of F. prausnitzii (qPCR) in faeces at M4 versus S0
8. Composition of intestinal microbiota (determined by 16S rRNA sequencing or shotgun) at each visit
9. percentage of patients at each visit with a positive fecal toxigenic C. difficile test (PCR) and considered to be in clinical remission
10. percentage of patients with a recurrence of C. difficile infection requiring hospitalisation at S8
11. percentage of patients with a recurrence of C. difficile infection requiring hospitalisation at M4
12. percentage of patients with a recurrence of C. difficile infection requiring surgery at S8
13. percentage of patients with a recurrence of C. difficile infection requiring surgery at M4

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospices Civils De Lyon

Sponsor organisation

Hospices Civils De Lyon

Address

3 Quai Des Celestins, Bp 2251 Bp 2251

City

Lyon Cedex 02

Postcode

69229

Country

France

Scientific contact point

Organisation

Hospices Civils De Lyon

Contact name

Dr Nicolas BENECH

Public contact point

Organisation

Hospices Civils De Lyon

Contact name

Dr Nicolas BENECH

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications