Effect of Saccharomyces boulardii CNCM I-745 on gut microbiota in patients undergoing antibiotic therapy (in the context of erythema migrans (early skin form of Lyme borreliosis) - SUBLYME

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biocodex

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

18 Jun 2024 → ongoing

Decision date (initial)

2025-07-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Prophylaxis

To assess the effect of Saccharomyces boulardii CNCM I-745, an antibiotic, and their combination on the gut microbiota of patients receiving antibiotic (in the context of erythema migrans)

Secondary objectives 4

1. To assess the efficacy of Saccharomyces boulardii CNCM I-745 in prevention of antibiotic-associated diarrhoea (AAD) in patients undergoing antibiotic therapy (in the context of erythema migrans).
2. To assess the efficacy of Saccharomyces boulardii CNCM I-745 on the stools in patients undergoing antibiotic therapy (in the context of erythema migrans).
3. To assess the effect of Saccharomyces boulardii CNCM I-745, an antibiotic, and their combination on the gut resistome of patients receiving antibiotic (in the context of erythema migrans).
4. To assess the safety and tolerability of Saccharomyces boulardii CNCM I-745

Conditions and MedDRA coding

Patients undergoing antibiotic therapy (in the context of erythema migrans (early skin form of Lyme borreliosis))

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Adult Patients, ≥18 years old
2. Who were prescribed antibiotic therapy (as per medical routine practices, amoxicillin 1000 mg bid for 14 days) in the context of erythema migrans (early skin form of Lyme borreliosis).
3. Able to comply with study requirements and to provide signed informed consent before any study procedure.
4. Has no condition that may interfere with the study assessments.
5. Able to fulfil in the diary stool log, according to the physician’s opinion.
6. Regular defecation (frequency and stool consistency, with at least about three bowel movements a week).
7. For women of childbearing potential: -A negative urine pregnancy test immediately prior to starting the study treatment, -Agreement to comply with approved methods of contraception during the whole study: unless they meet the criteria of post-menopausal, i.e. 12 months of spontaneous amenorrhea, women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner, should use one or more acceptable methods of contraception that should be maintained throughout the study)

Exclusion criteria 20

1. History of hypersensitivity to the study treatments (active substance or excipients), brewer’s or baker’s yeast
2. Contraindication and special warning to the study drugs according to the SmPCs
3. History of chronic constipation with passage of fewer than 3 spontaneous bowel movements per week on average
4. History of chronic or recurrent diarrhoea with spontaneous unformed bowel movements equivalent to or more often than 3 times daily
5. Prior gastrointestinal surgery (apart from appendectomy or cholecystectomy performed at least more than one year ago)
6. History of Clostridium difficile infection
7. Active gastrointestinal inflammatory disease
8. Known chronic or recurrent systemic disorder that may interfere with the study drug evaluation
9. Immunocompromised (organtransplants, leukaemia, malignant tumours, radiotherapy, chemotherapy,prolonged high dose cortisone treatment, immunosuppressant treament) or critically ill patients (such as autoimmune disease, HIV,…), patients with a central venous catheter
10. Severe hepatic or renal impairment
11. Systemic antibacterial therapy during the 2 months prior to study enrollment
12. New prescription medications during the 2 weeks prior to study enrollment
13. AUse of any drug or product that alters gut microbiota or function, such as probiotics, laxatives, antiemetics, cisapride, antisecretory or adsorbent treatments (racecadotril, smectite, activated charcoal), opiates such as loperamide, atropine and other cholinergic agents, during 4 weeks prior to study enrollment and during the study
14. Intake of antifungals within 14 days prior to study enrollment
15. Substantial changes in eating habits within 30 days prior to receiving the first dose of IMP product, and during the study as assessed by the Investigator
16. History or presence of drug or alcohol abuse
17. Heavy smoker (more than 10 cigarettes per day)
18. Breast-feeding woman
19. Patients enrolled in another interventional clinical trial where they received an investigation treatment within the past 30 days
20. Any condition or personal circumstance that, in the opinion of the investigator, rendered the subject unlikely or unable to comply with the full study protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Changes observed: - in bacterial and fungal taxonomy (alpha diversity, Shanon index) - in beta diversity metrics (such as Bray Curtis dissimilarity, Jaccard distance, Unifrac...). Analyses will be performed by treatment group and at each assessment time.

Secondary endpoints 5

1. Incidence of AAD (The number of AAD episodes that occurred during the treatment period) will be assessed using the Bristol Stool Form Scale (BSFS) recorded daily. Analyses will be performed by treatment group
2. The proportion of patients with at least one AAD episode will be compared between the two treatment groups
3. Time frame in hours up to the time of the last liquid or loose stool (defined as types 6 or 7 on BSFS) followed by the first 24-hour period with stool consistency improvement (no liquid or loose stool), as recorded by the patients in the stool diary or as collected by the investigator, the average number of stools per week, the average number of unformed or formed (according to the score) stools per week, duration of number of days with diarrhea, number of episodes of diarrhea.
4. Changes from baseline of the GSRS score (total score) and diarrhea sub-scores will be compared weekly between the treatment groups.
5. Safety will be evaluated based on recorded adverse events (number of events and number of participants with at least one event), vital signs, and physical examination (quantitative statistics at each assessment time and changes from baseline).

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biocodex

Sponsor organisation

Biocodex

Address

22 Rue Des Aqueducs

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Biocodex

Contact name

Dounia HOUAMEL

Public contact point

Organisation

Biocodex

Contact name

Gaëlle MARIAULE

Third parties 4

Locations

4 EU/EEA countries · 18 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 25 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