Study of the Efficacy and Tolerance of Intra-vaginal Treatment With a Total Freeze-dried Culture of Lcr Regenerans® in the Prevention of Relapses of Recurrent Vulvovaginal Candidiasis

Phase

Condition

Gynecological Infections

Systemic Fungal Infections

Yeast Infections

Treatment

N/A

Clinical Study ID

NCT02251093

PRO_2013 - 02

2013-002480-26

Female

Study Summary

The trial medicinal product (Lcr Regenerans®) is obtained from the culture of a strain of Lactobacillus rhamnosus Lcr35®. By virtue of the freeze-drying technique, Lactobacillus rhamnosus Lcr35® is a live bacterium administered with its culture medium.

It should be noted that Lcr Regenerans® is already marketed as a medical device (EC marking: 0499). It helps to regenerate the vaginal flora thanks to its physical and chemical effects (lowering the vaginal pH).

A number of in vitro and in vivo studies have demonstrated the ability of Lactobacillus rhamnosus Lcr35®:

to establish itself in the vaginal epithelium, along with the durability of this establishment.
and to inhibit the growth of pathogenic organisms responsible for causing bacterial vaginosis (Gardnerella vaginalis and Prevotella bivia) but also for mycoses (Candida albicans), by synthesising various microbicidal substances.

This research follows on from the Candiflore observational study in which 514 patients were monitored and which demonstrated a clearly positive result in favour of the use of vaginal Lcr Regenerans® for preventing recurrences of VVC.

The purpose of this new research is thus to demonstrate the efficacy of Lcr Regenerans®, in the prevention of vulvovaginal candidiasis recurrences in patients with a history of VVC with recurrent episodes, in view of obtaining a marketing authorisation.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Patient suffering from recurrent VVC (RVVC) defined by the existence of at least 4 VVCepisodes during the past year, including the one concerned by the screening visit Inaddition to the current episode, at least one episode occurring during the twoprevious years must also have been documented by mycological examination
Patient suffering from acute vulvovaginitis characterised by the presence of thefollowing clinical criteria at V1 (pruritus symptoms, vulvovaginal signs such aserythema, vaginal discharge)
Patient with a positive mycological examination at V1
Patient cured in clinical terms 8 days after treatment with MONAZOL 300 mg vaginalsuppositories (one suppository at night before sleep, single administration) andfollowed by the application of MONAZOL 2 pourcent cream (8-day treatment)
Woman of child-bearing age with a negative urine pregnancy test and using a means ofcontraception deemed effective by the investigator (excluding spermicides) throughoutthe trial
Patient/Legal representative able to speak and read the local language, having beeninformed of the trial and having voluntarily signed an Informed Consent Form
Patient/Legal representative registered with a social insurance scheme

Exclusion

Exclusion Criteria:

Presence of a presumed or proven, gynaecologically-related bacterial or viralinfection, whether treated or not during the month preceding the inclusion, or presentat the time of inclusion.
Presence of an existing gynaecological infection that could interfere with theassessment of the trial treatment (severe cervical dysplasia or carcinoma in situ,invasive carcinoma, intra-epithelial cervical neoplasia, squamous intra-epitheliallesions etc.)
Patients with a negative mycological examination at V1
Lack of adequately documented previous episodes to assert the recurrent nature of theVVC (4 episodes in one year, two of which documented by mycological examination overthe past two years [thus, in addition to the current episode, at least one episodeoccurring during the two previous years must also have been documented by mycologicalexamination])
Antifungals taken by general route (in particular Fluconazole) during the monthpreceding the screening visit, in view of preventing recurrences (the treatment of anacute VVC episode is not an exclusion criterion).
Use of probiotics in the month preceding the screening visit.
Use of prebiotics (acidifiers) during the two weeks preceding the screening visit.
Allergy to one of the active ingredients or one of the excipients in the products.
Patient unable to comply with the constraints of the Protocol.
Breastfeeding patient.
Patient with menstrual bleeding lasting more than 8 days a month.
Post-menopausal women with last menstrual period at least 12 months prior to screening
Patient having taken part in a clinical trial in the 3 months preceding inclusion inthe present Protocol.
Patient with a severe acute or chronic disease deemed by the Investigator to beincompatible with participation in the trial, or a serious infection that islife-threatening in the short term.
Immuno-suppressed patient.
Patient presenting with a previous illness which, according to the Investigator, islikely to interfere with the results of the trial or expose the patient to anadditional risk.
Patient linguistically (unable to speak or write the local language) or mentallyunable to understand and sign the Informed Consent Form.
Patient deprived of her liberty by order of the Courts or civil authorities or subjectto a guardianship order.
Patient likely not to comply with treatment.
Patient unable to be contacted in the case of an emergency.

Study Design

May 01, 2014

Study Description

Treatment of RVVC is difficult due to the multi-factor nature of recurrences and of the poorly understood local immune dysfunctions that may arise. The oral or topical antifungal maintenance treatment usually recommended is for a period of 6 months, though the VVC relapse rate is high, with 60 to 70% of women presenting with a recurrence within 2 months following termination of treatment. Moreover, antifungal agent-related adverse events are frequent and their long-term use can be conducive to the onset of bacterial vaginosis (BV).

The vaginal administration of probiotic strains (Lactobacillus) capable of regenerating the vaginal flora and of inhibiting the development of Candida albicans and/or its adhesion to the vaginal epithelium, would appear to be an interesting therapeutic alternative for preventing VVC recurrences.