Clinical trial NCT02251093: 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
Official title: 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. International Phase III, Randomised, Multi-centre, Parallel-group, Two Arm, Double-blind Superiority Trial Versus Placebo.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Candidiasis, Vulvovaginal
Keywords: mycosis
vulvovaginal candidiasis
lcr35
Lcr Regenerans®
Lead sponsor: Probionov
Sponsor class: INDUSTRY
First posted: 2014-09-26
Enrollment: 350
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

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 Criteria:

* Patient suffering from recurrent VVC (RVVC) defined by the existence of at least 4 VVC episodes during the past year, including the one concerned by the screening visit In addition to the current episode, at least one episode occurring during the two previous years must also have been documented by mycological examination
* Patient suffering from acute vulvovaginitis characterised by the presence of the following clinical criteria at V1 (pruritus symptoms, vulvovaginal signs such as erythema, vaginal discharge)
* Patient with a positive mycological examination at V1
* Patient cured in clinical terms 8 days after treatment with MONAZOL 300 mg vaginal suppositories (one suppository at night before sleep, single administration) and followed 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 of contraception deemed effective by the investigator (excluding spermicides) throughout the trial
* Patient/Legal representative able to speak and read the local language, having been informed of the trial and having voluntarily signed an Informed Consent Form
* Patient/Legal representative registered with a social insurance scheme

Exclusion Criteria:

* Presence of a presumed or proven, gynaecologically-related bacterial or viral infection, whether treated or not during the month preceding the inclusion, or present at the time of inclusion.
* Presence of an existing gynaecological infection that could interfere with the assessment of the trial treatment (severe cervical dysplasia or carcinoma in situ, invasive carcinoma, intra-epithelial cervical neoplasia, squamous intra-epithelial lesions etc.)
* Patients with a negative mycological examination at V1
* Lack of adequately documented previous episodes to assert the recurrent nature of the VVC (4 episodes in one year, two of which documented by mycological examination over the past two years \[thus, in addition to the current episode, at least one episode occurring during the two previous years must also have been documented by mycological examination\])
* Antifungals taken by general route (in particular Fluconazole) during the month preceding the screening visit, in view of preventing recurrences (the treatment of an acute 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 in the present Protocol.
* Patient with a severe acute or chronic disease deemed by the Investigator to be incompatible with participation in the trial, or a serious infection that is life-threatening in the short term.
* Immuno-suppressed patient.
* Patient presenting with a previous illness which, according to the Investigator, is likely to interfere with the results of the trial or expose the patient to an additional risk.
* Patient linguistically (unable to speak or write the local language) or mentally unable to understand and sign the Informed Consent Form.
* Patient deprived of her liberty by order of the Courts or civil authorities or subject to a guardianship order.
* Patient likely not to comply with treatment.
* Patient unable to be contacted in the case of an emergency.

Primary outcomes:
measure: Recurrence confirmed by a mycological test, occurring during the treatment period, or within 5 months of trial treatment termination
timeFrame: 5 months
Secondary outcomes:
Other outcomes:
Locations:
city: Aurillac
country: France
facility: Probionov
Study officials:
affiliation: Maternité Régionale Universitaire de Nancy
name: Philippe JUDLIN
role: PRINCIPAL_INVESTIGATOR
References: