Safety and Efficacy Study of Gynevac Lactobacillus Vaccine in the Treatment of Bacterial Vaginosis

Study Overview
=================
Brief Summary
-----------------
To investigate the efficacy (therapeutic response) of Gynevac vaccination following a 5-shot treatment period in patients with bacterial vaginosis, based on the Nugent Score and the Amsel criteria

Official Title
-----------------
Phase III, Randomized, Double Blind, Parallel Groups, Placebo Controlled Clinical Study to Evaluate the Efficacy and Safety of the Lactobacillus Vaccine Gynevac, in the Treatment of Bacterial Vaginosis

Conditions
-----------------
Bacterial Vaginosis

Intervention / Treatment
-----------------
* Biological: Gynevac
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult premenopausal females, 18 years and older. Mentally competent patients that can comply with the study protocol and are able to complete and keep or study related material (patient diaries, etc.). Signed and dated written informed consent. Clinical diagnosis of BV according to Amsel criteria Gram stains Nugent Score ≥7 or Nugent Score 4-6 with the presence of clue cells Patient does not need an anti-infective treatment which would be required for specific treatment of vaginosis or to prevent the development of acute vaginitis and which may affect treatment outcome of BV. Negative pregnancy test at screening. Exclusion Criteria: Patients with other infectious causes of vulvovaginitis (e.g. Vaginal candidiasis, Trichomonas vaginalis). Patients with another vaginal or vulvar condition, which would confound the interpretation of clinical and or therapeutic response. Patients who received antifungal or antimicrobial therapy (systemic or intravaginal), as part of standard clinical practice, or clinical trial, within 14 days of randomization. Patients who are diagnosed with a chronic inflammatory disease (Rheumatoid Arthritis, psoriasis, Crohn's disease, Coeliac disease, spondyloarthritis rheumatica etc.) Women who are scheduled to be under treatment during the study period for cervical intraepithelial neoplasia (CIN) or cervical carcinoma. Pregnancy or lactation. Patients with known hypersensitivity to formaldehyde. Patients undergoing antibiotic treatment. Patients with acute polyarthritis, known serious cardiac, liver, kidney diseases or unstable diabetes mellitus. Known abnormalities of the blood circulation or of the haemopoietic system. Use of any investigational drug within 30 days from randomization. Patients who do not abstain from use of intravaginal products for at least 7 days prior to study randomization (e.g. douches, female deodorant sprays, spermicides, condoms, tampons, and diaphragms). Patients should also refrain from using intravaginal products 3 days prior to each study visit. Patients who do not abstain from vaginal intercourse during at least 3 days prior to each study visit.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo vehicle (0.9% NaCl solution) | Biological: Placebo<br>* 1 IM injection of Placebo per week, for 4 weeks (five injections in total). Vaccination can take place in no less than 7 days intervals (+3 days).<br>|
| Experimental: Gynevac<br>Gynevac suspension for injection, a vaccine containing Lactobacillus strains 15, 34, 79, 84, 127 inactivated by formaldehyde in 0.9% NaCl solution | Biological: Gynevac<br>* 1 IM injection of Gynevac per week, for 4 weeks (five injections in total). Vaccination can take place in no less than 7 days intervals (+3 days).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic response | The percentage of patients with remission according to Amsel's criteria at week 7: resolution of the clinical findings assessed at baseline, and remission according to Gram stain Nugent score: score < 4 or 4 to 6 with no presence of clue cells at week 7. | 3 weeks from the time of last vaccine administration (+3 days maximum) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance of BV infection according to Amsel criteria | The percentage of patients with clearance of infection according to Amsel criteria response (three of four from: physiological discharge, negative Whiff test, negative saline wet mount for clue cells and pH<4.7) in Gynevac® or placebo, at week 7. | 3 weeks from the time of last vaccine administration (+3 days maximum) | 
| Clearance of BV infection according to Nugent Score | The percentage of patients with clearance of infection according to Nugent Score (NS <4 or 4-6 with no presence of clue cells) in Gynevac® or placebo, at week 7. | 3 weeks from the time of last vaccine administration (+3 days maximum) | 
| Overall therapeutic failure | Percentage of patients whose overall therapeutic outcome is failure, defined as Amsel = cure and Nugent score ≥4 with the presence of clue cells and Amsel = failure regardless of Nugent Score, week 7. | 3 weeks from the time of last vaccine administration (+3 days maximum) | 
| Change in Nugent Score | Median difference between Gynevac or placebo of the change in Nugent Score from baseline to week 7. | 3 weeks from the time of last vaccine administration (+3 days maximum) | 
| Change in pre- and post-vaccination IgA, IL17, and IFNγ | Median difference from baseline of IgA, IL17 and IFNγ in PBMCs isolated on week 7 by participants treated with Gynevac or Placebo | 3 weeks from the time of last vaccine administration (+3 days maximum) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
bacterial vaginosis, Gynevac Lactobacillus vaccine