Safety and Efficacy of 5% Monolaurin Vaginal Gel Administered Intravaginally for the Treatment of Bacterial Vaginosis

Study Overview
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Brief Summary
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This is a Phase II, Double-Blind, Randomized, Placebo-Controlled, Multi-center Trial enrolling 120 subjects with Bacterial Vaginosis who will be randomized at a ratio of 2:1 to receive active test article (5% Monolaurin Vaginal Gel) or placebo (vehicle). The primary objective is to assess the safety and tolerability of 5% Monolaurin Vaginal Gel compared to vehicle placebo gel (excipients only) and to assess the efficacy by clinical cure rate of 5% Monolaurin Vaginal Gel compared to vehicle placebo gel at Visit 2.

Detailed Description
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Bacterial vaginosis (BV) is a disease of the vagina caused by bacteria. The most common symptom of BV is an abnormal homogeneous off-white vaginal discharge (especially after sex) with an unpleasant smell. This is a Phase II, Double-Blind, Randomized, Placebo-Controlled, Multi-center Trial enrolling 120 women, 18-50 years old, with clinical evidence of bacterial vaginosis. Subjects will be randomized at a ratio of 2:1 to receive active test article (5% Monolaurin Vaginal Gel) or placebo (vehicle) as outpatient therapy. Subjects will be stratified by first time episode of bacterial vaginosis or recurrent bacterial vaginosis. The primary objectives of this study are: 1) To assess the safety and tolerability of 5% Monolaurin Vaginal Gel compared to Vehicle Placebo Gel (excipients only) and 2) To assess the efficacy by clinical cure rate of 5% Monolaurin Vaginal Gel compared to Vehicle Placebo Gel at Visit 2. The secondary objectives are : 1) To evaluate the therapeutic cure rate of 5% Monolaurin Vaginal Gel compared to Vehicle Placebo Gel at Visits 2 and 3, 2) To evaluate the clinical cure rate of 5% Monolaurin Vaginal Gel compared to Vehicle Placebo Gel at Visit 3, 3) To evaluate the changes in Nugent's criteria of vaginal bacterial flora at Visits 2 and 3. This study is expected to last for 13 months, with subject participation duration being 4 weeks.

Official Title
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A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial to Assess the Safety and Efficacy of 5% Monolaurin Vaginal Gel Administered Intravaginally for the Treatment of Bacterial Vaginosis

Conditions
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Bacterial Vaginosis

Intervention / Treatment
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* Drug: 5% Monolaurin Vaginal Gel
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-pregnant, non-breastfeeding females between the ages of 18 and 50 years, inclusive Women of childbearing potential* must agree to practice reliable contraception** for the 28-day period before enrollment through 30 days following treatment. *(not surgically sterile via tubal ligation, bilateral oophorectomy or hysterectomy, or who have not been postmenopausal for >/=1 year) ** Acceptable birth control methods for the purposes of this study may include, but are not limited to, abstinence from intercourse with a male partner, monogamous relationship with vasectomized partner, barrier methods to include condoms and diaphragms, intrauterine devices, and licensed hormonal methods. NuvaRing® contraceptive use will be prohibited from this study since the device can alter vaginal secretions Presenting with signs of BV (as per Amsel Criteria). Subjects must meet any three of the four criteria for enrollment* *Presence of discharge, greater than or equal to 20% clue cells on wet prep, positive whiff test on KOH prep, vaginal pH of greater than 4.5 Not currently menstruating or expected to in the next 4 days Able to understand and comply with planned study procedures Willing to abstain from sexual intercourse, insertion of tampons, douches, or other intravaginal medications or objects between Visit 1 and Visit 2 and 48 hours prior to Visit 3 Provide written informed consent before initiation of any study procedures and be available for all study visits No known history of HIV Exclusion Criteria: -Signs or symptoms of vaginal/cervical/pelvic infection on screening or clinical diagnosis of vaginal/cervical/pelvic infection in the past 14 days. (including but not limited to yeast vulvovaginitis, chlamydia, gonorrhea, trichomonas, genital ulcer disease, pelvic inflammatory disease). Self-treatment for presumed yeast vaginitis is not an exclusion if treatment was discontinued 7 days or greater prior to enrollment Treatment for BV within the past 14 days Cervical or vaginal high grade squamous intraepithelial dysplasia (HSIL), atypical glandular cells of uncertain significance (AGUS) or cervical intraepithelial neoplasia grade 2 (CIN2) or higher* Atypical squamous cells of undetermined significance (ASCUS), low grade squamous intraepithelial lesion (LSIL) or cervical intraepithelial neoplasia grade 1 (CIN1) are acceptable. Individuals with a history of atypical glandular cells of uncertain significance (AGUS), HSIL or CIN2 and who have received subsequent evaluation and/or treatment with follow up normal PAP smear are eligible. Patient report will be accepted History of undiagnosed vaginal bleeding Use of a systemic, vaginal, or perineal antibiotic within 7 days prior to enrollment in this study Use of an immunosuppressive or immunomodulatory drug* for two or more consecutive weeks within 6 months prior to enrollment such as >0.5 mg/kg/day or >/=20 mg total dose/day of prednisone orally or >800 µg of inhaled beclomethasone (nasal and non-genital topical steroids are allowed) History of allergic reactions attributed to compounds of similar chemical or biologic composition to Monolaurin Vaginal Gel Uncontrolled concurrent illness*. Subjects with a history of organ or marrow transplant are excluded. Including, but not limited to, ongoing or active infection, active liver, kidney or autoimmune diseases (a history of thyroid disease will be permitted as long as the thyroid disease is now stable), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Acute illness within 3 days before receipt of study product (per investigator's discretion) Pregnant women and women who are planning to become pregnant within 30 days after the final study dose, or women who are breastfeeding Immunosuppression as a result of an underlying illness or treatment or use of anticancer chemotherapy or radiation therapy (cytotoxic) within the preceding 36 months Active neoplastic disease* or a history of any hematologic malignancy. Active neoplastic disease is defined as neoplastic disease or treatment for neoplastic disease within the past 5 years (excluding non-melanoma skin cancer) -Received an experimental agent* within 30 days before receipt of study product or expect to receive an experimental agent during the 1 month study period. (vaccine, drug, biologic, device, blood product, or medication) Any condition that would place the subject at an unacceptable risk of injury, render her unable to meet the requirements of the protocol, or that may interfere with successful completion of the study A history of alcohol or drug abuse* during the previous 1 year that in the opinion of the site investigator would interfere with study procedures For example, daily excessive alcohol use or frequent binge drinking as determined by the investigator, or daily marijuana use

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5% Monolaurin Vaginal Gel<br>80 subjects will receive 5% Monolaurin Gel twice daily for three successive days for a total of 6 doses | Drug: 5% Monolaurin Vaginal Gel<br>* Monolaurin Vaginal Gel is a clear and colorless, non-sterile glycol-based gel for vaginal administration , and commonly referred to as glycerol monolaurate (GML). Each subject will receive intravaginal gel twice daily for three successive days for a total of 6 doses. There will be 3 clinic visits over 30 days.<br>|
| Placebo Comparator: Vehicle Placebo<br>40 subjects will receive placebo Gel twice daily for three successive days for a total of 6 doses | Other: Placebo<br>* The placebo gel is a clear to opaque, colorless to light gray, non-sterile glycol-based gel for vaginal administration. The placebo gel contains the same excipients as the Monolaurin vaginal gel. Each subject will receive intravaginal gel twice daily for three successive days for a total of 6 doses. There will be 3 clinic visits over 30 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Cure in Each Study Arm | A clinical cure was defined by normal Amsel criteria, including: normal physiological vaginal discharge, whiff test negative for any amine fishy odor, saline wet mount less than 20% for clue cells, and vaginal pH is <=4.5. All four criteria had to be normal with none of the clinical failure criteria met to be considered a clinical cure. A clinical failure was defined by at least one of the following: one or more abnormal Amsel criteria, early discontinuation of study therapy due to lack of treatment effect, use of any vaginosis therapy other than study product during the study, or in the investigator's opinion, required additional treatment for vaginosis. | Visit 2 (Day 8-15) | 
| Number of Participants Reporting Solicited Urogenital Adverse Events (AEs) Following the First Dose of the Study Product | Solicited event assessments were captured on a memory aid starting on Day 1, the first day of therapy and continuing for 5 days. The participant recorded the presence and intensity of vulvovaginal solicited events on the memory aid. Any symptom that was present at the time that the participant was screened was considered as baseline and not reported as a solicited urogenital AE. However, if the symptom deteriorated during the reporting period, it was considered an AE. If a symptom was reported that was not present at baseline, it too was considered an AE. Any symptoms still present on Day 5 were followed by participant memory aid notations until symptom resolution. Solicited events collected include vaginal odor, vaginal pain, vaginal tenderness, vaginal itching, vaginal dryness, vaginal discharge, and vaginal inflammation. Severity of solicited events symptoms were graded as mild, moderate, or severe according to the grading table in the protocol. | Days 1 through 5 | 
| Number of Participants Reporting Serious Adverse Events (SAEs) Considered Product-related | The number of participants in each treatment group with product-related SAEs was assessed. An AE was considered serious if, in the view of either the investigator or sponsor, it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, or a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalizations could be considered serious when, based upon appropriate medical judgment, they could jeopardize the participant and require medical or surgical intervention to prevent one of the outcomes listed. An AE was considered related if there was a reasonable possibility that the study product caused the AE, meaning that there is evidence to suggest a causal relationship between the study product and the AE. | Visit 1 (Day 1) through Visit 3 (Day 22-31) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Therapeutic Cure in Each Study Arm | Therapeutic cure was defined as both a clinical cure and a bacteriological cure. All four Amsel criteria had to be normal with none of the clinical failure criteria listed met to be considered a clinical cure, including normal physiological vaginal discharge, whiff test negative for any amine fishy odor, saline wet mount less than 20% for clue cells, and vaginal pH is <=4.5. A clinical failure was defined by at least one of the following: one or more abnormal Amsel criteria, early discontinuation of study therapy due to lack of treatment effect, use of any vaginosis therapy other than study product during the study, or in the investigator's opinion, required additional treatment for vaginosis. A vaginal swab for bacteriological assessment of BV by Nugent criteria was performed. The Nugent score can range from 0 to 10. Bacteriological cure of BV was defined as a normal Nugent score of 0-3. Participants who were clinical failures, or had a Nugent score >3 were therapeutic failures. | Visit 2 (Day 8-15) | 
| Number of Participants With Therapeutic Cure in Each Study Arm | Therapeutic cure was defined as both a clinical cure and a bacteriological cure. All four Amsel criteria had to be normal with none of the clinical failure criteria listed met to be considered a clinical cure, including normal physiological vaginal discharge, whiff test negative for any amine fishy odor, saline wet mount less than 20% for clue cells, and vaginal pH is <=4.5. A clinical failure was defined by at least one of the following: one or more abnormal Amsel criteria, early discontinuation of study therapy due to lack of treatment effect, use of any vaginosis therapy other than study product during the study, or in the investigator's opinion, required additional treatment for vaginosis. A vaginal swab for bacteriological assessment of BV by Nugent criteria was performed. The Nugent score can range from 0 to 10. Bacteriological cure of BV was defined as a normal Nugent score of 0-3. Participants who were clinical failures, or had a Nugent score >3 were therapeutic failures. | Visit 3 (Day 22-31) | 
| Number of Participants With Nugent Score of 3 or Less (Negative for BV) in Each Study Arm | A vaginal swab for bacteriological assessment of BV by Nugent criteria was performed. The Nugent score utilizes a 10-point scale for evaluation of vaginal flora. The Nugent score can range from 0 to 10. A score of 7 to 10 is consistent with BV while 4-6 is considered intermediate and 0-3 is negative for BV. Bacteriological cure of BV was defined as a normal Nugent score of 0-3. | Visit 2 (Day 8-15) | 
| Number of Participants With Nugent Score of 3 or Less (Negative for BV) in Each Study Arm | A vaginal swab for bacteriological assessment of BV by Nugent criteria was performed. The Nugent score utilizes a 10-point scale for evaluation of vaginal flora. The Nugent score can range from 0 to 10. A score of 7 to 10 is consistent with BV while 4-6 is considered intermediate and 0-3 is negative for BV. Bacteriological cure of BV was defined as a normal Nugent score of 0-3. | Visit 3 (Day 22-31) | 
| Number of Participants With Nugent Score of 4-6 (Intermediate BV) in Each Study Arm | A vaginal swab for bacteriological assessment of BV by Nugent criteria was performed. The Nugent score utilizes a 10-point scale for evaluation of vaginal flora. The Nugent score can range from 0 to 10. A score of 7 to 10 is consistent with BV while 4-6 is considered intermediate and 0-3 is negative for BV. Bacteriological cure of BV was defined as a normal Nugent score of 0-3. | Visit 2 (Day 8-15) | 
| Number of Participants With Nugent Score of 4-6 (Intermediate BV) in Each Study Arm | A vaginal swab for bacteriological assessment of BV by Nugent criteria was performed. The Nugent score utilizes a 10-point scale for evaluation of vaginal flora. The Nugent score can range from 0 to 10. A score of 7 to 10 is consistent with BV while 4-6 is considered intermediate and 0-3 is negative for BV. Bacteriological cure of BV was defined as a normal Nugent score of 0-3. | Visit 3 (Day 22-31) | 
| Number of Participants With Clinical Cure in Each Study Arm | A clinical cure was defined by normal Amsel criteria, including: normal physiological vaginal discharge, whiff test negative for any amine fishy odor, saline wet mount less than 20% for clue cells, and vaginal pH is <=4.5. All four criteria had to be normal with none of the clinical failure criteria met to be considered a clinical cure. A clinical failure was defined by at least one of the following: one or more abnormal Amsel criteria, early discontinuation of study therapy due to lack of treatment effect, use of any vaginosis therapy other than study product during the study, or in the investigator's opinion, requires additional treatment for vaginosis. Participants who did not have enough information to determine a clinical cure or clinical failure status were not evaluable for clinical cure. | Visit 3 (Day 22-31) | 
| Number of Participants Experiencing Non-laboratory Non-solicited AEs Following the First Dose of the Study Product | The number of participants who experienced non-laboratory, non-solicited AEs following the first dose of the study product through Visit 3 (Day 22-31) was assessed. Events involving laboratory parameters that were not collected as part of the protocol were counted as non-laboratory, non-solicited adverse events. | Visit 1 (Day 1) through Visit 3 (Day 22-31) | 
| Number of Participants Experiencing Laboratory AEs Following the First Dose of the Study Product | The number of participants experiencing laboratory AEs following the first dose of the study product was assessed at Visit 2 (Day 8-15). A laboratory abnormality was considered an adverse event if there was a worsening of the laboratory value at Visit 2 from the baseline value and it increased in laboratory toxicity grading from the baseline toxicity grading. Protocol-defined hematology parameters assessed were white blood cells, hemoglobin, platelets, and neutrophils. Protocol-defined clinical chemistry parameters assessed were creatinine, AST, ALT, total bilirubin, and glucose (random). | Visit 2 (Day 8-15) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bacterial Vaginosis, Monolaurin Vaginal Gel