Safety and Efficacy Study of Lactobacillus Administered Vaginally in Women With Bacterial Vaginosis

Study Overview
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Brief Summary
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This is a phase IIa clinical trial in women with bacterial vaginosis. This study will determine whether treatment with vaginal lactobacillus in combination with antibiotic therapy (metronidazole) is effective in colonizing the vagina with the lactobacillus bacteria found in normal vaginal flora.

Detailed Description
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Phase IIa randomized, double blind, placebo-controlled, clinical trial of LACTIN-V at 2 x 10^9 cfu/dose versus placebo, administered vaginally with a pre-filled applicator once daily for five consecutive days followed by a weekly dose over 2 additional weeks after an initial standardized antibiotic treatment with 0.75% topical metronidazole (MetroGel). A single site will enroll 40 participants (30 randomized to LACTIN-V and 10 to placebo). Colonization rate of Lactobacillus crispatus CTV 05 will be assessed with culture and rep-PCR. Safety will be determined by comparing the incidence of adverse events and serious adverse events in the LACTIN-V and placebo groups as determined by clinical symptoms, physical examination, pelvic examination with colposcopy and laboratory measurements. Tolerability will be measured by percentage of subjects who discontinue study product use due to overt adverse events and percentage of subjects who adhere to complete dosing schedule. Acceptability will be assessed via a standardized questionnaire and focus group discussions.

Official Title
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A Phase IIa Study of the Colonization Efficiency, Safety and Acceptability of LACTIN-V Administered Vaginally to Women With Bacterial Vaginosis

Conditions
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Bacterial Vaginosis

Intervention / Treatment
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* Drug: LACTIN-V
* Drug: Placebo control substance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Untreated BV (asymptomatic or symptomatic) as diagnosed during the screening visit using Amsel criteria AND confirmed in the laboratory using the Nugent scoring system (Nugent Score ≥ 7). Otherwise healthy pre-menopausal women 18-40 years of age at date of screening. Regular menstrual cycles (21-35 days) or amenorrheic for at least 3 months due to use of a long acting progestin or continuous use of oral contraceptives. Subject is willing to insert pre-filled vaginal applicators. Subject is willing to be asked questions about personal medical health and sexual history. Normal Pap smear collected at the screening visit. If a subject's Visit 0 Pap smear result is any of the following, the person is ineligible for participation: ASC-US (atypical squamous cells of undetermined significance), AGC (atypical glandular cells), ASC-H (atypical squamous cells, cannot r/o high grade lesion), LSIL (low grade squamous intraepithelial lesions), HSIL (high grade squamous intraepithelial lesions), adenocarcinoma in situ, adenocarcinoma, squamous cell carcinoma in situ, squamous cell carcinoma or inadequate sample. Vaginal and cervical anatomy that in the opinion of the Investigator lends itself easily to colposcopy. Capable of reading and writing English and providing informed consent. Previous sexual experience including vaginal intercourse. Previous gynecological examinations. Currently in a mutually monogamous sexual relationship or not sexually active. Agree to be sexually abstinent 72 hours prior to Visit 1 (enrollment) until Visit 2 (Day 10). Also, agree to refrain from intercourse for 48 hours after the study product application on Day 12 and 19 as well as 72 hours before the last study visit on Day 28. Agree to abstain from the use of any other intravaginal product (i.e., contraceptive creams, gels, foams, sponges, lubricants, douches, etc.) throughout the trial period, from the time of screening until Day 28. Agree to abstain from using tampons throughout the trial period, from the time of screening until Day 28. Agree to use an adequate method of birth control for the duration of the study to avoid pregnancy. Acceptable methods include a history of tubal ligation, male partner with a vasectomy, a steroidal contraceptive (oral, patch, injectable or implantable), IUD (Paragard or Mirena), condoms or abstinence. Subject must have access to functioning refrigerator. Exclusion Criteria: Urogenital infection at screening or within the 21 days prior to screening. This includes urinary tract infection, Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis or Treponema pallidum. Subjects may be re-screened at least 21 days after the respective antibiotic or antifungal therapies have been completed. History of recurrent genital herpes. Diagnosis of N. gonorrhoeae, C. trachomatis, T. pallidum or T. vaginalis on two or more occasions during the six months prior to screening. Pregnancy or within 2 months of last pregnancy (all subjects will have a urine pregnancy test prior to enrollment). Lactation. Vaginal or systemic antibiotic or antifungal therapy within 21 days of the Screening visit or within 30 days of Enrollment visit. Investigational drug use within 30 days or 10 half-lives of the drug, whichever is longer, of enrollment visit. Planned investigational drug use while participating in this study. Menopause. IUD insertion or removal within the last 3 months. Pelvic surgery within the last 3 months. Cervical cryotherapy or cervical laser within the last 3 months. Use of a NuvaRing® within 3 days of the screening visit or during the course of the study. New long-acting treatments (e.g. depot formulation including medroxyprogesterone acetate (DMPA) form of hormonal birth control). Subjects may be enrolled if stable (> 3months) on existing therapy as determined by the Principal Investigator. Diabetes or other significant disease or acute illness that in the Investigator's assessment could complicate the evaluation. Known HIV infection or positive HIV test at screening. Immunosuppressive drug within 60 days. Previous participation in a L. crispatus CTV-05 clinical study. Colposcopic findings at the enrollment visit involving significant deep disruption of the epithelium. Known allergy to any component of LACTIN-V, other significant drug allergy or to latex (condoms). Unavailable for follow-up visits. History of drug or alcohol abuse. At enrollment, have any social or medical condition, or psychiatric illness that, in the opinion of the Investigator, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Vaginal application of single-use applicators pre-filled with LACTIN-V (Formulation 1) at 2 x 10^9 cfu/dose. The study product will be administered once daily for 5 consecutive days, followed by once weekly application over 2 consecutive additional weeks. | Drug: LACTIN-V<br>* Vaginal application of single-use applicators pre-filled with LACTIN-V (Formulation 1) at 2 x 10^9 cfu/dose or placebo control substance. The study product will be administered once daily for 5 consecutive days, followed by once weekly application over 2 consecutive additional weeks.<br>|
| Placebo Comparator: 2<br>Vaginal application of single-use applicators pre-filled with placebo control substance. The study product will be administered once daily for 5 consecutive days, followed by once weekly application over 2 consecutive additional weeks. | Drug: Placebo control substance<br>* Vaginal application of single-use applicators pre-filled with placebo control substance. The study product will be administered once daily for 5 consecutive days, followed by once weekly application over 2 consecutive additional weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the vaginal colonization efficiency of L. crispatus CTV-05 after vaginal administration of LACTIN-V at 2 x 10^9 cfu/dose (600 mg) daily for 5 days followed by weekly applications over 2 additional weeks |  | 4 weeks after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety of L. crispatus, LACTIN-V in otherwise healthy pre-menopausal women with BV, immediately after standardized antibiotic treatment with 0.75% topical metronidazole |  | 10 days and 4 weeks after intervention | 
| To evaluate the tolerability and acceptability of LACTIN-V as a powder in a pre-filled applicator |  | 4 weeks after intervention | 
| To evaluate and compare vaginal flora by Gram stain before and after receipt of LACTIN-V or placebo. |  | 10 days and 4 weeks after intervention | 
| To identify and compare bacteria colonizing the vagina at screening in women with bacterial vaginosis and after antibiotic and probiotic treatment. |  | Before intervention and 4 weeks after intervention | 
| To measure and compare the 4 week cure rate of BV after receipt of MetroGel in women who receive LACTIN-V or placebo. |  | 4 weeks after intervention | 
| To measure the rate of vaginal colonization by Candida sp. and symptomatic vaginal candidiasis after receiving LACTIN-V or placebo |  | 4 weeks after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bacterial Vaginosis, BV, UCSF, SFGH