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