Safety Study of Lactobacillus Administered Vaginally to Healthy Women

The purpose of this study is to demonstrate that the new formulation of L. crispatus CTV-05
(LACTIN-V) is safe and well tolerated in healthy pre-menopausal women when administered
vaginally via a pre-filled applicator at a dose of 5.0 x 10^8, 1.0 x 10^9 or 2.0 x 10^9
cfu/dose daily for 5 consecutive days as compared to a placebo control substance containing
maltodextrin and a preservation matrix. Safety will be assessed by:

- Incidence and severity of adverse events through assessing symptoms, physical
examination findings, and signs of irritation involving the external genitalia, cervix
or vagina, including disruption of the epithelium and blood vessels as seen on pelvic
examination and colposcopy.

- Laboratory parameters including urinalysis, a complete blood count (CBC) with
differential, and chemistry panels to assess systemic effects of the study product.

The study will also evaluate the tolerability and acceptability of LACTIN-V in a pre-filled
applicator by:

- The proportion of participants who discontinue study product use due to overt adverse
events

- The proportion of participants who adhere to the complete dosing schedule

- Self-administered questionnaires and focus group discussions about acceptability of the
study product

Inclusion Criteria:

- 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.

- Vaginal and cervical anatomy that in the opinion of the Investigator lends itself
easily to colposcopy.

- Capable of providing informed consent and reading English.

- Previous sexual experience including vaginal intercourse.

- Previous experience of 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 3
(Day 14).

- 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 35.

- Agree to not use tampons throughout the trial period, from the time of screening until
Day 35.

- 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), use of condoms or abstinence.

Exclusion Criteria:

- Urogenital infection at screening or within the 21 days prior to screening. This
includes urinary tract infection, bacterial vaginosis, Trichomonas vaginalis,
Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum or Herpes simplex.
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.

- Antibiotic or antifungal therapy within 30 days of enrollment visit (vaginal or
systemic).

- Investigational drug use within 30 days or 10 half-lives of the drug, whichever is
longer, of enrollment visit. Planned investigational drug 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.

- Abnormal results for the pap smear at the screening visit.

- Known allergy to any component of LACTIN-V, other significant drug allergy or to latex
(condoms).

- Unavailable for follow-up visits.

- Known drug or alcohol abuse.

- At enrollment, have any social or medical condition (e.g., neurological,
gastrointestinal, renal, hepatic, cardiovascular, pulmonary, metabolic, endocrine,
hematological, genitourinary or other major disorder), or psychiatric illness (e.g.,
depression, schizophrenia) 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.