LACTIN-V Study for Recurrent Bacterial Vaginosis

This is a Phase II-b multicenter randomized double-blind placebo-controlled trial to assess
the efficacy of repeated doses of LACTIN-V compared to placebo in preventing BV recurrence in
women diagnosed with BV. The study will also assess the safety of LACTIN-V by comparing the
incidence of AEs between women randomized to LACTIN-V or placebo. The study plans to enroll
228 non-pregnant, pre-menopausal women age 18 to 45 years. Women will be randomized 2:1 to
receive LACTIN-V or placebo. Potentially eligible women will start a standard 5-day course of
MetroGel. Women will return to the study clinic within 2 days after completing the 5-day
course of MetroGel to re-evaluate eligibility criteria and review the BV test results from
the screening visit. Women with Amsel criteria > /=3 and Nugent score 4-10 will be instructed
to administer the LACTIN-V or placebo at home for 5 consecutive days and then twice weekly
for 10 weeks. The primary objectives of this study are: 1) To estimate the efficacy of
repeated doses of LACTIN-V (2 x109 cfu/dose) as compared to placebo in preventing BV
recurrence by 12 weeks following treatment of BV with MetroGel vaginal gel (MetroGel). 2) To
assess the safety of LACTIN-V over 24 weeks by comparing the incidence of AEs between
individuals randomized to LACTIN-V or placebo. Secondary objectives are: 1) To investigate
the colonization of LACTIN-V (presence of L. crispatus CTV-05 in the vaginal specimen) and
fluctuations over 12 weeks, in relation to menses and sexual intercourse 2) To evaluate user
acceptability and tolerability of LACTIN-V over 12 weeks, including perceptions around method
of delivery and dosing. 3) To measure long-term colonization of LACTIN-V at 24 weeks (12
weeks after last dosing) 4) To estimate the long-term efficacy of repeated doses of LACTIN-V
(2 x 109 cfu/dose) as compared to placebo in preventing BV recurrence at 24 weeks (12 weeks
after last dosing)

Inclusion Criteria:

1. Capable of reading and writing English and voluntarily provide written informed consent
to participate in the study and comply with all study procedures 2. Untreated BV
(asymptomatic or symptomatic) as diagnosed during the screening visit defined by >/=3 Amsel
criteria. Note: Amsel criteria include the following: --Homogeneous, thin, grayish-white
discharge that smoothly coats the vaginal walls; --Vaginal pH >4.5; --Positive whiff-amine
test, defined as the presence of a fishy odor when a drop of 10% potassium hydroxide (KOH)
is added to a sample of vaginal discharge; --Presence of clue cells (>20% on microscopy).
3. Untreated BV(asymptomatic or symptomatic) as confirmed in the laboratory using the
Nugent scoring system (Nugent Score >/= 4) 4. Otherwise healthy pre-menopausal women 18-45
years of age on the day of screening 5. Regular predictable menstrual cycles or amenorrheic
for at least 3 months due to use of a long-acting progestin or continuous use of oral
contraceptives 6. Willing to be asked questions about personal medical health and sexual
history. 7. Willing to apply study agent vaginally and comply with study examinations. 8.
Agree to abstain from sexual intercourse during the first 5 consecutive days of study
product administration, 12 hours prior to study visits and for 12 hours after each study
product application 9. Agree to abstain from the use of any other intravaginal product
throughout the trial period from the time of screening through Visit 7 (Week 24, Day 168)
Note: Intravaginal products include contraceptive creams such as Gynol II, gels, foams,
sponges, lubricants not approved by the study investigators, and douches. Limit use of
tampons during menstruation to unscented products. 10. Must be of non-childbearing
potential or if of childbearing potential, must agree to use a reliable method of birth
control for the duration of the study Note: Reliable methods of birth control include tubal
ligation, male partner with a vasectomy, a steroidal contraceptive (oral, patch, injectable
or implantable), IUD, condoms or abstinence.

Exclusion Criteria:

1. Urogenital infection at screening Note: Urogenital infection includes urinary tract
infection, Trichomonas (T.) vaginalis, Neisseria (N.) gonorrhoeae, Chlamydia (C.)
trachomatis, Treponema (T.) pallidum, or vulvo-vaginal candidiasis. 2. Diagnosis of two or
more outbreaks of N. gonorrhoeae, C. trachomatis, T. pallidum, T. vaginalis, or herpes
simplex virus (herpes genitalis) within 6 months prior to screening 3. Positive for
syphilis or HIV at screening 4. Current pregnancy or within 2 months of last pregnancy
and/or currently breastfeeding**. Criteria will be assessed at screening and enrollment. 5.
Vaginal or systemic antibiotic or antifungal therapy (other than MetroGel given as part of
study procedures) within 21 days of screening or within 30 days of enrollment** 6. Use of
disulfiram within past 2 weeks or other contraindication to use of MetroGel** 7. Any
condition requiring regular periodic use of systemic antibiotics during participation in
the trial 8. Active genital herpes lesion** (if not resolved by enrollment)** 9.
Investigational drug use other than LACTIN-V within 30 days or 10 half-lives of the drug,
whichever is longer, of enrollment visit** 10. Other planned participation in an
investigational drug study while participating in this study** 11. Menopause defined as
more than 12 consecutive months of amenorrhea without another known cause including
pregnancy 12. IUD insertion or removal, pelvic surgery, cervical cryotherapy or cervical
laser treatment within the last 2 months prior to screening 13. Use of vaginal ring (eg,
NuvaRing) within 3 days of screening or during the course of the study** 14. Failure to
complete 5 days of MetroGel with the last dose taken no later than 48 hours prior to
randomization*** 15. Use of new long-acting hormonal treatments. Participant may be
enrolled if stable (>3 months) on existing therapy as determined by the principal
investigator** 16. Known allergy to any component of LACTIN-V/placebo or MetroGel or to
nitroimidazole derivatives or latex (condoms) 17. Any social, medical, or psychiatric
condition, including history of drug or alcohol abuse that in the opinion of the
investigator would make it unlikely for the participant to comply with the study ** Note:
Criteria will be assessed at screening and enrollment. ***Note: Criteria will be assessed
at enrollment