Suppression Of Bacterial Vaginosis (BV) [SUBVert]
Condition: Bacterial Vaginosis
MeSH terms: Vaginosis, Bacterial; Vaginal Diseases
Intervention: Placebo; TOL-463
Intervention description: Placebo vaginal inserts.; TOL-463 is a non-azole vaginal anti-infective drug candidate designed as a dual-indication therapy for BV and VVC.
Intervention MeSH terms: TOL-463
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 81.0
Sex: Female
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Bacterial vaginosis; Candida albicans; Double-Blind; Gardnerella vaginalis; Phase II; Placebo; Randomized; Suppression; TOL-463 insert

Summary:

      A Phase II randomized, double-blind, placebo-controlled study screening approximately 600
      adult females, aged 18-55, with a goal to enroll approximately 250 participants to achieve
      200 evaluable participants at the test of cure (TOC) visit. The study is designed to
      determine the clinical efficacy of an investigational product (IP), TOL-463 Insert, in
      suppressing Recurrent Bacterial Vaginosis (RBV) when administered to women who have a history
      of RBV and have been successfully cleared of their current Bacterial Vaginosis (BV) infection
      administering 500 mg of oral metronidazole, twice a day for 7 days or another CDC-recommended
      BV treatment. Patient participation will be approximately 100 days while the study is
      conducted at 4 sites within the United States. The primary objective of the study is to
      evaluate the clinical efficacy of a twice-weekly application of TOL-463 vaginal insert in
      suppression of BV in women with a history of RBV following successful induction with oral
      metronidazole or a CDC-recommended BV treatment.
    

Eligibility criteria:

        Inclusion Criteria:

        Screening Visit(s) Inclusion Criteria:

          1. Women with a current Bacterial Vaginosis (BV) infection and a history of at least two
             previous episodes of BV by documentation or self-report in the past year. Screening
             (V0) diagnosis is based on the presence of > / = 3 Amsel criteria*;

               -  Homogeneous vaginal discharge; positive potassium hydroxide (KOH) whiff test;
                  vaginal pH of > 4.5; and > / = 20% clue cells.

          2. Willing and able to provide written informed consent;

          3. Age 18-55 years of age at the time of V0;

          4. General good health based on medical history, targeted physical examination, and
             pelvic examination;

          5. For participants 21 years of age or older, Pap test performed within the past 3 years,
             with the most recent result being normal or Atypical Squamous Cells of Undetermined
             Significance (ASCUS) Human Papillomavirus (HPV) negative or Pap smear collected at
             V0*;

             *Consistent with current Pap screening guidelines, a Pap smear must be performed at
             V0, for women who meet the following criteria and cannot provide documentation or
             self-report of a normal or ASCUS HPV negative Pap smear, conducted within the prior 3
             years: (a) has not had a hysterectomy or (b) has had a hysterectomy and has a history
             of cervical intraepithelial neoplasia grade 2 plus (CIN2plus) in the past 20 years.

             Note: If a Pap smear is conducted at V0, the results are not required prior to
             enrollment.

          6. Have a negative urine pregnancy test at V0, if of childbearing potential;

          7. Must be of non-childbearing potential* or must be using an effective method of birth
             control** and must be willing to continue the method through the end of
             Investigational Product (IP) administration;

             *Defined as post-menopausal or status post bilateral tubal ligation, or status post
             bilateral oophorectomy or status post hysterectomy.

             **Acceptable methods are defined as:

               1. Intrauterine Devices (IUDs) or hormonal contraceptives for at least 22 days prior
                  to screening. Note: Intravaginal contraceptive rings (e.g., NuvaRing) are not
                  acceptable forms of birth control for this study.

               2. Consistent use of a barrier method, including diaphragms or condoms, for at least
                  13 days prior to screening.

               3. Abstinence from vaginal sexual intercourse for at least 13 days prior to
                  screening.

               4. Exclusively same-sex relationship.

               5. Monogamous relationship with vasectomized partner.

          8. Willing and able to cooperate to the extent and degree required by this protocol at
             the discretion of the investigator;

        Enrollment Visit Inclusion Criteria:

        In addition to confirming all relevant Screening Visit Inclusion Criteria, women must meet
        all of the following criteria to be eligible for enrollment in the study.

          1. Willing and able to provide Enrollment written informed consent;

          2. After completion of metronidazole induction therapy or another CDC-recommended BV
             treatment, no clinical evidence of BV* and absence of symptoms of BV** at Visit 1,
             Enrollment (V1);

               -  As defined by < / = 2 of 4 Amsel criteria. **Defined as absence of vaginal
                  discharge and odor consistent with BV.

          3. Must have a negative urine pregnancy test at V1, if of childbearing potential;

          4. Willing to refrain from any intravaginal products/medications* other than the IP
             throughout the course of the trial;

             *For example: douches, antifungal or antibacterial preparations, lubricants,
             contraceptive creams, gels, foams, sponges, spermicides.

          5. Must agree to abstain from receptive oral, anal, and vaginal sexual intercourse one
             hour prior to IP administration and for 24 hours after;

          6. Willing to refrain from using tampons or menstrual cups for 24 hours after IP
             administration;

          7. Must be of non-childbearing potential* OR must be using an effective method of birth
             control** and must be willing to continue the method through the end of IP
             administration; *Defined as post-menopausal or status post bilateral tubal ligation,
             or status post bilateral oophorectomy or status post hysterectomy.

               -  Acceptable methods are defined as:

                    1. IUDs or hormonal contraceptives for at least 30 days prior to using IP.
                       Note: Intravaginal contraceptive rings (e.g., NuvaRing) are not acceptable
                       forms of birth control for this study.

                    2. Consistent use of a barrier method, including diaphragms or condoms, for at
                       least 21 days prior to using IP.

                    3. Abstinence from vaginal sexual intercourse for at least 21 days prior to
                       using IP.

                    4. Exclusively same-sex relationship.

                    5. Monogamous relationship with vasectomized partner.

        Exclusion Criteria:

        Screening Visit(s) Exclusion Criteria:

          1. Diagnosis of another vaginal or vulvar condition that may confuse interpretation of
             response to Investigational product (IP)*;

               -  For example: erosive lichen planus, desquamative inflammatory vaginitis, or
                  contact dermatitis involving the vulvar epithelium.

          2. Concurrent Vulvovaginal Candidiasis (VVC) infection with inability to be treated with
             oral fluconazole;

          3. Infectious cause of cervicitis (e.g., N. gonorrhoeae, C. trachomatis, or T. vaginalis)
             confirmed on physical examination and/or with laboratory testing*, **;

             *Women may be rescreened for eligibility following successful treatment of confounding
             Sexually Transmitted Infection (STI).

             **Results of Nucleic Acid amplification Test (NAAT) testing will be reviewed prior to
             enrollment.

          4. Active genital lesions, including ulcers or vesicles consistent with herpes or warts;

          5. Planned ongoing immunosuppressive therapy or systemic antibiotic treatment during the
             course of the study;

          6. History of hypersensitivity, allergy or other contraindication(s) to metronidazole or
             other CDC-recommended BV treatment used to treat subject;

          7. History of hypersensitivity to any TOL-463 formulation components;

          8. Current or untreated cervical intraepithelial neoplasia (CIN) or cervical carcinoma;

          9. Currently pregnant or nursing;

         10. Any other condition that, in the opinion of the investigator, would interfere with
             participation in the study;

         11. Previous enrollment in the study or at the investigator's discretion;

        Enrollment Visit Exclusion Criteria:

        In addition to confirming all Screening Visit Exclusion Criteria, women who meet any of the
        following criteria will not be eligible for enrollment in the study.

          1. Active menses or significant vaginal bleeding as determined by the study clinician at
             V1*;

             *Note: women who are menstruating may be reevaluated for study enrollment within the
             enrollment window.

          2. Use of vaginal or systemic antibiotic or antifungal since V0, other than oral
             metronidazole, CDC-recommended BV treatment, or oral fluconazole, as per protocol;

          3. Evidence or suspicion of infectious cause of cervicitis or active genital lesion on
             pelvic examination at Visit 1, Enrollment (V1);

          4. Concurrent VVC infection at V1 with inability to treat with oral fluconazole;

          5. Use of any investigational drug within 30 days prior to V1 or planned/anticipated use
             during study participation.