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Bacterial VaginosisPhase 2NCT03930745

Suppression Of Bacterial Vaginosis (BV) [SUBVert]

A Phase 2 study testing TOL-463 in people with Bacterial Vaginosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 years, women only
Conditions the study is for
Bacterial Vaginosis
What is being tested?
TOL-463
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
81 participants
Where
4 sitesUnited States
Study dates
9 Sep 2019to 6 Dec 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Screening Visit(s) Inclusion Criteria:
  • 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.
  • Willing and able to provide written informed consent;
  • Age 18-55 years of age at the time of V0;
  • General good health based on medical history, targeted physical examination, and pelvic examination;
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  • 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.
  • Have a negative urine pregnancy test at V0, if of childbearing potential;
  • 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:
  • 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.
  • Consistent use of a barrier method, including diaphragms or condoms, for at least 13 days prior to screening.
  • Abstinence from vaginal sexual intercourse for at least 13 days prior to screening.
  • Exclusively same-sex relationship.
  • Monogamous relationship with vasectomized partner.
  • 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.
  • Willing and able to provide Enrollment written informed consent;
  • 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.
  • Must have a negative urine pregnancy test at V1, if of childbearing potential;
  • 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.
  • Must agree to abstain from receptive oral, anal, and vaginal sexual intercourse one hour prior to IP administration and for 24 hours after;
  • Willing to refrain from using tampons or menstrual cups for 24 hours after IP administration;
  • 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:
  • 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.
  • Consistent use of a barrier method, including diaphragms or condoms, for at least 21 days prior to using IP.
  • Abstinence from vaginal sexual intercourse for at least 21 days prior to using IP.
  • Exclusively same-sex relationship.
  • Monogamous relationship with vasectomized partner.

Who cannot join

  • Screening Visit(s) Exclusion Criteria:
  • 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.
  • Concurrent Vulvovaginal Candidiasis (VVC) infection with inability to be treated with oral fluconazole;
  • 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).
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  • Results of Nucleic Acid amplification Test (NAAT) testing will be reviewed prior to enrollment.
  • Active genital lesions, including ulcers or vesicles consistent with herpes or warts;
  • Planned ongoing immunosuppressive therapy or systemic antibiotic treatment during the course of the study;
  • History of hypersensitivity, allergy or other contraindication(s) to metronidazole or other CDC-recommended BV treatment used to treat subject;
  • History of hypersensitivity to any TOL-463 formulation components;
  • Current or untreated cervical intraepithelial neoplasia (CIN) or cervical carcinoma;
  • Currently pregnant or nursing;
  • Any other condition that, in the opinion of the investigator, would interfere with participation in the study;
  • 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.
  • 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.
  • Use of vaginal or systemic antibiotic or antifungal since V0, other than oral metronidazole, CDC-recommended BV treatment, or oral fluconazole, as per protocol;
  • Evidence or suspicion of infectious cause of cervicitis or active genital lesion on pelvic examination at Visit 1, Enrollment (V1);
  • Concurrent VVC infection at V1 with inability to treat with oral fluconazole;
  • Use of any investigational drug within 30 days prior to V1 or planned/anticipated use during study participation.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • University of Alabama at Birmingham School of Medicine - Infectious Disease

    Birmingham, Alabama, 35205

  • Cook County Health and Hospitals System - Ruth M Rothstein CORE Center

    Chicago, Illinois, 60612

  • University of California, San Diego - Antiviral Research Center

    La Jolla, California, 92121

  • Magee Women's Hospital of UPMC - Reproductive Infectious Disease Research

    Pittsburgh, Pennsylvania, 15219

Other trials in United States

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled Trial Of TOL-463 Insert for Suppression Of Bacterial Vaginosis (BV) [SUBVert]

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.

Read the detailed description

This is 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. Secondary objectives of the study are: 1) to evaluate the time to BV recurrence as defined by clinical criteria, 2) to evaluate the incidence of vaginal symptoms over study participation, 3) to evaluate acceptability of a twice-weekly application of TOL-463 vaginal insert in suppression of BV, and 4) to evaluate the safety of TOL-463 vaginal insert compared to placebo, including the incidence of secondary vulvovaginal candidiasis (VVC). The null hypothesis for the comparison is that there is no difference in cure rates between treatments, with a two-sided alternative.

Being tested
Placebo, TOL-463
Keywords
Bacterial vaginosis, Candida albicans, Double-Blind, Gardnerella vaginalis, Phase II, Placebo, Randomized, Suppression, TOL-463 insert
Medical subject headings
Vaginosis, Bacterial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboOther

    Placebo vaginal inserts.

  • TOL-463Drug

    TOL-463 is a non-azole vaginal anti-infective drug candidate designed as a dual-indication therapy for BV and VVC.

Study groups in NCT03930745
Study groupRoleWhat they receive
Arm 1ExperimentalTOL-463 insert administered vaginally twice a week for twelve weeks. N=125
Receives: Drug: TOL-463
Arm 2Placebo comparatorMatching placebo insert administered vaginally twice a week for twelve weeks. N=125
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of Participants With Recurrent Bacterial Vaginosis (RBV) by Visit 4, as Defined by Presence of at Least 3 Amsel Criteria

    Recurrent bacterial vaginosis (RBV) was defined as the presence of at least three out of the following four Amsel criteria: positive KOH whiff test, homogeneous discharge characteristic of BV, clue cells comprising at least 20% of vaginal squamous epithelial cells, and vaginal pH > 4.5. Participants who had post-baseline efficacy results but were lost to follow-up before study completion were considered "treatment failures" and counted toward the number of participants with recurrence of BV.

    Measured: Day 1 through Day 91

Secondary outcomes (6)

  1. Time to Bacterial Vaginosis (BV) Recurrence, as Defined by Presence of at Least 3 Amsel Criteria

    Recurrent bacterial vaginosis (RBV) was defined as the presence of at least three out of the following four Amsel criteria: positive KOH whiff test, homogeneous discharge characteristic of BV, clue cells comprising at least 20% of vaginal squamous epithelial cells, and vaginal pH > 4.5. Participants who had post-baseline efficacy results but were lost to follow-up before study completion were censored in secondary time-to-event analyses. Participants with off-study diagnosis of BV were excluded from secondary time-to-event analyses.

    The median time to BV recurrence was calculated as the first event time at which the Kaplan-Meier estimator drops to or below 0.5.

    Measured: Day 1 through Day 91

  2. Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Abnormal Vaginal Discharge

    The BV symptoms evaluated for efficacy at each clinic visit included abnormal vaginal discharge and vaginal odor. Both symptoms were assessed by a clinician as either consistent with BV, not consistent with BV, or absent. Only symptoms deemed consistent with BV were reported as BV symptoms.

    Measured: Assessed at Visit 1 (Day 1), Visit 2 (Window: Days 29-35), Visit 3 (Window: Days 57-63) and Visit 4 (Window: Days 85-91).

  3. Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Vaginal Odor

    The BV symptoms evaluated for efficacy at each clinic visit included abnormal vaginal discharge and vaginal odor. Both symptoms were assessed by a clinician as either consistent with BV, not consistent with BV, or absent. Only symptoms deemed consistent with BV were reported as BV symptoms.

    Measured: Assessed at Visit 1 (Day 1), Visit 2 (Window: Days 29-35), Visit 3 (Window: Days 57-63) and Visit 4 (Window: Days 85-91).

  4. Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses

    The satisfaction questionnaire contained five questions assessing participant satisfaction with the study treatment. For questions regarding ease of use, frequency of use, and overall satisfaction, participants could respond on a scale ranging from "Extremely dissatisfied" to "Extremely satisfied." Participants who responded with "Somewhat satisfied" through "Extremely satisfied" were considered "Satisfied" with those categories. For the question regarding convenience of use, participants could respond on a scale ranging from "Extremely inconvenient" to "Extremely convenient." Participants who responded with "Somewhat convenient" through "Extremely convenient" were considered "Satisfied" with study treatment convenience. For the question of whether the participant would use the study treatment again, participants who responded with "Yes" were considered "Satisfied" with the study treatment.

    Measured: Assessed at study completion (the visit at which the participant was diagnosed with BV, or Visit 4 for participants remaining BV suppressed). This may occur at Visit 2 (Window: Days 29-35), Visit 3 (Window: Days 57-63) or Visit 4 (Window: Days 85-91).

  5. Number of Participants With Adverse Events (AEs) Considered Product-related Following Initiation of Study Treatment

    Safety was monitored throughout the study, including via participant reporting. Study clinicians assessed whether or not reported adverse events (AEs) were related to study treatment.

    Measured: Day 1 through Day 91

  6. Number of Participants With Culture Confirmed Secondary VVC Following Initiation of Study Treatment

    Assessment of vulvovaginal candidiasis (VVC) was performed by pelvic examination at baseline and at each follow-up visit. If clinical diagnosis of VVC was determined at any visit, then a confirmatory Candida culture was performed.

    Measured: Day 1 through Day 91

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2019
  2. Study start9 Sep 2019
  3. Primary completion6 Dec 2021
  4. Study completion6 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
81 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03930745
Sponsor's protocol ID
18-0017
Status last verified
27 May 2020
First submitted
25 Apr 2019
Last updated
22 Feb 2023
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TOL-463 in people with Bacterial Vaginosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Participants With Recurrent Bacterial Vaginosis (RBV) by Visit 4, as Defined by Presence of at Least 3 Amsel Criteria (time frame: Day 1 through Day 91). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03930745.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2023.

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