Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Placebo-Controlled Study Of TOL-463 Insert for Suppression Of Bacterial Vaginosis (BV)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03930745
Recruitment Status : Recruiting
First Posted : April 29, 2019
Last Update Posted : September 13, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
This is a double-blind, placebo-controlled study screening approximately 600 adult females 18-50 years of age 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.

Condition or disease Intervention/treatment Phase
Bacterial Vaginosis Other: Placebo Drug: TOL-463 Phase 2

Detailed Description:
This is a Phase II randomized, double-blind, placebo-controlled study screening approximately 600 adult females 18-50 years of age 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 using oral metronidazole, 500 mg twice a day for 7 days. It will be conducted at 2 sites in the US and last for 12 months with patient participation duration of 12 weeks. 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 recurrent BV (RBV) following successful induction with oral metronidazole. 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; 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Trial Of TOL-463 Insert for Suppression Of Bacterial Vaginosis (BV)
Actual Study Start Date : September 9, 2019
Estimated Primary Completion Date : July 1, 2020
Estimated Study Completion Date : July 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaginal Diseases

Arm Intervention/treatment
Experimental: Arm 1
TOL-463 insert administered vaginally twice a week for twelve weeks. N=125
Drug: TOL-463
TOL-463 is a non-azole vaginal anti-infective drug candidate designed as a dual-indication therapy for BV and VVC.

Placebo Comparator: Arm 2
Matching placebo insert administered vaginally twice a week for twelve weeks. N=125
Other: Placebo
Placebo vaginal inserts.




Primary Outcome Measures :
  1. Proportion of participants with recurrent Bacterial Vaginosis (RBV) defined by presence of more than 2 Amsel criteria, by Visit 4 [ Time Frame: Day 85 through Day 91 ]

Secondary Outcome Measures :
  1. Number of participants satisfied with TOL-463 treatment assessed by satisfaction questionnaire responses [ Time Frame: Day 29 through Day 91 ]
  2. Occurrence of Adverse Events (AEs) [ Time Frame: Day 1 through Day 91 ]
  3. Occurrence of culture confirmed secondary Vulvovaginal Candidiasis (VVC) [ Time Frame: Day 1 through Day 91 ]
  4. Proportion of participants reporting Bacterial Vaginosis (BV) symptoms [ Time Frame: Day 29 through Day 91 ]
  5. Time to Bacterial Vaginosis (BV) recurrence [ Time Frame: Day 29 through Day 91 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 KOH whiff test; vaginal pH of > 4.5; and > / = 20% clue cells.

  2. Willing and able to provide written informed consent;
  3. Age 18-50 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, The Papanicolaou test (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;
  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 for at least 1 year, status post bilateral oophorectomy or 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, 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;
  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 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 for at least 1 year, status post bilateral oophorectomy or 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**positive;

    ** Women may be rescreened for eligibility following successful treatment of confounding STI.

    Positive results of 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 use or unwilling to be treated with oral metronidazole;
  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;

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 or oral fluconazole, as per protocol;
  3. Evidence or suspicion of infectious cause of cervicitis or active genital lesion on pelvic examination at 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03930745


Contacts
Layout table for location contacts
Contact: Jeanne M. Marrazzo 12059755500 jmarrazzo@uabmc.edu

Locations
Layout table for location information
United States, Alabama
University of Alabama at Birmingham School of Medicine- Infectious Disease Recruiting
Birmingham, Alabama, United States, 35205
United States, Pennsylvania
Magee Women's Hospital of UPMC - Reproductive Infectious Disease Research Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15219
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03930745     History of Changes
Other Study ID Numbers: 18-0017
HHSN272201300012I
First Posted: April 29, 2019    Key Record Dates
Last Update Posted: September 13, 2019
Last Verified: April 24, 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Bacterial vaginosis
Candida albicans
Double-Blind
Gardnerella vaginalis
Phase II
Placebo
Randomized
Suppression
TOL-463 insert
Additional relevant MeSH terms:
Layout table for MeSH terms
Vaginosis, Bacterial
Vaginal Diseases
Genital Diseases, Female
Bacterial Infections
Vaginitis