Suppression Of Bacterial Vaginosis (BV) [SUBVert]

NCT03930745 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 18-0017
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Bacterial Vaginosis

Keywords

Bacterial vaginosis; Candida albicans; Double-Blind; Gardnerella vaginalis; Phase II; Placebo; Randomized; Suppression; TOL-463 insert

Outcome Measures

Primary Outcomes (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.

  Day 1 through Day 91

Secondary Outcomes (6)

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

  Day 1 through Day 91

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

  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).

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

  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).

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

  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).

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

  Day 1 through Day 91

Study Arms (2)

Arm 1

EXPERIMENTAL

TOL-463 insert administered vaginally twice a week for twelve weeks. N=125

Drug: TOL-463

Arm 2

PLACEBO COMPARATOR

Matching placebo insert administered vaginally twice a week for twelve weeks. N=125

Other: Placebo

Interventions

Placebo OTHER

Placebo vaginal inserts.

Arm 2

TOL-463 DRUG

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

Arm 1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: Female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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).
• \*\*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;
• Active menses or significant vaginal bleeding as determined by the study clinician at V1\*;

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (4)

University of Alabama at Birmingham School of Medicine - Infectious Disease

Birmingham, Alabama, 35205, United States

Location

University of California, San Diego - Antiviral Research Center

La Jolla, California, 92121, United States

Location

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

Chicago, Illinois, 60612, United States

Location

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

Pittsburgh, Pennsylvania, 15219, United States

Location

MeSH Terms

Conditions

Vaginosis, Bacterial

Interventions

TOL-463

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vaginitis; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Results Point of Contact

• Title: Jeanne Marrazzo, MD, MPH
• Organization: University of Alabama at Birmingham School of Medicine

jmarrazzo@uabmc.edu

205-975-5500

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2019
• First Posted: April 29, 2019
• Study Start: September 9, 2019
• Primary Completion: December 6, 2021
• Study Completion: December 6, 2021
• Last Updated: February 22, 2023
• Results First Posted: February 22, 2023

Record last verified: 2020-05-27

Locations

US (4)