Vaginal lIve Biotherapeutic RANdomized Trial

NCT06135974 | Completed Early Phase 1 FDA Drug

• 1 other identifier: VMRC001
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 2

Brief Summary

The goal of this randomized clinical trial is to evaluate safety and biologic effect of a multi-strain vaginal L. crispatus live biotherapeutic product (LBP) in people receiving antibiotic treatment for bacterial vaginosis (BV). The main question\[s\] it aims to answer are whether the intervention is safe, and whether the strains of L. crispatus will colonize recipients' vagina. The study will evaluate one LBP with 6 strains of L. crispatus (LC106) and one LBP with 15 strains (LC115) vs. placebo. Participants will:

• be treated with oral antibiotics for BV
• receive 7 days of vaginal study product
• collect daily home swabs and make short daily diary entries for 5 weeks, including the week of antibiotic treatment and the week of study product treatment. Researchers will compare the 3 groups receiving different dosing strategies of LC106 and 1 group receiving LC115 vs. 1 group receiving placebo to see if the live biotherapeutic strains colonize the vagina after antibiotic treatment for BV.

Conditions

Bacterial Vaginosis

Keywords

live biotherapeutic; bacterial vaginosis; vaginitis

Outcome Measures

Primary Outcomes (2)

• Detection of LBP strains by metagenomic sequencing

  Detection of any one strain from the LBP at 5% relative abundance or greater, or any combination of strains at 10% relative abundance or greater using shotgun metagenomic sequencing

  Over 5 weeks

• Adverse events

  Assessment of safety by comparing number and severity of adverse events

  Over 12 weeks

Secondary Outcomes (5)

• Kinetics of colonization

  Over 12 weeks

• Recurrent BV by Amsel and Nugent criteria

  Over 12 weeks

• Non-iners Lactobacillus dominance and abundance

  Over 12 weeks

• Alpha and beta diversity of the microbial community

  Over 12 weeks

• Proportion of participants reporting product was acceptable to use

  Over 12 weeks

Other Outcomes (1)

• Comparison of detection of LBP strains by metagenomics between US and South Africa

  Over 12 weeks

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Vaginal placebo tablet administered daily for 7 days starting after antibiotic treatment

Drug: Placebo; Drug: Metronidazole Oral

LC106 7 days

EXPERIMENTAL

Vaginal live biotherapeutic product with 6 strains of L. crispatus, administered daily for 7 days after antibiotic treatment

Drug: LC106; Drug: Metronidazole Oral

LC106 3 days

EXPERIMENTAL

Vaginal live biotherapeutic product with 6 strains of L. crispatus, administered daily for 3 days after antibiotic treatment and packaged with 4 tablets of placebo to maintain masking (so a total of 7 tablets)

Drug: LC106; Drug: Metronidazole Oral

LC106 7 days, early start

EXPERIMENTAL

Vaginal live biotherapeutic product with 6 strains of L. crispatus, administered daily for 7 days starting on the 3rd day of antibiotic treatment

Drug: LC106; Drug: Metronidazole Oral

LC115

EXPERIMENTAL

Vaginal live biotherapeutic product with 15 strains of L. crispatus, administered daily for 7 days after antibiotic treatment

Drug: LC115; Drug: Metronidazole Oral

Interventions

LC106 DRUG

Tablet containing at least 2 x 10\^6 CFU/tablet, and comprised of 6 strains of Lactobacillus crispatus

LC106 3 days; LC106 7 days; LC106 7 days, early start

LC115 DRUG

Tablet containing at least 2 x 10\^6 CFU/tablet, and comprised of 15 strains of Lactobacillus crispatus

LC115

Placebo DRUG

Vaginal tablets containing primarily microcrystalline cellulose and no live bacteria

Placebo

Metronidazole Oral DRUG

Metronidazole tablet orally twice daily for 7 days

LC106 3 days; LC106 7 days; LC106 7 days, early start; LC115; Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Premenopausal individuals, 18- 40 years old
• BV by Amsel criteria (at least 3 of 4 criteria must be present)
• Abnormal Nugent score: ≥ 7
• Willing and able to provide written informed consent.
• HIV uninfected (by HIV Ab/Ag test at enrollment)
• Not pregnant by pregnancy test at enrollment, and unlikely to have an early pregnancy per clinician's assessment of last menstrual period and recent sexual activity.
• On continuous oral contraceptives (US site) or injectable progestin contraceptives (South African site) that suppress menstrual cycles, or willing to suppress menstrual cycles with one of these types of hormonal contraceptives
• Willing and able to attend study visits and comply with study procedures

You may not qualify if:

• History of clinically significant vaginal, cervical, or uterine disease including but not limited to: cancer of the female reproductive tract
• Prior hysterectomy
• Use of antibiotics in the past 30 days
• Syphilis (positive screen at enrollment)
• Vulvovaginal candidiasis (positive microscopy at enrollment)
• Allergy to or contraindication to use of oral metronidazole
• Currently participating in another study of an investigational product (excluding COVID vaccine studies)
• Use of long-acting systemic investigational product (e.g. injectable PrEP) within the past year
• Subject taking any of the following medications currently or in the past 30 days: systemic steroids (inhaled or nasal steroid therapy is permitted), interleukins, systemic interferons (e.g. local injection of interferon alpha for treatment of human papillomavirus is permitted) or systemic chemotherapy.
• History of coronary artery disease, myocardial infarction, chronic obstructive pulmonary disease, chronic renal failure, decompensated cirrhosis, or any other condition that in the opinion of the investigator will compromise ability to participate in the study.
• Use of an IUD (intrauterine device)
• Use of probiotics, prebiotics or synbiotics (supplements and products, oral or vaginal) within past 30 days. (NOTE: Oral yogurt with live cultures is allowed, as are fermented foods.)
• Active COVID-19 infection (determined by a positive PCR test of a nasal or nasopharyngeal swab) or recent exposure (\< 14 days) to someone with confirmed COVID-19 infection (an exposure is considered being within 6 feet/180 cm of someone without a mask for more than 15 minutes). Potential participants who meet these criteria can delay screening until they have completed isolation or quarantine.
• Vaginal cleansing practices in the past 30 days (i.e. vaginal products for cleaning or drying, vaginal douching) (by eligibility questionnaire)
• Any other condition or situation that in the opinion of the investigator will compromise ability to participate in the study.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Bill and Melinda Gates Foundation: collaborator
• Ragon Institute of MGH, MIT and Harvard: collaborator
• Centre for the AIDS Programme of Research in South Africa: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

CAPRISA - Vulindlela

Msunduzi Municipality, KwaZulu-Natal, South Africa

Location

Related Publications (2)

• Milford C, Dlamini BL, Mafunda NA, Hardwick TS, Lewis L, Khan AA, Mdladla MN, Mitchell CM, Potloane D. Bacterial Vaginosis [BV] knowledge, attitudes and behavioural changes after BV diagnosis among women enrolled in a clinical trial in Boston, USA and Vulindlela, South Africa: a qualitative study. BMC Womens Health. 2025 Dec 12. doi: 10.1186/s12905-025-04210-3. Online ahead of print.

  PMID: 41382078 DERIVED

• Chetty C, Mafunda N, Happel AU, Khan A, Cooley Demidkina B, Yende-Zuma N, Saidi Y, Mahabeer Polliah A, Lewis L, Osman F, Radebe P, Passmore JS, Kwon D, Ravel J, Ngcapu S, Liebenberg L, Symul L, Holmes S, Mitchell CM, Potloane D. Randomized trial of multi-strain Lactobacillus crispatus vaginal live biotherapeutic products after antibiotic therapy for bacterial vaginosis: study protocol for VIBRANT (vaginal lIve biotherapeutic RANdomized trial). Contemp Clin Trials Commun. 2025 Sep 16;48:101554. doi: 10.1016/j.conctc.2025.101554. eCollection 2025 Dec.

  PMID: 41050878 DERIVED

MeSH Terms

Conditions

Vaginosis, Bacterial; Vaginitis

Interventions

Metronidazole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Caroline Mitchell, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study product is labeled in a blinded manner with a code. Only pharmacy will have the link to the code and treatment assignment. However, the one arm starting study product during antibiotic treatment will be unblinded for both participants and investigators. However, the laboratory staff conducting the analyses for the primary and secondary outcomes will remain masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Obstetrics, Gynecology & Reproductive Biology

Model Details: This is a randomized trial with 5 arms

Study Record Dates

• First Submitted: November 2, 2023
• First Posted: November 18, 2023
• Study Start: February 1, 2024
• Primary Completion: December 26, 2024
• Study Completion: February 18, 2025
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Once primary and secondary analyses are completed.
• Access Criteria: Requesters must have appropriate human subjects approval or waiver

Locations

US (1); ZA (1)