LACTIN-V Study for Recurrent Bacterial Vaginosis

NCT02766023 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 14-0029HHSN272201300014I
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 4

Brief Summary

This Phase 2b trial is designed to provide a screening evaluation for the hypothesis that, following a 5-day treatment with MetroGel® to treat BV, L. crispatus CTV-05 (LACTIN-V, Osel, Inc.) administered at 2 x 10\^9 cfu/dose using a vaginal applicator reduces the 12-week incidence of BV recurrence when compared to placebo. The primary objectives of this study are: 1) To estimate the efficacy of repeated doses of LACTIN-V (2 x 10\^9 cfu/dose) as compared to placebo in preventing BV recurrence by 12 weeks following treatment of BV with MetroGel vaginal gel (MetroGel). 2) To assess the safety of LACTIN-V over 24 weeks by comparing the incidence of AEs between individuals randomized to LACTIN-V or placebo.

Conditions

Bacterial Vaginosis

Keywords

CTV-05; LACTIN-V; Lactobacillus; MetroGel®; Vaginitis

Outcome Measures

Primary Outcomes (2)

• The Proportion of Participants Reporting Product-related Adverse Events (AEs) and Serious Adverse Events (SAEs) in Each Study Arm.

  Adverse events and serious adverse events were collected during the entire study period. Relatedness to study product was assessed by the site investigator according to the protocol definition of related as "There is a reasonable possibility that the study product caused the AE. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the AE."

  Day 1 to Day 168

• The Proportion of Participants With a Positive BV Diagnosis in Each Study Arm.

  A positive BV diagnosis was defined by meeting at least 3 of the 4 Amsel criteria and a Nugent score of 4-10. Amsel criteria are: homogeneous, thin, grayish-white discharge that smoothly coats the vaginal walls; vaginal pH \>4.5; positive whiff-amine test, defined as the presence of a fishy odor when a drop of 10% potassium hydroxide is added to a sample of vaginal discharge; and presence of clue cells (\>20%) on microscopy. The Amsel score ranges from 0-4, where higher scores mean a worse outcome. The Nugent score is calculated by assessing for the presence of large Gram-positive rods scored as 0 to 4, small Gram-variable rods scored as 0 to 4, and curved Gram-variable rods scored as 0 to 2, and adding all component scores. The Nugent score ranges from 0-10, where higher scores mean a worse outcome. All BV diagnoses following 15 days after enrollment (22 days after commencement of MetroGel treatment) were considered a recurrent episode.

  Day 1 to Day 84

Secondary Outcomes (20)

• The Proportion of Participants Who Are Compliant With the Complete Dose Regimen as Assessed by Participant Reporting and Applicator Staining.

  Day 1 to Day 84

• Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Categorical Variables on Likert Scale

  Day 84

• Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Likelihood to Use

  Day 84

• Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Current Partner's Reaction to the Product

  Day 84

• Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Current Partner's Reaction as Influence

  Day 84

Study Arms (2)

LACTIN-V

EXPERIMENTAL

Subjects receive 5-day course of metronidazole gel 7.5 mg/gm daily applied vaginally. Subjects then receive LACTIN-V 2x10\^9 cfu/dose applied vaginally for 5 days then twice weekly for 10 weeks. N=152

Biological: Lactobacillus crispatus CTV-05; Drug: Metronidazole

Placebo

PLACEBO COMPARATOR

Subjects receive 5-day course of metronidazole gel 7.5 mg/gm daily applied vaginally. Subjects then receive placebo applied vaginally for 5 days then twice weekly for 10 weeks. N=76

Drug: Metronidazole; Other: Placebo

Interventions

Lactobacillus crispatus CTV-05 BIOLOGICAL

LACTIN-V is an intravaginal live biotherapeutic product composed of Lactobacillus crispatus CTV-05 (LACTIN-V, Osel Inc) in a vaginal applicator. Subjects receive 2x10\^9 cfu/dose applied vaginally daily x 5 days then twice weekly x 10 weeks.

LACTIN-V

Metronidazole DRUG

Metronidazole is a nitroimidazole. Metronidazole gel (MetroGel) is applied vaginally 7.5 mg/gm daily for 5 days

LACTIN-V; Placebo

Placebo OTHER

Placebo formulation applied vaginally, daily x 5 days then twice weekly x 10 weeks.

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \. Capable of reading and writing English and voluntarily provide written informed consent to participate in the study and comply with all study procedures 2. Untreated BV (asymptomatic or symptomatic) as diagnosed during the screening visit defined by \>/=3 Amsel criteria. Note: Amsel criteria include the following: --Homogeneous, thin, grayish-white discharge that smoothly coats the vaginal walls; --Vaginal pH \>4.5; --Positive whiff-amine test, defined as the presence of a fishy odor when a drop of 10% potassium hydroxide (KOH) is added to a sample of vaginal discharge; --Presence of clue cells (\>20% on microscopy). 3. Untreated BV(asymptomatic or symptomatic) as confirmed in the laboratory using the Nugent scoring system (Nugent Score \>/= 4) 4. Otherwise healthy pre-menopausal women 18-45 years of age on the day of screening 5. Regular predictable menstrual cycles or amenorrheic for at least 3 months due to use of a long-acting progestin or continuous use of oral contraceptives 6. Willing to be asked questions about personal medical health and sexual history. 7. Willing to apply study agent vaginally and comply with study examinations. 8. Agree to abstain from sexual intercourse during the first 5 consecutive days of study product administration, 12 hours prior to study visits and for 12 hours after each study product application 9. Agree to abstain from the use of any other intravaginal product throughout the trial period from the time of screening through Visit 7 (Week 24, Day 168) Note: Intravaginal products include contraceptive creams such as Gynol II, gels, foams, sponges, lubricants not approved by the study investigators, and douches. Limit use of tampons during menstruation to unscented products. 10. Must be of non-childbearing potential or if of childbearing potential, must agree to use a reliable method of birth control for the duration of the study Note: Reliable methods of birth control include tubal ligation, male partner with a vasectomy, a steroidal contraceptive (oral, patch, injectable or implantable), IUD, condoms or abstinence.

You may not qualify if:

• \. Urogenital infection at screening Note: Urogenital infection includes urinary tract infection, Trichomonas (T.) vaginalis, Neisseria (N.) gonorrhoeae, Chlamydia (C.) trachomatis, Treponema (T.) pallidum, or vulvo-vaginal candidiasis. 2. Diagnosis of two or more outbreaks of N. gonorrhoeae, C. trachomatis, T. pallidum, T. vaginalis, or herpes simplex virus (herpes genitalis) within 6 months prior to screening 3. Positive for syphilis or HIV at screening 4. Current pregnancy or within 2 months of last pregnancy and/or currently breastfeeding\*\*. Criteria will be assessed at screening and enrollment. 5. Vaginal or systemic antibiotic or antifungal therapy (other than MetroGel given as part of study procedures) within 21 days of screening or within 30 days of enrollment\*\* 6. Use of disulfiram within past 2 weeks or other contraindication to use of MetroGel\*\* 7. Any condition requiring regular periodic use of systemic antibiotics during participation in the trial 8. Active genital herpes lesion\*\* (if not resolved by enrollment)\*\* 9. Investigational drug use other than LACTIN-V within 30 days or 10 half-lives of the drug, whichever is longer, of enrollment visit\*\* 10. Other planned participation in an investigational drug study while participating in this study\*\* 11. Menopause defined as more than 12 consecutive months of amenorrhea without another known cause including pregnancy 12. IUD insertion or removal, pelvic surgery, cervical cryotherapy or cervical laser treatment within the last 2 months prior to screening 13. Use of vaginal ring (eg, NuvaRing) within 3 days of screening or during the course of the study\*\* 14. Failure to complete 5 days of MetroGel with the last dose taken no later than 48 hours prior to randomization\*\*\* 15. Use of new long-acting hormonal treatments. Participant may be enrolled if stable (\>3 months) on existing therapy as determined by the principal investigator\*\* 16. Known allergy to any component of LACTIN-V/placebo or MetroGel or to nitroimidazole derivatives or latex (condoms) 17. Any social, medical, or psychiatric condition, including history of drug or alcohol abuse that in the opinion of the investigator would make it unlikely for the participant to comply with the study \*\* Note: Criteria will be assessed at screening and enrollment. \*\*\*Note: Criteria will be assessed at enrollment

Sponsors & Collaborators

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

Study Sites (4)

University of California, San Diego - Antiviral Research Center

San Diego, California, 92103-8208, United States

Location

San Francisco General Hospital - Infectious Diseases

San Francisco, California, 94110-3518, United States

Location

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

Chicago, Illinois, 60612, United States

Location

Washington University School of Medicine in St. Louis - Infectious Disease Clinical Research Unit

St Louis, Missouri, 63110, United States

Location

Related Publications (2)

• Armstrong E, Hemmerling A, Miller S, Burke KE, Newmann SJ, Morris SR, Reno H, Huibner S, Kulikova M, Liu R, Crawford ED, Castaneda GR, Nagelkerke N, Coburn B, Cohen CR, Kaul R. Metronidazole treatment rapidly reduces genital inflammation through effects on bacterial vaginosis-associated bacteria rather than lactobacilli. J Clin Invest. 2022 Mar 15;132(6):e152930. doi: 10.1172/JCI152930.

  PMID: 35113809 DERIVED

• Cohen CR, Wierzbicki MR, French AL, Morris S, Newmann S, Reno H, Green L, Miller S, Powell J, Parks T, Hemmerling A. Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis. N Engl J Med. 2020 May 14;382(20):1906-1915. doi: 10.1056/NEJMoa1915254.

  PMID: 32402161 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

Results Point of Contact

• Title: Craig Cohen, MD, MPH
• Organization: University of California San Francisco

Craig.Cohen@ucsf.edu

(415) 476-5874

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: April 21, 2016
• First Posted: May 9, 2016
• Study Start: June 3, 2016
• Primary Completion: February 11, 2019
• Study Completion: February 11, 2019
• Last Updated: March 4, 2020
• Results First Posted: February 11, 2020

Record last verified: 2017-04-05

Locations

US (4)