Bacterial VaginosisPhase 2NCT02766023
LACTIN-V Study for Recurrent Bacterial Vaginosis
A Phase 2 study testing Lactobacillus crispatus CTV-05 and Metronidazole in people with Bacterial Vaginosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Bacterial Vaginosis
- What is being tested?
- Lactobacillus crispatus CTV-05 and Metronidazole
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 228 participants
- Where
- 4 sitesUnited States
- Study dates
- 3 Jun 2016to 11 Feb 2019
- 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 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 1. 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.
Who cannot join
- 1. 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Cook County Health and Hospitals System - Ruth M Rothstein CORE Center
Chicago, Illinois, 60612
University of California, San Diego - Antiviral Research Center
San Diego, California, 92103-8208
San Francisco General Hospital - Infectious Diseases
San Francisco, California, 94110-3518
Washington University School of Medicine in St. Louis - Infectious Disease Clinical Research Unit
St Louis, Missouri, 63110
About this study
Official title: Phase II-b Randomized Double-Blind Placebo-Controlled Trial of Lactobacillus Crispatus CTV-05 (LACTIN-V) to Prevent the Recurrence of Bacterial Vaginosis
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.
Read the detailed description
This is a Phase II-b multicenter randomized double-blind placebo-controlled trial to assess the efficacy of repeated doses of LACTIN-V compared to placebo in preventing BV recurrence in women diagnosed with BV. The study will also assess the safety of LACTIN-V by comparing the incidence of AEs between women randomized to LACTIN-V or placebo. The study plans to enroll 228 non-pregnant, pre-menopausal women age 18 to 45 years. Women will be randomized 2:1 to receive LACTIN-V or placebo. Potentially eligible women will start a standard 5-day course of MetroGel. Women will return to the study clinic within 2 days after completing the 5-day course of MetroGel to re-evaluate eligibility criteria and review the BV test results from the screening visit. Women with Amsel criteria > /=3 and Nugent score 4-10 will be instructed to administer the LACTIN-V or placebo at home for 5 consecutive days and then twice weekly for 10 weeks. The primary objectives of this study are: 1) To estimate the efficacy of repeated doses of LACTIN-V (2 x109 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. Secondary objectives are: 1) To investigate the colonization of LACTIN-V (presence of L. crispatus CTV-05 in the vaginal specimen) and fluctuations over 12 weeks, in relation to menses and sexual intercourse 2) To evaluate user acceptability and tolerability of LACTIN-V over 12 weeks, including perceptions around method of delivery and dosing. 3) To measure long-term colonization of LACTIN-V at 24 weeks (12 weeks after last dosing) 4) To estimate the long-term efficacy of repeated doses of LACTIN-V (2 x 109 cfu/dose) as compared to placebo in preventing BV recurrence at 24 weeks (12 weeks after last dosing)
- Conditions
- Bacterial Vaginosis
- Being tested
- Lactobacillus crispatus CTV-05, Metronidazole, Placebo
- Keywords
- CTV-05, LACTIN-V, Lactobacillus, MetroGel®, Vaginitis
- Medical subject headings
- Vaginosis, Bacterial, Vaginitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactobacillus crispatus CTV-05Biological
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.
MetronidazoleDrug
Metronidazole is a nitroimidazole. Metronidazole gel (MetroGel) is applied vaginally 7.5 mg/gm daily for 5 days
PlaceboOther
Placebo formulation applied vaginally, daily x 5 days then twice weekly x 10 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Metronidazole; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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."
Measured: 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.
Measured: 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.
A subject was considered compliant with the assigned study product if she took 4 of the first 5 daily doses and at least 75% of the scheduled doses overall prior to the first diagnosis of BV or through Week 12, whichever occurred first. Compliance was assessed by subject report via the memory aid and, separately, applicator staining of the returned kit. Compliance was assessed on a weekly basis and the time (week) at which the subject became non-compliant was determined by blinded PI review.
Measured: Day 1 to Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Categorical Variables on Likert Scale
Participants answered a detailed self-administered questionnaire at Week 12 assessing the acceptability of the study product and the applicator. Questionnaire items included rating aspects of the product and applicator by Likert-scale responses of strongly agree, agree, neutral, disagree and strongly disagree.
Measured: Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Likelihood to Use
Participants answered a detailed self-administered questionnaire at Week 12 assessing the acceptability of the study product and the applicator. Questionnaire items included rating aspects of the product and applicator by various measures, including the question, "If a non-antibiotic, clinically proven lactobacillus product were available for treatment and prevention of BV, what are the chances that you would use it?"
Measured: Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Current Partner's Reaction to the Product
Participants answered a detailed self-administered questionnaire at Week 12 assessing the acceptability of the study product and the applicator. Questionnaire items included rating aspects of the product and applicator by various measures, including "My current partner's reaction to the product was..." with the options as listed below.
Measured: Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Current Partner's Reaction as Influence
Participants answered a detailed self-administered questionnaire at Week 12 assessing the acceptability of the study product and the applicator. Questionnaire items included rating aspects of the product and applicator by various measures, including if their current partner's reaction to the product influenced their use of the product.
Measured: Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Experience Side Effects
Participants answered a detailed self-administered questionnaire at Week 12 assessing the acceptability of the study product and the applicator. Questionnaire items included rating aspects of the product and applicator by various measures, including a Yes/No question about experiencing side effects.
Measured: Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Experience of Side Effects Make Less Likely to Use
Participants answered a detailed self-administered questionnaire at Week 12 assessing the acceptability of the study product and the applicator. Questionnaire items included rating aspects of the product and applicator by various measures, including a Yes/No question about experiencing side effects. For those participants who answered Yes to experiencing side effects, a follow-up question asked "would these side effects make you less likely to use the product again?"
Measured: Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Continuous/Discrete Response Regarding Product
Participants answered a detailed self-administered questionnaire at Week 12 assessing the acceptability of the study product and the applicator. Questionnaire items included rating aspects of the product and applicator by various measures, including by rating factors on a 0-10 scale, with 0 being "not at all" and 10 being "extremely".
Measured: Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Continuous/Discrete Response Regarding Product Use
Participants answered a detailed self-administered questionnaire at Week 12 assessing the acceptability of the study product and the applicator. Questionnaire items included rating aspects of the product and applicator by various measures, including by rating factors on use of the product on a 0-10 scale, with 0 being "not at all" and 10 being "extremely so".
Measured: Day 84
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product in the LACTIN-V Arm Overall.
Colonization of L. crispatus was determined from the concentrations of L. crispatus species and L. crispatus CTV-05 obtained from qPCR. Successful colonization was defined as: If CTV-05 concentration was above the lower limit of detection (LLOD) and the L. crispatus was above the LLOD, then successful colonization had occurred. If either CTV-05 or L. crispatus concentration was below LLOD or indeterminate, then successful colonization had not occurred. The LLOD for CTV-05 was 660 copies/mL and the LLOD for L. crispatus was 953 copies/mL
Measured: Day 1 to Day 84
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Intercourse.
Colonization of L. crispatus was determined from the concentrations of L. crispatus species and L. crispatus CTV-05 obtained from qPCR. Successful colonization was defined as: If CTV-05 concentration was above the lower limit of detection (LLOD) and the L. crispatus was above the LLOD, then successful colonization had occurred. If either CTV-05 or L. crispatus concentration was below LLOD or indeterminate, then successful colonization had not occurred. The LLOD for CTV-05 was 660 copies/mL and the LLOD for L. crispatus was 953 copies/mL
Measured: Day 1
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Intercourse.
Colonization of L. crispatus was determined from the concentrations of L. crispatus species and L. crispatus CTV-05 obtained from qPCR. Successful colonization was defined as: If CTV-05 concentration was above the lower limit of detection (LLOD) and the L. crispatus was above the LLOD, then successful colonization had occurred. If either CTV-05 or L. crispatus concentration was below LLOD or indeterminate, then successful colonization had not occurred. The LLOD for CTV-05 was 660 copies/mL and the LLOD for L. crispatus was 953 copies/mL
Measured: Day 28
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Intercourse.
Colonization of L. crispatus was determined from the concentrations of L. crispatus species and L. crispatus CTV-05 obtained from qPCR. Successful colonization was defined as: If CTV-05 concentration was above the lower limit of detection (LLOD) and the L. crispatus was above the LLOD, then successful colonization had occurred. If either CTV-05 or L. crispatus concentration was below LLOD or indeterminate, then successful colonization had not occurred. The LLOD for CTV-05 was 660 copies/mL and the LLOD for L. crispatus was 953 copies/mL
Measured: Day 56
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Intercourse.
Colonization of L. crispatus was determined from the concentrations of L. crispatus species and L. crispatus CTV-05 obtained from qPCR. Successful colonization was defined as: If CTV-05 concentration was above the lower limit of detection (LLOD) and the L. crispatus was above the LLOD, then successful colonization had occurred. If either CTV-05 or L. crispatus concentration was below LLOD or indeterminate, then successful colonization had not occurred. The LLOD for CTV-05 was 660 copies/mL and the LLOD for L. crispatus was 953 copies/mL
Measured: Day 84
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Menses.
Colonization of L. crispatus was determined from the concentrations of L. crispatus species and L. crispatus CTV-05 obtained from qPCR. Successful colonization was defined as: If CTV-05 concentration was above the lower limit of detection (LLOD) and the L. crispatus was above the LLOD, then successful colonization had occurred. If either CTV-05 or L. crispatus concentration was below LLOD or indeterminate, then successful colonization had not occurred. The LLOD for CTV-05 was 660 copies/mL and the LLOD for L. crispatus was 953 copies/mL
Measured: Day 28
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Menses.
Colonization of L. crispatus was determined from the concentrations of L. crispatus species and L. crispatus CTV-05 obtained from qPCR. Successful colonization was defined as: If CTV-05 concentration was above the lower limit of detection (LLOD) and the L. crispatus was above the LLOD, then successful colonization had occurred. If either CTV-05 or L. crispatus concentration was below LLOD or indeterminate, then successful colonization had not occurred. The LLOD for CTV-05 was 660 copies/mL and the LLOD for L. crispatus was 953 copies/mL
Measured: Day 56
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Menses.
Colonization of L. crispatus was determined from the concentrations of L. crispatus species and L. crispatus CTV-05 obtained from qPCR. Successful colonization was defined as: If CTV-05 concentration was above the lower limit of detection (LLOD) and the L. crispatus was above the LLOD, then successful colonization had occurred. If either CTV-05 or L. crispatus concentration was below LLOD or indeterminate, then successful colonization had not occurred. The LLOD for CTV-05 was 660 copies/mL and the LLOD for L. crispatus was 953 copies/mL
Measured: Day 84
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product Overall.
Colonization of L. crispatus was determined from the concentrations of L. crispatus species and L. crispatus CTV-05 obtained from qPCR. Successful colonization was defined as: If CTV-05 concentration was above the lower limit of detection (LLOD) and the L. crispatus was above the LLOD, then successful colonization had occurred. If either CTV-05 or L. crispatus concentration was below LLOD or indeterminate, then successful colonization had not occurred. The LLOD for CTV-05 was 660 copies/mL and the LLOD for L. crispatus was 953 copies/mL
Measured: 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 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 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. All BV diagnoses following 15 days after enrollment (22 days after commencement of MetroGel treatment) were considered a recurrent episode.
Measured: Day 1 to Day 168
The Number of Participants Who Discontinued Study Product Early in Each Study Arm Due to Adverse Events.
Tolerability of LACTIN-V and the applicator was measured by the proportion of participants who discontinued the study product prior to completing the dose schedule due to an adverse event.
Measured: Day 1 to Day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2016 (estimated)
- Study start3 Jun 2016
- Primary completion11 Feb 2019
- Study completion11 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Bacterial VaginosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 228 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02766023
- Sponsor's protocol ID
- 14-0029
- Other IDs
- HHSN272201300014I
- Status last verified
- 5 Apr 2017
- First submitted
- 21 Apr 2016
- Last updated
- 4 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Liu R, Armstrong E, Hemmerling A, Miller S, Huibner S, Lagenaur L, Parks TP, Cohen CR, Coburn B, Kaul R. Vaginal microbe-binding antibody interactions with a Lactobacillus crispatus live biotherapeutic following treatment for bacterial vaginosis. Microbiol Spectr. 2026 Sep 1:e0398325. doi: 10.1128/spectrum.03983-25. Online ahead of print.
PubMed 42678149Armstrong 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.
PubMed 35113809Cohen 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.
PubMed 32402161
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II-b Randomized Double-Blind Placebo-Controlled Trial of Lactobacillus Crispatus CTV-05 (LACTIN-V) to Prevent the Recurrence of Bacterial Vaginosis
- ClinicalTrials.gov ID
- NCT02766023
- Acronym / sponsor ID
- 14-0029
- Conditions
- Bacterial Vaginosis
- Keywords
- CTV-05, LACTIN-V, Lactobacillus, MetroGel®, Vaginitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 228 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 3 Jun 2016 (actual)
- Primary completion
- 11 Feb 2019 (actual)
- Study completion
- 11 Feb 2019 (actual)
- First posted
- 9 May 2016 (estimated)
- Results
- Posted 11 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a Phase II-b multicenter randomized double-blind placebo-controlled trial to assess the efficacy of repeated doses of LACTIN-V compared to placebo in preventing BV recurrence in women diagnosed with BV. The study will also assess the safety of LACTIN-V by comparing the incidence of AEs between women randomized to LACTIN-V or placebo. The study plans to enroll 228 non-pregnant, pre-menopausal women age 18 to 45 years. Women will be randomized 2:1 to receive LACTIN-V or placebo. Potentially eligible women will start a standard 5-day course of MetroGel. Women will return to the study clinic within 2 days after completing the 5-day course of MetroGel to re-evaluate eligibility criteria and review the BV test results from the screening visit. Women with Amsel criteria > /=3 and Nugent score 4-10 will be instructed to administer the LACTIN-V or placebo at home for 5 consecutive days and then twice weekly for 10 weeks. The primary objectives of this study are: 1) To estimate the efficacy of repeated doses of LACTIN-V (2 x109 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. Secondary objectives are: 1) To investigate the colonization of LACTIN-V (presence of L. crispatus CTV-05 in the vaginal specimen) and fluctuations over 12 weeks, in relation to menses and sexual intercourse 2) To evaluate user acceptability and tolerability of LACTIN-V over 12 weeks, including perceptions around method of delivery and dosing. 3) To measure long-term colonization of LACTIN-V at 24 weeks (12 weeks after last dosing) 4) To estimate the long-term efficacy of repeated doses of LACTIN-V (2 x 109 cfu/dose) as compared to placebo in preventing BV recurrence at 24 weeks (12 weeks after last dosing)
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LACTIN-V | Experimental | Biological: Lactobacillus crispatus CTV-05, Drug: MetronidazoleSubjects 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 |
| Placebo | Placebo comparator | Drug: Metronidazole, Other: PlaceboSubjects 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 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 1. 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.
Key exclusion criteria (1 listed)
- 1. 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lactobacillus crispatus CTV-05LACTIN-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. | Biological | LACTIN-V |
| MetronidazoleMetronidazole is a nitroimidazole. Metronidazole gel (MetroGel) is applied vaginally 7.5 mg/gm daily for 5 days | Drug | LACTIN-V, Placebo |
| PlaceboPlacebo formulation applied vaginally, daily x 5 days then twice weekly x 10 weeks. | Other | Placebo |
Primary outcome
The Proportion of Participants Reporting Product-related Adverse Events (AEs) and Serious Adverse Events (SAEs) in Each Study Arm.
Time frame: Day 1 to Day 168
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."
The Proportion of Participants With a Positive BV Diagnosis in Each Study Arm.
Time frame: Day 1 to Day 84
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.
20 secondary outcomes
The Proportion of Participants Who Are Compliant With the Complete Dose Regimen as Assessed by Participant Reporting and Applicator Staining.
Time frame: Day 1 to Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Categorical Variables on Likert Scale
Time frame: Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Likelihood to Use
Time frame: Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Current Partner's Reaction to the Product
Time frame: Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Current Partner's Reaction as Influence
Time frame: Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Experience Side Effects
Time frame: Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Experience of Side Effects Make Less Likely to Use
Time frame: Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Continuous/Discrete Response Regarding Product
Time frame: Day 84
Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Continuous/Discrete Response Regarding Product Use
Time frame: Day 84
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product in the LACTIN-V Arm Overall.
Time frame: Day 1 to Day 84
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Intercourse.
Time frame: Day 1
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Intercourse.
Time frame: Day 28
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Intercourse.
Time frame: Day 56
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Intercourse.
Time frame: Day 84
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Menses.
Time frame: Day 28
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Menses.
Time frame: Day 56
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Menses.
Time frame: Day 84
The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product Overall.
Time frame: Day 1 to Day 168
The Proportion of Participants With a Positive BV Diagnosis in Each Study Arm.
Time frame: Day 1 to Day 168
The Number of Participants Who Discontinued Study Product Early in Each Study Arm Due to Adverse Events.
Time frame: Day 1 to Day 84
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42678149Liu R, Armstrong E, Hemmerling A, Miller S, Huibner S, Lagenaur L, Parks TP, Cohen CR, Coburn B, Kaul R. Vaginal microbe-binding antibody interactions with a Lactobacillus crispatus live biotherapeutic following treatment for bacterial vaginosis. Microbiol Spectr. 2026 Sep 1:e0398325. doi: 10.1128/spectrum.03983-25. Online ahead of print.
- Derived from this study: PubMed 35113809Armstrong 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.
- Derived from this study: PubMed 32402161Cohen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lactobacillus crispatus CTV-05 and Metronidazole 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 1 inclusion and 1 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 4 Mar 2020. 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 11 Feb 2020). 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?
The Proportion of Participants Reporting Product-related Adverse Events (AEs) and Serious Adverse Events (SAEs) in Each Study Arm. (time frame: Day 1 to Day 168). The study lists 2 primary outcomes in all. 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 NCT02766023, which also lists 3 linked publications.
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 4 Mar 2020.