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Phase 2 Trial of LACTIN-V in Women at High Risk of HIV Acquisition

Primary Purpose

Bacterial Vaginosis, HIV Infections

Status
Unknown status
Phase
Phase 2
Locations
South Africa
Study Type
Interventional
Intervention
LACTIN-V
Placebo
Sponsored by
Osel, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Bacterial Vaginosis focused on measuring Vaginal microbiome, bacterial Vaginosis, HIV infections

Eligibility Criteria

18 Years - 23 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. FRESH study participant.
  2. Capable of reading and writing English or isiZulu and voluntarily provide written informed consent to participate in the study and comply with all study procedures
  3. HIV-negative
  4. Nugent score 4-10 on vaginal Gram stain
  5. Otherwise healthy women, 18-23 years of age on the day of enrolment
  6. Regular predictable menstrual cycles or amenorrhoeic for at least 3 months due to use of a long-acting progestin.
  7. Willing to complete 7-day course of oral metronidazole.
  8. Willing to be asked questions about personal medical health and sexual history
  9. Willing to apply study agent vaginally and comply with study examinations
  10. Willing to self-administer Study Product on dosing days that do not coincide with regular FRESH study visits.
  11. Agree to try to abstain from sexual intercourse 12 hours prior to study visits that include a gynaecological exam (Randomization Visit 3, Follow-up Visit 11, Final Visit 19).
  12. Agree to try to abstain from sexual intercourse for 12 hours after study product administration to ensure that the product will remain inside the vagina.

  13. Agree to abstain from the use of any other vaginal product throughout the trial period from the time of enrolment through the end of the study.

    Note: Intravaginal products include contraceptive creams such as Gynol II, gels, foams, sponges, lubricants not approved by the study investigators, tampons and douches.

  14. Must be stable on a reliable method of long-acting birth control and agree to remain on, for the duration of the study (if of childbearing potential) or, of non-childbearing potential (permanently sterile).

Exclusion Criteria:

  1. Urogenital infection (as tested during the FRESH Week 5 Study Visit, reported within 30 days of detection at the LACTIN-V Enrolment Visit).

    Note: Urogenital infection includes urinary tract infection, Trichomonas (T.) vaginalis, Neisseria (N.) gonorrhoeae, Chlamydia (C.) trachomatis, Mycoplasma genitalium.

  2. Diagnosis of two or more outbreaks of N. gonorrhoeae, C. trachomatis, T. vaginalis, Mycoplasma genitalium, or herpes simplex virus (herpes genitalis) within 6 months prior to enrolment.
  3. Subject is ineligible if menstrual cycle length is less than 21 days
  4. Subject is ineligible if deep epithelial disruption is observed on genital examination noted on or before the Randomization Visit
  5. Positive for HIV (as tested during the FRESH Week 5 Study Visit, within 30 days of the LACTIN-V Enrolment Visit).
  6. Current pregnancy or within 2 months of last pregnancy
  7. Vaginal or systemic antibiotic or antifungal therapy within 21 days of enrolment
  8. Use of disulfiram within past 2 weeks or other contraindication to use of metronidazole
  9. Any condition requiring regular periodic use of systemic antibiotics during participation in the trial
  10. Investigational drug use other than LACTIN-V within 30 days or 10 half- lives of the drug, whichever is longer, of Enrolment Visit
  11. Other planned participation in an investigational drug study while participating in this study
  12. Intrauterine device (IUD) insertion or removal, pelvic surgery, cervical cryotherapy or cervical laser treatment within the last 2 months prior to enrolment
  13. Use of vaginal ring (e.g, NuvaRing) within 3 days of enrolment or during the course of the study
  14. Hysterectomy
  15. Unwilling to complete 7 days of oral metronidazole (twice daily) with the last dose taken no later than 48 hours prior to randomization (minimum of 12 of 14 doses required)
  16. Use of new long-acting hormonal treatments. Participant may be enrolled if stable (>1 month) on existing therapy as determined by the principal investigator (PI)
  17. Known allergy to any component of LACTIN-V/placebo or metronidazole or to nitroimidazole derivatives or latex (condoms)
  18. Any social, medical, or psychiatric condition including history of drug or alcohol abuse that in the opinion of the investigator would make it difficult for the participant to comply with study procedures
  19. Any serious or chronic illness, deemed incompatible with study participation by the study doctor, including immunosuppression due to cancer chemotherapy, systemic corticosteroids.

Sites / Locations

  • FRESH (Females Rising through Education, Support and Health) Clinical Research SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

LACTIN-V

Placebo

Arm Description

LACTIN-V contains a naturally occurring human vaginal strain of Lactobacillus (L.) crispatus CTV- 05. At a potency of 2 x 109 cfu/dose, it is preserved in powder formulation, and applied by a vaginal applicator. Women will receive the study product for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.

A matching placebo formulation without L. crispatus CTV-05 is supplied in an identical applicator containing just the powder formulation. Women will receive the placebo for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.

Outcomes

Primary Outcome Measures

Determine the effect of repeat dosing of LACTIN-V (2 x 109 cfu/dose) on genital tract inflammation in young South African women at risk of HIV.
The proportion of participants with decreased genital tract proinflammatory cytokines and HIV target cells over 64 days of follow up, compared to levels at baseline Our outcome will be a change in immune parameters after treatment with LACTIN-V in comparison to placebo (proinflammatory cytokines in genital fluid, activated endocervical HIV target cells and the anti-HIV effect of vaginal secretions).
Determine the ability of LACTIN-V to promote a Lactobacillus-dominant vaginal microbiota in young South African women at risk of HIV.
The proportion of participants with increased Lactobacillus-dominant vaginal microbiota in young South African women, compared to levels at randomization (Day 8) after completion of metronidazole. Measured will be overall Lactobacillus species, as well as Lactobacillus crispatus, Lactobacillus jensenii, Lactobacillus gasseri, and Lactobacillus iners. Our primary outcome is the presence of Lactobacillus-dominant vaginal microbial cervico-types after 4 weeks of treatment with LACTIN-V, and following the post- dosing phase at Day 64.
Determine the ability of LACTIN-V for vaginal colonization of L. crispatus CTV-05 in young South African women at risk of HIV.
The proportion of participants experiencing successful colonization with L. crispatus CTV-05 following dose of study product through the final visit (Day 64) in the LACTIN-V arm.
Determine the ability of LACTIN-V for preventing bacterial vaginosis in young South African women at risk of HIV.
The proportion of participants with a positive Bacterial Vaginosis (BV) diagnosis in each study arm by Day 64.
Determine the safety of LACTIN-V in a population of young South African women at risk for HIV.
Safety of LACTIN-V and the applicator will be measured by: The proportion of participants reporting product-related Adverse Events (AEs) and Serious Adverse Events (SAEs) through the final visit that are likely related to use of study product compared by study arm, in particular Grade 3 AEs and SAEs.
Determine the acceptability of LACTIN-V in a population of young South African women at risk for HIV.
Acceptability of LACTIN-V and the applicator will be measured by standardized questionnaire about acceptability of the study product and participants' stated willingness to use this type of product in the future, in each study arm.

Secondary Outcome Measures

Full Information

First Posted
May 7, 2021
Last Updated
August 19, 2021
Sponsor
Osel, Inc.
Collaborators
University of California, San Francisco, University of KwaZulu, Harvard University, Aurum Institute, Health Systems Trust
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1. Study Identification

Unique Protocol Identification Number
NCT05022212
Brief Title
Phase 2 Trial of LACTIN-V in Women at High Risk of HIV Acquisition
Official Title
Phase 2 Placebo-controlled Randomized Trial of LACTIN-V (Lactobacillus Crispatus CTV-05) Among Women at High Risk of HIV Acquisition in Durban, South Africa
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Unknown status
Study Start Date
May 10, 2021 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
March 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Osel, Inc.
Collaborators
University of California, San Francisco, University of KwaZulu, Harvard University, Aurum Institute, Health Systems Trust

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to assess the impact of LACTIN-V, a vaginally administered live biotherapeutic product (LBP) that contains the human L. crispatus CTV-05 strain, on the vaginal microbiome of Lactobacillus-deficient young women in the South African FRESH study who are at high risk for HIV acquisition.
Detailed Description
We will conduct a randomized, placebo-controlled trial of the vaginal live biotherapeutic product LACTIN-V in 60 young South African women. After being informed about the study and potential risks, all participants giving written informed consent will be enrolled if they meet eligibility criteria. At enrollment on Day 1, they will start a 7-day course of standard oral metronidazole treatment for bacterial vaginosis. Women who completed their metronidazole treatment will be randomized 2:1 to LACTIN-V vs. placebo. Within 8-48 hours of the final metronidazole dose, women will receive the study product for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bacterial Vaginosis, HIV Infections
Keywords
Vaginal microbiome, bacterial Vaginosis, HIV infections

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
We will conduct a randomized, placebo-controlled trial of the vaginal live biotherapeutic product LACTIN-V in 60 young South African women, randomizing women 2:1 to LACTIN-V vs. placebo.
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
LACTIN-V
Arm Type
Active Comparator
Arm Description
LACTIN-V contains a naturally occurring human vaginal strain of Lactobacillus (L.) crispatus CTV- 05. At a potency of 2 x 109 cfu/dose, it is preserved in powder formulation, and applied by a vaginal applicator. Women will receive the study product for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
A matching placebo formulation without L. crispatus CTV-05 is supplied in an identical applicator containing just the powder formulation. Women will receive the placebo for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
Intervention Type
Drug
Intervention Name(s)
LACTIN-V
Other Intervention Name(s)
Lactobacillus crispatus CTV-05
Intervention Description
administered vaginally
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
administered vaginally
Primary Outcome Measure Information:
Title
Determine the effect of repeat dosing of LACTIN-V (2 x 109 cfu/dose) on genital tract inflammation in young South African women at risk of HIV.
Description
The proportion of participants with decreased genital tract proinflammatory cytokines and HIV target cells over 64 days of follow up, compared to levels at baseline Our outcome will be a change in immune parameters after treatment with LACTIN-V in comparison to placebo (proinflammatory cytokines in genital fluid, activated endocervical HIV target cells and the anti-HIV effect of vaginal secretions).
Time Frame
over 64 days
Title
Determine the ability of LACTIN-V to promote a Lactobacillus-dominant vaginal microbiota in young South African women at risk of HIV.
Description
The proportion of participants with increased Lactobacillus-dominant vaginal microbiota in young South African women, compared to levels at randomization (Day 8) after completion of metronidazole. Measured will be overall Lactobacillus species, as well as Lactobacillus crispatus, Lactobacillus jensenii, Lactobacillus gasseri, and Lactobacillus iners. Our primary outcome is the presence of Lactobacillus-dominant vaginal microbial cervico-types after 4 weeks of treatment with LACTIN-V, and following the post- dosing phase at Day 64.
Time Frame
over 64 days
Title
Determine the ability of LACTIN-V for vaginal colonization of L. crispatus CTV-05 in young South African women at risk of HIV.
Description
The proportion of participants experiencing successful colonization with L. crispatus CTV-05 following dose of study product through the final visit (Day 64) in the LACTIN-V arm.
Time Frame
over 64 days
Title
Determine the ability of LACTIN-V for preventing bacterial vaginosis in young South African women at risk of HIV.
Description
The proportion of participants with a positive Bacterial Vaginosis (BV) diagnosis in each study arm by Day 64.
Time Frame
over 64 days
Title
Determine the safety of LACTIN-V in a population of young South African women at risk for HIV.
Description
Safety of LACTIN-V and the applicator will be measured by: The proportion of participants reporting product-related Adverse Events (AEs) and Serious Adverse Events (SAEs) through the final visit that are likely related to use of study product compared by study arm, in particular Grade 3 AEs and SAEs.
Time Frame
over 64 days
Title
Determine the acceptability of LACTIN-V in a population of young South African women at risk for HIV.
Description
Acceptability of LACTIN-V and the applicator will be measured by standardized questionnaire about acceptability of the study product and participants' stated willingness to use this type of product in the future, in each study arm.
Time Frame
over 64 days

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
23 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: FRESH study participant. Capable of reading and writing English or isiZulu and voluntarily provide written informed consent to participate in the study and comply with all study procedures HIV-negative Nugent score 4-10 on vaginal Gram stain Otherwise healthy women, 18-23 years of age on the day of enrolment Regular predictable menstrual cycles or amenorrhoeic for at least 3 months due to use of a long-acting progestin. Willing to complete 7-day course of oral metronidazole. Willing to be asked questions about personal medical health and sexual history Willing to apply study agent vaginally and comply with study examinations Willing to self-administer Study Product on dosing days that do not coincide with regular FRESH study visits. Agree to try to abstain from sexual intercourse 12 hours prior to study visits that include a gynaecological exam (Randomization Visit 3, Follow-up Visit 11, Final Visit 19). Agree to try to abstain from sexual intercourse for 12 hours after study product administration to ensure that the product will remain inside the vagina. Agree to abstain from the use of any other vaginal product throughout the trial period from the time of enrolment through the end of the study. Note: Intravaginal products include contraceptive creams such as Gynol II, gels, foams, sponges, lubricants not approved by the study investigators, tampons and douches. Must be stable on a reliable method of long-acting birth control and agree to remain on, for the duration of the study (if of childbearing potential) or, of non-childbearing potential (permanently sterile). Exclusion Criteria: Urogenital infection (as tested during the FRESH Week 5 Study Visit, reported within 30 days of detection at the LACTIN-V Enrolment Visit). Note: Urogenital infection includes urinary tract infection, Trichomonas (T.) vaginalis, Neisseria (N.) gonorrhoeae, Chlamydia (C.) trachomatis, Mycoplasma genitalium. Diagnosis of two or more outbreaks of N. gonorrhoeae, C. trachomatis, T. vaginalis, Mycoplasma genitalium, or herpes simplex virus (herpes genitalis) within 6 months prior to enrolment. Subject is ineligible if menstrual cycle length is less than 21 days Subject is ineligible if deep epithelial disruption is observed on genital examination noted on or before the Randomization Visit Positive for HIV (as tested during the FRESH Week 5 Study Visit, within 30 days of the LACTIN-V Enrolment Visit). Current pregnancy or within 2 months of last pregnancy Vaginal or systemic antibiotic or antifungal therapy within 21 days of enrolment Use of disulfiram within past 2 weeks or other contraindication to use of metronidazole Any condition requiring regular periodic use of systemic antibiotics during participation in the trial Investigational drug use other than LACTIN-V within 30 days or 10 half- lives of the drug, whichever is longer, of Enrolment Visit Other planned participation in an investigational drug study while participating in this study Intrauterine device (IUD) insertion or removal, pelvic surgery, cervical cryotherapy or cervical laser treatment within the last 2 months prior to enrolment Use of vaginal ring (e.g, NuvaRing) within 3 days of enrolment or during the course of the study Hysterectomy Unwilling to complete 7 days of oral metronidazole (twice daily) with the last dose taken no later than 48 hours prior to randomization (minimum of 12 of 14 doses required) Use of new long-acting hormonal treatments. Participant may be enrolled if stable (>1 month) on existing therapy as determined by the principal investigator (PI) Known allergy to any component of LACTIN-V/placebo or metronidazole or to nitroimidazole derivatives or latex (condoms) Any social, medical, or psychiatric condition including history of drug or alcohol abuse that in the opinion of the investigator would make it difficult for the participant to comply with study procedures Any serious or chronic illness, deemed incompatible with study participation by the study doctor, including immunosuppression due to cancer chemotherapy, systemic corticosteroids.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Craig R Cohen, MD MPH
Phone
(415) 476-5874
Email
craig.cohen@ucsf.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Anke Hemmerling, MD PhD MPH
Phone
(510)717-0845
Email
anke.hemmerling@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Craig R Cohen, MD MPH
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
FRESH (Females Rising through Education, Support and Health) Clinical Research Site
City
Durban
State/Province
KwaZulu-Natal
ZIP/Postal Code
4066
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vaneshree Govender, MBBCh
Phone
+27 (0) 84 759 6461
Email
VGovender@auruminstitute.org
First Name & Middle Initial & Last Name & Degree
Krista Dong, MD
Phone
+27 (0) 31 906 0394
Email
kdong@mgh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Vaneshree Govender, MBBCh
First Name & Middle Initial & Last Name & Degree
Krista Dong, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28087240
Citation
Gosmann C, Anahtar MN, Handley SA, Farcasanu M, Abu-Ali G, Bowman BA, Padavattan N, Desai C, Droit L, Moodley A, Dong M, Chen Y, Ismail N, Ndung'u T, Ghebremichael MS, Wesemann DR, Mitchell C, Dong KL, Huttenhower C, Walker BD, Virgin HW, Kwon DS. Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women. Immunity. 2017 Jan 17;46(1):29-37. doi: 10.1016/j.immuni.2016.12.013. Epub 2017 Jan 10.
Results Reference
result
PubMed Identifier
22693410
Citation
Mitchell C, Manhart LE, Thomas K, Fiedler T, Fredricks DN, Marrazzo J. Behavioral predictors of colonization with Lactobacillus crispatus or Lactobacillus jensenii after treatment for bacterial vaginosis: a cohort study. Infect Dis Obstet Gynecol. 2012;2012:706540. doi: 10.1155/2012/706540. Epub 2012 May 30.
Results Reference
result
PubMed Identifier
32402161
Citation
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.
Results Reference
result
PubMed Identifier
19543144
Citation
Hemmerling A, Harrison W, Schroeder A, Park J, Korn A, Shiboski S, Cohen CR. Phase 1 dose-ranging safety trial of Lactobacillus crispatus CTV-05 for the prevention of bacterial vaginosis. Sex Transm Dis. 2009 Sep;36(9):564-9. doi: 10.1097/OLQ.0b013e3181a74924.
Results Reference
result
PubMed Identifier
20644497
Citation
Hemmerling A, Harrison W, Schroeder A, Park J, Korn A, Shiboski S, Foster-Rosales A, Cohen CR. Phase 2a study assessing colonization efficiency, safety, and acceptability of Lactobacillus crispatus CTV-05 in women with bacterial vaginosis. Sex Transm Dis. 2010 Dec;37(12):745-50. doi: 10.1097/OLQ.0b013e3181e50026.
Results Reference
result
PubMed Identifier
8527084
Citation
Cohen CR, Duerr A, Pruithithada N, Rugpao S, Hillier S, Garcia P, Nelson K. Bacterial vaginosis and HIV seroprevalence among female commercial sex workers in Chiang Mai, Thailand. AIDS. 1995 Sep;9(9):1093-7. doi: 10.1097/00002030-199509000-00017.
Results Reference
result
PubMed Identifier
26222747
Citation
Mitchell C, Fredricks D, Agnew K, Hitti J. Hydrogen Peroxide-Producing Lactobacilli Are Associated With Lower Levels of Vaginal Interleukin-1beta, Independent of Bacterial Vaginosis. Sex Transm Dis. 2015 Jul;42(7):358-63. doi: 10.1097/OLQ.0000000000000298.
Results Reference
result
PubMed Identifier
21992977
Citation
Ngugi BM, Hemmerling A, Bukusi EA, Kikuvi G, Gikunju J, Shiboski S, Fredricks DN, Cohen CR. Effects of bacterial vaginosis-associated bacteria and sexual intercourse on vaginal colonization with the probiotic Lactobacillus crispatus CTV-05. Sex Transm Dis. 2011 Nov;38(11):1020-7. doi: 10.1097/OLQ.0b013e3182267ac4.
Results Reference
result

Learn more about this trial

Phase 2 Trial of LACTIN-V in Women at High Risk of HIV Acquisition

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