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

NCT05022212 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: LV-0071R01HD098978
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Bacterial Vaginosis; HIV Infections

Keywords

Vaginal microbiome; bacterial Vaginosis; HIV infections

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Genital Tract Inflammation

  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. The 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), measured as the number and proportions of endocervical CD4+ HIV target cells (i.e., CD4+/CCR5+/HLA-DR+/CD38+ T cells) at Day 64. Decreased inflammation will be defined using a measure of \>1 log10 decrease in 3/8 markers between baseline and Day 64.

  over 64 days

• Number of Participants With Lactobacillus-dominant Vaginal Microbiota

  The proportion of participants with Lactobacillus-dominant vaginal microbiota in young South African women. Measured will be dominance of Lactobacillus crispatus (defined as \> 50% relative abundance) after the intervention. Our primary outcome is measured at Day 36 (after 4 weeks of treatment with LACTIN-V), and at Day 64 (following the post- dosing phase).

  over 64 days

• Number of Participants With Vaginal Colonization of L. Crispatus CTV-05

  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. This primary outcome is measured at Day 36 (after 4 weeks of treatment with LACTIN-V), and at Day 64 (following the post- dosing phase).

  over 64 days

• Number of Participants With Vaginal Dysbiosis Indicated by a Nugent Score 4-10 on Vaginal Gram Stain

  The proportion of participants with a positive test for vaginal dysbiosis (Nugent Score 4-10 on vaginal Gram Stain) in each study arm by Day 36 and Day 64. The Nugent Score has values from 0 -10. 0-3 describes an optimal vaginal microbiome with lactobacilli but little bacterial diversity, 4-6 is an intermediate score, and 7-10 characterizes a vaginal microbiome with few lactobacilli and an overgrowth of pathogens.

  over 64 days

• Number of Participants Reporting Any Solicited Adverse Events (AEs) Through the Final Visit

  Overall Safety of LACTIN-V and the applicator will be measured by the proportion of participants reporting any solicited Adverse Events (AEs) through the final visit on Day 64, compared between study arms.

  over 64 days

• Number of Participants Willing to Use This Type of Product in the Future

  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. (Question "I would use the product again", on Day 36)

  over 36 days

Study Arms (2)

LACTIN-V

ACTIVE COMPARATOR

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.

Drug: LACTIN-V

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

LACTIN-V DRUG

administered vaginally

Also known as: Lactobacillus crispatus CTV-05

LACTIN-V

Placebo DRUG

administered vaginally

Placebo

Eligibility Criteria

• Age: 18 Years - 23 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• University of KwaZulu: collaborator
• Harvard University: collaborator
• Aurum Institute: collaborator
• Health Systems Trust: collaborator
• Osel, Inc.: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

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

Durban, KwaZulu-Natal, 4066, South Africa

Location

Related Publications (10)

• 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.

  PMID: 28087240 BACKGROUND

• 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.

  PMID: 22693410 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 19543144 BACKGROUND

• 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.

  PMID: 20644497 BACKGROUND

• 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.

  PMID: 8527084 BACKGROUND

• 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.

  PMID: 26222747 BACKGROUND

• 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.

  PMID: 21992977 BACKGROUND

• Hemmerling A, Govender V, Dong K, Dong M, Pillay S, Ndung'u T, Bhoola A, Moodley J, Casillas G, Lagenaur L, Mitchell CM, Kwon DS, Cohen CR. Acceptability of the live biotherapeutic LACTIN-V (Lactobacillus crispatus CTV-05) among young women at high risk of HIV acquisition in South Africa: data from the phase 2 placebo-controlled trial. Front Reprod Health. 2025 Mar 25;7:1544458. doi: 10.3389/frph.2025.1544458. eCollection 2025.

  PMID: 40206350 DERIVED

• Hemmerling A, Mitchell CM, Demby S, Ghebremichael M, Elsherbini J, Xu J, Xulu N, Shih J, Dong K, Govender V, Pillay V, Ismail N, Casillas G, Moodley J, Bergerat A, Brunner T, Liebenberg L, Ngcapu S, Mbano I, Lagenaur L, Parks TP, Ndung'u T, Kwon DS, Cohen CR. Effect of the vaginal live biotherapeutic LACTIN-V (Lactobacillus crispatus CTV-05) on vaginal microbiota and genital tract inflammation among women at high risk of HIV acquisition in South Africa: a phase 2, randomised, placebo-controlled trial. Lancet Microbe. 2025 Jun;6(6):101037. doi: 10.1016/j.lanmic.2024.101037. Epub 2025 Apr 4.

  PMID: 40194532 DERIVED

MeSH Terms

Conditions

Vaginosis, Bacterial; HIV Infections

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vaginitis; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Limitations and Caveats

In consideration of a set of circumstances that complicated the study progress (a 1-year delay of study start because of COVID-19 in 2020, a further 4-month delay because of destruction of the clinic site during social unrest in July 2021, and expiration of study product in March 2023), the study team together with the DSMB and the sponsor NICHD decided to stop enrollment at the end of 2022 at n=45, instead of the initial goal of n=60.

Results Point of Contact

• Title: Dr Anke Hemmerling, Co-Investigator
• Organization: University of California, San Francisco

anke.hemmerling@ucsf.edu

4154765878

Study Officials

• Craig R Cohen, MD MPH

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: May 7, 2021
• First Posted: August 26, 2021
• Study Start: May 10, 2021
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: August 13, 2024
• Results First Posted: August 13, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)