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

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.

Start Date10 May 2021

Sponsor / Collaborator

The University of California, San Francisco

[+5]

NCT03992534

/ Unknown statusPhase 1IIT

Feasibility, Safety, Tolerance and Assessment of LACTIN-V Use in a Cohort of Pregnant Women at Risk of Preterm Birth

Preterm birth (PTB) is the primary cause of infant death worldwide. It has been shown that a vaginal microbiota deplete in Lactobacillus species is a risk factor for preterm labour. Conversely a vaginal microbiota dominated by Lactobacillus crispatus appears to be protective for these adverse outcomes. A wide range of 'over the counter' Lactobacillus spp. containing products targeted at 'vaginal health' and formulated for vaginal administration are available, but most of them do not contain vaginal species of Lactobacillus. The primary aim of this study is to determine whether vaginal supplementation with L. crispatus CTV-05 is associated with colonisation.

Start Date16 Sep 2019

Sponsor / Collaborator

Imperial College London

[+1]

NCT02766023

/ CompletedPhase 2IIT

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.

Start Date03 Jun 2016

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

100 Clinical Results associated with CTV-05

100 Translational Medicine associated with CTV-05

100 Patents (Medical) associated with CTV-05

Literatures (Medical) associated with CTV-05

01 Apr 2025·Lancet Microbe

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

Article

Author: Dong, Krista ; Mbano, Ian ; Demby, Suuba ; Ndung'u, Thumbi ; Brunner, Tess ; Kwon, Douglas S ; Parks, Thomas P ; Xulu, Nondumiso ; Lagenaur, Laurel ; Moodley, Jayajothi ; Cohen, Craig R ; Bergerat, Agnes ; Elsherbini, Joseph ; Shih, Johnathan ; Ngcapu, Sinaye ; Ismail, Nasreen ; Gebremichael, Musie ; Govender, Vaneshree ; Mitchell, Caroline M ; Liebenberg, Lenine ; Xu, Jiawu ; Hemmerling, Anke ; Casillas, Gardenia ; Pillay, Vanessa

BACKGROUND:

Absence of vaginal lactobacilli and accompanying genital inflammation is associated with HIV acquisition. We aimed to assess how a vaginal live biotherapeutic containing Lactobacillus crispatus affects cervicovaginal microbiota and markers of HIV susceptibility in South African women.

METHODS:

This randomised, placebo-controlled, phase 2 trial evaluated LACTIN-V (L crispatus CTV-05), a vaginal live biotherapeutic, compared with placebo in cisgender women in South Africa, aged 18-23 years, recruited at a community-based research clinic. Eligible participants with a Nugent score of 4-10 (indicating intermediate vaginal microbiota or bacterial vaginosis) completed 7 days of oral metronidazole and were randomly assigned (2:1) to LACTIN-V (2 × 10⁹ colony forming units per dose) or placebo (the substrate alone) via an independently generated randomisation sequence. Pharmacists, participants, and investigators were masked to treatment assignment. The study product (or placebo) was dosed daily for 5 days in week 1, then twice per week for an additional 3 weeks. Adverse events were evaluated 4 weeks and 8 weeks after starting the study product. Vaginal swabs (for 16S rRNA sequencing of the vaginal microbiome) and cervicovaginal lavage (for Luminex analysis of immune markers) were collected before metronidazole treatment, before study product (or placebo) administration, and at the week 4 and week 8 follow-up visits. An endocervical cytobrush for flow cytometry analysis of immune cell populations (including CD3⁺CD4⁺ T cells, and presence of CCR5 and the activation markers CD38 or HLA-DR) was collected before study product use and at 4 weeks and 8 weeks after study product use. The coprimary outcomes for the trial were (1) safety and acceptability of LACTIN-V, as measured by number of adverse events and a validated questionnaire; (2) presence of a Lactobacillus-dominant vaginal microbial community by 16S rRNA gene sequencing at week 4 and week 8; and (3) comparison of change in genital tract inflammatory markers from before metronidazole treatment to week 4 and week 8 between groups. Safety analyses were done in the intention-to-treat population and efficacy analyses in a modified intent-to-treat population (ie, excluding one person assigned placebo who erroneously received LACTIN-V). This trial is completed and registered on ClinicalTrials.gov (NCT05022212).

FINDINGS:

45 Black South African women were randomly assigned to receive LACTIN-V (n=32) or placebo (n=13). One woman in each group discontinued the trial during the intervention and two women discontinued during the follow-up. No severe or serious adverse events were observed. Solicited adverse events occurred in 35 (78%) of 45 participants with no significant difference by group (risk ratio 1·17, 95% CI 0·79-1·75; p=0·44). All local solicited adverse events were mild. 32 (71%) of 45 participants strongly agreed or agreed they would use the product again. L crispatus dominant microbiomes were identified in 13 (41%) of 32 participants in the LACTIN-V group at week 4 and eight (26%) of 31 at week 8, compared with none at week 4 and one (9%) of 11 in week 8 in the placebo group (week 4 p=0·0088; week 8 p=0·40). The proportion of activated endocervical HIV target cells out of total T cells increased from after metronidazole treatment to week 4 in the placebo group (median log₂ fold change 1·891, IQR 1·731-4·018) but not in the LACTIN-V group (1·062, 0·449-1·424; p=0·016). Changes in the concentrations of 13 immune markers from before metronidazole treatment to week 4 or week 8 were not significantly different by group.

INTERPRETATION:

The use of LACTIN-V after metronidazole significantly increased vaginal L crispatus colonisation during 4 weeks of use, although this increase was transient, and women in the placebo group had an increase in endocervical CD4⁺ HIV target cells during recovery compared with the LACTIN-V group. These results show that vaginal colonisation with an L crispatus live biotherapeutic is possible in an African context, and that optimisation of this strategy might be a way to decrease risk for HIV.

FUNDING:

US National Institute of Child Health and Human Development and US National Institute of Allergy and Infectious Diseases.

06 Aug 2024·Microbiology Spectrum

Vaginal fungi are associated with treatment-induced shifts in the vaginal microbiota and with a distinct genital immune profile

Article

Author: Crawford, Emily ; Liu, Rachel ; Armstrong, Eric ; Huibner, Sanja ; Cohen, Craig R ; Kulikova, Maria ; Coburn, Bryan ; Castañeda, Gloria R ; Hemmerling, Anke ; Kaul, Rupert ; Miller, Steve

ABSTRACT:

Vaginal colonization by fungi may elicit genital inflammation and enhance the risk of adverse reproductive health outcomes, such as HIV acquisition. Cross-sectional studies have linked fungi with an absence of bacterial vaginosis (BV), but it is unclear whether shifts in vaginal bacteria alter the abundance of vaginal fungi. Vaginal swabs collected following topical metronidazole treatment for BV during the phase 2b, placebo-controlled trial of LACTIN-V, a Lactobacillus crispatus -based live biotherapeutic, were assayed with semi-quantitative PCR for the relative quantitation of fungi and key bacterial species and multiplex immunoassay for immune factors. Vaginal fungi increased immediately following metronidazole treatment for BV (adjusted P = 0.0006), with most of this increase attributable to Candida albicans . Vaginal fungi were independently linked to elevated levels of the proinflammatory cytokine interleukin (IL) 17A, although this association did not remain significant after correcting for multiple comparisons. Fungal relative abundance by semi-quantitative PCR returned to baseline levels within 1 month of metronidazole treatment and was not affected by LACTIN-V or placebo administration. Fungal abundance was positively associated with Lactobacillus species, negatively associated with BV-associated bacteria, and positively associated with a variety of proinflammatory cytokines and chemokines, including IL-17A, during and after study product administration. Antibiotic treatment for BV resulted in a transient expanded abundance of vaginal fungi in a subset of women which was unaffected by subsequent administration of LACTIN-V. Vaginal fungi were positively associated with Lactobacillus species and IL-17A and negatively associated with BV-associated bacteria; these associations were most pronounced in the longer-term outcomes.

IMPORTANCE:

Vaginal colonization by fungi can enhance the risk of adverse reproductive health outcomes and HIV acquisition, potentially by eliciting genital mucosal inflammation. We show that standard antibiotic treatment for bacterial vaginosis (BV) results in a transient increase in the absolute abundance of vaginal fungi, most of which was identified as Candida albicans . Vaginal fungi were positively associated with proinflammatory immune factors and negatively associated with BV-associated bacteria. These findings improve our understanding of how shifts in the bacterial composition of the vaginal microbiota may enhance proliferation by proinflammatory vaginal fungi, which may have important implications for risk of adverse reproductive health outcomes among women.

01 Jun 2024·SEXUALLY TRANSMITTED DISEASES

Response to Antibiotic Treatment of Bacterial Vaginosis Predicts the Effectiveness of LACTIN-V (Lactobacillus crispatus CTV-05) in the Prevention of Recurrent Disease

Article

Author: Armstrong, Eric ; Hemmerling, Anke ; Wierzbicki, Michael R. ; Cohen, Craig R.

Objectives:

Live biotherapeutic products (LBPs) containing vaginal Lactobacillus crispatus are promising adjuvant treatments to prevent recurrent bacterial vaginosis (BV) but may depend on the success of initial antibiotic treatment.

Methods:

A post hoc analysis of data collected during the phase 2b LACTIN-V randomized control trial (L. crispatus CTV-05) explored the impact of clinical BV cure defined as Amsel criteria 0 of 3 (excluding pH, per 2019 Food and Drug Administration guidance) 2 days after completion of treatment with vaginal metronidazole gel on the effectiveness of an 11-week LACTIN-V dosing regimen to prevent BV recurrence by 12 and 24 weeks.

Results:

At enrollment, 88% of participants had achieved postantibiotic clinical BV cure. The effect of LACTIN-V on BV recurrence compared with placebo differed by initial clinical BV cure status. The LACTIN-V to placebo risk ratio of BV recurrence by 12 weeks was 0.56 (95% confidence interval, 0.35–0.77) among participants with initial clinical BV cure after metronidazole treatment and 1.34 (95% confidence interval, 0.47–2.23) among participants without postantibiotic clinical BV cure. Among women receiving LACTIN-V, those who had achieved postantibiotic clinical BV cure at enrollment reached higher levels of detectable L. crispatus CTV-05 compared with women failing to achieve postantibiotic clinical BV cure.

Conclusions:

LACTIN-V seems to only decrease BV recurrence in women with clinical cure of BV after initial antibiotic treatment. Future trials of LBPs should consider limiting enrollment to these women.

News (Medical) associated with CTV-05

03 Feb 2021

·www.biospace.com

Osel Obtains Exclusive License from Danish Research Consortia for IP Related to Osel’s LACTIN-V in Women Undergoing In-Vitro Fertilization

MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)-- Osel, Inc., a company developing live biotherapeutic products (LBPs) for diseases linked to the disruption of the human microbiome, today announced that it has entered into a definitive agreement with a consortia comprising Aarhus University, Skive Hospital and Statens Serum Institut of Denmark, and obtained the exclusive worldwide license to inventions resulting from an investigator-initiated Phase 2 trial of Osel’s investigational LBP, LACTIN-V, in women undergoing in-vitro fertilization (IVF). Financial terms were not disclosed. Osel is developing LACTIN-V, a proprietary formulation of Lactobacillus crispatus being studied in IVF, in addition to bacterial vaginosis (BV) and pre-term birth. Last year, Osel and colleagues published data in The New England Journal of Medicine demonstrating that LACTIN-V significantly reduced the recurrence of BV versus placebo in a Phase 2b trial. “Dysbiosis, or disruption of the vaginal microbiome, can lead to many problems in women’s health including BV and decreasing the success rate of IVF,” said Peter P. Lee, MD, Founder and Executive Chairman of Osel. “LACTIN-V, which contains the protective vaginal bacterial strain L. crispatus CTV-05, could help promote a healthier vaginal microbiome for IVF.” Under the agreement, the ongoing Phase 2 IVF trial is being conducted at four fertility clinics in Denmark and led by Professor Peter Humaidan, MD, Aarhus University and Skive Regional Hospital. The primary endpoint of the trial is clinical pregnancy at seven weeks post-embryo transfer in women with documented abnormal vaginal microbiota, which lowers the probability of successful IVF. “The vaginal microbiome and its importance for fertility is an intriguing new field of research. In the near future we hope to be able to define the most optimal vaginal microbiome – and importantly, to be able to modify the abnormal to normal,” said Professor Humaidan. “The ultimate goal of our research is to improve success rates of not only IVF, but also spontaneous pregnancy.” “LACTIN-V holds promise as the first treatment to increase the possibility of pregnancy from IVF, especially in women with vaginal dysbiosis,” said Thomas Parks, PhD, Director of Product Development at Osel. “While the trial’s progress was impacted by COVID-19, we expect to complete enrollment by the end of 2021/early 2022.” About Osel, Inc. Osel, Inc., a privately held biopharmaceutical company based in Mountain View, California, is focused on the development and commercialization of a portfolio of live biotherapeutic products (LBPs) to prevent or treat medical conditions resulting from disruption of the human microbiome (dysbiosis). The company is a pioneer in the field of LBPs, with a primary focus in women’s health. While many current microbiome treatments involve microbial transplants that are collected and processed from donor pools, Osel focuses on rigorously selected single strain products that are highly reproducible, scalable, and safe. Visit oselinc.com to learn more.

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100 Deals associated with CTV-05

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Bacterial Vaginosis	Phase 3	United States	Osel, Inc.	22 Jul 2022
Urinary Tract Infections	Phase 3	United States	University of Washington	01 Sep 2015
HIV Infections	Phase 2	South Africa	Osel, Inc.	10 May 2021
Female genital tract infection	Phase 2	United States	The Medicines Co.	17 Aug 2000
Obstetric Labor, Premature	Phase 1	United States	Osel, Inc.	22 Jul 2022
Candidiasis	Preclinical	United States	Osel, Inc.	31 Aug 2011

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05022212 (CTgov)	Phase 2	HIV Infections \| Bacterial Vaginosis	45	LACTIN-V (LACTIN-V)	dzdmhkbrtw = aqjwlckzhn epzxlpwjup (kxijbwfaxk, qfcxgcwhsz - qeyxmrghaf) View more	-	13 Aug 2024
				Placebo (Placebo)	dzdmhkbrtw = usqykpbpcy epzxlpwjup (kxijbwfaxk, wbhhwfulff - uvaosvyooe) View more
NCT03151967 (CTgov)	Phase 2/3	Urinary Tract Infections	27	Lactobacillus crispatus CTV-05 (Applicator With LACTIN-V Treatment)	ogvpofgypn = vykiaglwip azukybmeyd (gdtidywbuj, njaovpcadc - baqddmovrj) View more	-	01 Mar 2023
				Placebo (Applicator With Placebo)	ogvpofgypn = hxcwbtirul azukybmeyd (gdtidywbuj, zfdpwitetx - wnnetxoklc) View more
NCT02766023 (Pubmed) Manual	Phase 2	Bacterial Vaginosis	228	Lactin-V	hlybdiylpz(zgdzalnkjn) = witbyrwhhz fzcxfzbncw (naztdvkdsx ) View more	Positive	14 May 2020
				Placebo	hlybdiylpz(zgdzalnkjn) = cnyqpvjcla fzcxfzbncw (naztdvkdsx )
NCT02766023 (CTgov)	Phase 2	Bacterial Vaginosis	228	Metronidazole+Lactobacillus crispatus CTV-05 (LACTIN-V)	efgkkevfdy = qxedtauooi bnbjqkvyje (wahmosgnnm, nkxngylfju - wmaeoansun) View more	-	11 Feb 2020
				Placebo+Metronidazole (Placebo)	efgkkevfdy = xydekryxlg bnbjqkvyje (wahmosgnnm, hgzjthketb - dlcobcobsn) View more
NCT00305227 (CTgov)	Phase 2	Urinary Tract Infections	100	Lactin-V (Lactin-V)	vtzecbtqap = ccpcouolie ystuziqvno (gzzntxewbf, melejeurgs - fgfymwngck) View more	-	04 Jul 2014
				Placebo (Placebo)	vtzecbtqap = eoittrmudl ystuziqvno (gzzntxewbf, brrzblgvjc - zawyngpjvx) View more

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