Phase 2b UK trial to test Lactin-V for preterm birth prevention

A phase 2b randomized trial in the United Kingdom is set to test whether the vaginal live biotherapeutic Lactin-V can reduce preterm birth risk in pregnant patients considered at high risk for early delivery, according to a company announcement from Osel Inc and March of Dimes. The study, FLIP-2, will compare Lactin-V to matching placebo in 360 participants across 4 UK maternity units.¹

The trial addresses a notable therapeutic gap. “For families facing the fear of preterm birth, the absence of effective treatments for microbiome imbalance in the reproductive tract is devastating,” Lynne Sykes, MD, chief investigator and clinical associate professor in obstetrics at Imperial College London, said in the announcement.¹ The launch comes as clinicians continue to navigate preterm birth prevention after the US Food and Drug Administration withdrew approval of hydroxyprogesterone caproate in 2023 because confirmatory data did not verify clinical benefit.²

According to the trial registration and company statement, FLIP-2 is a double-blind, placebo-controlled phase 2b study sponsored by Imperial College London.^1,3 It is evaluating Lactin-V, a vaginally administered powder containing Lactobacillus crispatus CTV-05, in pregnant women at elevated risk of preterm birth. The rationale is based on observational and translational work linking depletion of L crispatus and higher vaginal microbial diversity with genital tract inflammation and adverse obstetric outcomes, although whether modifying the microbiome will translate into fewer preterm births remains unproven.^1,4

The current study follows FLIP-1, an open-label pilot study published in 2023 that primarily assessed safety, tolerability, and acceptability in pregnant women at high risk of preterm birth.¹ In that report, investigators found Lactin-V was generally well tolerated and acceptable to participants; the press release also noted a lower preterm birth rate than in historical controls, but that comparison was not derived from a randomized design and should be interpreted cautiously.¹ The phase 2b study is intended to provide more rigorous evidence on efficacy and safety.

Preterm birth remains a leading cause of neonatal morbidity and mortality worldwide, especially at earlier gestational ages.⁴ Prevention strategies currently depend on underlying risk factors and may include cervical-length surveillance, cerclage in selected patients, and vaginal progesterone in some settings, although recommendations and evidence vary by phenotype of risk and by region.^2,4 In the United States, the regulatory withdrawal of Makena narrowed already limited pharmacologic options specifically approved for recurrent preterm birth prevention.²

Lactin-V belongs to the emerging category of live biotherapeutic products, defined by the US Food and Drug Administration (FDA) as biological products containing live organisms intended for prevention, treatment, or cure of disease.⁵ Outside pregnancy, the product has previously been studied for prevention of recurrent bacterial vaginosis after antibiotic treatment. In a phase 2b trial published in 2020, women receiving Lactin-V had a lower incidence of bacterial vaginosis recurrence by week 12 than those receiving placebo, supporting proof of concept for vaginal colonization and microbiome-directed therapy.⁶ That indication, however, differs substantially from prevention of spontaneous preterm birth in pregnancy.

The biologic premise is clinically interesting because preterm birth is heterogeneous, and inflammation-associated pathways may be particularly relevant for a subset of patients. Still, enthusiasm should be tempered by the history of interventions that showed biologic plausibility but did not improve birth outcomes in larger trials. The company announcement did not provide prespecified primary or secondary end points, gestational age thresholds for enrollment, or details on subgroup definitions beyond “high risk,” all of which will be important for interpreting any eventual results.^1,3

Safety will be central. Although FLIP-1 suggested acceptable short-term tolerability in pregnancy, any microbiome-based intervention used antenatally will need careful assessment for maternal infection-related events, obstetric complications, and neonatal outcomes before clinical adoption.¹ Because FLIP-2 is a mid-stage trial, positive results would still require confirmation before any regulatory application.

References

1. Osel Inc. and March of Dimes announce groundbreaking phase 2b trial of microbiome-based therapy targeting preterm birth prevention. News release. Osel. May 13, 2026. Accessed May 13, 2026. https://www.businesswire.com/news/home/20260513341126/en/Osel-Inc.-and-March-of-Dimes-Announce-Groundbreaking-Phase-2b-Trial-of-Microbiome-based-Therapy-Targeting-Preterm-Birth-Prevention

2. FDA commissioner and chief scientist announce decision to withdraw approval of Makena. FDA. News release. April 6, 2023. Accessed May 13, 2026. https://www.fda.gov/news-events/press-announcements/fda-commissioner-and-chief-scientist-announce-decision-withdraw-approval-makena

3. A study to test if Lactin-V, a type of probiotic made from a specific bacteria (Lactobacillus crispatus CTV-05), is safe and effective in lowering the chances of preterm labour in women who are considered at high risk for giving birth early. ISRCTN Registry. Updated April 15, 2026. Accessed May 13, 2026. https://www.isrctn.com/ISRCTN13610566

4. Preterm birth. World Health Organization. Updated May 10, 2023. Accessed May 13, 2026. https://www.who.int/news-room/fact-sheets/detail/preterm-birth

5. Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing, and Control Information: Guidance for Industry. US Food and Drug Administration; 2016. Accessed May 13, 2026. https://www.fda.gov/files/vaccines,%20blood%20%26%20biologics/published/Early-Clinical-Trials-With-Live-Biotherapeutic-Products--Chemistry--Manufacturing--and-Control-Information--Guidance-for-Industry.pdf

6. Cohen CR, Wierzbicki MR, French AL, et al. Randomized trial of Lactin-V to prevent recurrence of bacterial vaginosis. N Engl J Med. 2020;382(20):1906-1915. doi:10.1056/NEJMoa1915254