Early safety and efficacy results on a contraceptive vaginal film that inactivates sperm

By Dr. Liji Thomas, MDReviewed by Benedette Cuffari, M.Sc.Mar 7 2023

Contraceptives with greater accessibility and acceptance are urgently needed in countries with high unplanned pregnancy rates.

As a response to the growing demand for contraceptives, the monoclonal antibody company ZabBio developed ZB-06, a vaginal film with HC4-N, a human contraceptive antibody (HCA) that inactivates sperm. A new research paper reports the earliest safety results from the trial for a vaginal film incorporating an anti-sperm HCA.

Study: ZB-06, a vaginal film containing an engineered human contraceptive antibody (HC4-N), demonstrates safety and efficacy in a phase 1 postcoital test and safety study. Image Credit: ADragan / Shutterstock.com

Introduction

Throughout the world, family planning has become increasingly important, with up to 842 million people currently using contraceptive methods. Nevertheless, the World Health Organization estimates that up to 270 million people worldwide still need access to effective contraceptives.

Several different contraceptive methods are currently available worldwide, including oral contraceptive pills, implants, injectables, patches, vaginal rings, intrauterine devices, and condoms.  

Each of these methods is associated with different advantages and disadvantages. The use of hormonal contraceptives, in particular, may lead to adverse effects, such as menstrual cycle changes and delays in future fertility capabilities.

Thus, there remains an urgent need for a non-hormonal contraceptive that does not involve detergents, which have been shown to be harmful to the vaginal microflora. The ideal contraceptive would also be available on demand.

Currently, the only non-hormonal, on-demand and female-controlled contraceptive includes barrier methods such as female condoms and diaphragms, both of which have relatively low uptake worldwide. Nonoxynol-9 (N-9) and other spermicides are also non-hormonal contraceptives; however, their frequent use may cause vaginal dysbiosis, which may increase the risk of being infected with the human immunodeficiency virus (HIV).

As a result, N9-based spermicides are not recommended in areas where this virus is prevalent, despite the fact that these areas often have an increased demand for contraceptives.

HCAs are human monoclonal antibodies with the H6-3C4 sequence and are associated with potent sperm agglutination and immobilization. These antibodies, which were first identified in the blood of an infertile female, target CD52g, which is a glycoprotein that is present on sperm, as well as various other locations throughout the male reproductive tract.

About the study

The current study, which is published in the American Journal of Obstetrics and Gynecology, aimed to explore the contraceptive potential of the HCA-containing vaginal film called ZB-06. ZB-06 contains the immunoglobulin G1 (IgG1) HCA HC4-N, which was produced by an engineered strain of the tobacco plant.

Eight healthy women who were between 18 and 50 years of age, did not use any hormonal contraceptives, and experienced regular menstrual cycles participated in the current study. All women were previously surgically sterilized and were currently sexually active with a male partner with no history of sterility or infertility.

Once the study participants confirmed that they were ovulating, they were asked to visit the clinic for a vagina or cervical mucus check (CMC) visit. Herein, the researchers confirmed that no sperm was present in the vagina or cervical mucus prior to timed and unprotected intercourse.

Within two to three hours after intercourse, the study participant again presented to the clinic for a postcoital test (PCT) to identify the number of active motile normal sperms in the vaginal fluid following intercourse. The researchers also assessed samples for the presence of anti-sperm antibodies, sperm agglutination potential, inflammatory cytokines, and the Nugent score for vaginal dysbiosis after the use of the film.

What did the study show?

The use of the vaginal film was found to be clinically safe over the short term for both partners. The baseline PCT on ovulatory CM showed an average of about 26 progressively motile sperms (PMS) in a single high-power field (HPF). Post-film, however, when used before intercourse, PMS levels were only 0.04 PMS/HPF.

With product use, all eight female participants had less than 5 PMS/hpf in ovulatory cervical mucus, the current surrogate contraceptive efficacy benchmark for the PCT test.”

The effect due to the mucosal anti-sperm antibodies persisted for three or more hours from the point of use.

Cytokine levels did not differ after intercourse with or without the film. Anti-sperm antibodies could not be detected in CM or vaginal fluid samples, or in most participants, due to the insensitivity of the custom assay employed in the study.

One participant exhibited the presence of the antibody HC4-N throughout the course of the study, irrespective of product use. This might have been a non-specific reaction, as her serum did not cause sperm agglutination, which was observed in the serum samples from all other participants.

At a follow-up visit about one month later, PCT at this time without the use of the film was about 47 PMS/HPF. Thus, the effect of the film appears to be reversible.

What are the implications?

The scientists concluded that just one dose of the film was safe and could prevent fertilization of the ovum by PMS in ovulatory CM. These findings demonstrate the efficacy of ZB-06 as a viable contraceptive candidate and support further development and testing. Importantly, intensive safety evaluations are still needed, as the current findings were based on a single-exposure study.

While these preliminary findings may be reassuring, the current study was associated with certain limitations, including a very small sample size that only consisted of non-potential users of the product, and only a single timed exposure was assessed.