BIYELA - Bexsero Immunisation in Young Women in Africa

Gonorrhea Clinical Trial

Official title: A Phase 3 Randomized, Observer-Blind, Placebo-Controlled Study to Assess Efficacy of Meningococcal Group B (rMenB+OMV NZ (Bexsero)) in Preventing Gonococcal Infection Among South African Cis-Gender Women

Status Not yet recruiting

Clinical Trial Summary

This proposed 2-arm randomized evaluation of two doses of 4CMenB vaccine versus placebo at Enrollment and Month 2 is designed as a proof-of-concept study to inform potential use for dual meningococcal B and gonococcal prevention, and to inform Neisseria gonorrheae vaccine development.

Clinical Trial Description

The World Health Organization (WHO) estimates that the global incidence of gonorrhea in 2020 was 82 million (CI: 48-130 million) among 15 to 49-year-olds, reflecting global incidence rates of 19/1000 women and 23/1000 men in that age group. Most gonococcal infections occur in LMICs. High rates of curable sexually transmitted infections (STIs) have been observed in pre-exposure prophylaxis (PrEP) demonstration projects conducted in adolescent girls and young women (AGYW) from eastern and southern Africa, with prevalences of Chlamydia trachomatis (CT) infection ranging from 24-30%, Neisseria gonorrheae (NG) infection from 7-10%, and syphilis seropositivity from 1-5%.

The consequences of bacterial STIs on AGYW's sexual and reproductive health can be substantial with long-term clinical repercussions: pelvic inflammatory disease (PID), chronic pelvic pain, tubal infertility, pregnancy complications, fetal and neonatal death, and increased susceptibility to HIV. Effective STI prevention interventions are needed to protect individuals, to prevent secondary transmission to partners, and to reduce the risk of long-term reproductive health consequences, particularly for women and their infants. STI prevention interventions could be integrated into PrEP programs, given the high prevalence and incidence of STIs in PrEP populations and the feasibility of providing integrated services in PrEP programs.

N.gonorrhoeae has been identified as a priority pathogen for the development of new vaccines and therapeutics given the current limited therapeutic options in the context of high rates of antimicrobial resistance. A vaccine for NG could mitigate the growing threat of antimicrobial resistance in NG, reduce the high NG prevalence and incidence among African women, and reduce the risk of reproductive morbidity from undiagnosed and untreated NG infection. Women have an increased risk of HIV due to bacterial STIs, both through direct mechanisms such as increased susceptibility due to genital inflammation, and indirectly through infertility, which is associated with increased condom-less sex as part of efforts to become pregnant. There are few other preventative bacterial STI interventions for women on the short-term horizon; unfortunately doxycycline post-exposure prophylaxis for STI prevention (doxy-PEP) was not effective for prevention of CT or NG among 449 Kenyan cis-gender women ages 18 to 30 who were taking HIV PrEP. This lack of efficacy appears to be in part due to adherence; doxycycline was detected in only 29% of 200 hair samples collected at follow-up visits from 50 randomly selected women in the doxy-PEP arm.

Gonorrhea may be vaccine-preventable. Several meningococcal outer membrane vesicle (OMV) proteins have >90% sequence homology with gonococcal OMV proteins. The meningococcal 4CMenB (Bexsero) vaccine (rMenB+OMV NZ), that targets serogroup B N. meningitidis, is a licensed OMV vaccine that contains protein antigens commonly expressed on the surface of both N. meningitidis and N. gonorrhoeae. It induces bactericidal antibodies that mediate killing of the majority of epidemiologically relevant serogroup B N. meningitidis strains. Gonococcal proteins share a high level of identity with several antigens contained in the Bexsero rMenB+OMV NZ vaccine and vaccination with Bexsero induces antibodies in humans that recognize gonococcal proteins 22, 26, 27, 23, 24, 28. In addition to OMV, the vaccine includes three purified recombinant N. meningitidis serogroup B protein antigens (rMenB), two which are fused with accessory antigens: 1) neisserial heparin binding antigen (NHBA), fused with the accessory protein genome-derived neisserial antigen (GNA) 1030, 2) factor H-binding protein (fHbp), fused to GNA2091, and 3) neisserial adhesin A (NadA), presented as a single antigen. NHBA is present in virtually all N. gonorrhoeae strains and its nucleotide and amino acid sequences are highly conserved (96.9% sequence identity in N. gonorrhoeae strains, with 71.3% identity to the Bexsero antigens). Gonococcal fHbp is similar to meningococcal variant 3, which is included in the vaccine, but is not surface exposed and therefore is not expected to contribute to protection. Both GNA2091 and GNA1030 accessory antigens are highly conserved; although their potential contribution to protection is unknown, they could provide an added effect. NadA is absent in gonococcal strains. In a humanized mouse model, 4CMenB immunized mice had antibodies that showed functional activity against NG, clearance of NG was accelerated and bacterial load reduced, serum immunoglobin G (IgG) and IgG cross-reacted with NG OMV and there was a four-fold increase in serum bactericidal50 titres all suggestive of 4CMenB activity against NG28. ;

Related Conditions & MeSH terms

• Gonorrhea
• Gonorrhea of Pharynx

• NCT number: NCT06446752
• Study type: Interventional
• Source: University of Washington
• Contact: Meighan Krows
• Phone: 206-520-3833
• Email: meigs@uw.edu
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 2024
• Completion date: August 2026