Ignite Creation Date:
2024-06-16 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06446752
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-06
First Post:
2024-05-11
Brief Title:
BIYELA - Bexsero Immunisation in Young Women in Africa
Sponsor:
University of Washington
Organization:
University of Washington
Study Overview
Official Title:
A Phase 3 Randomized Observer-Blind Placebo-Controlled Study to Assess Efficacy of Meningococcal Group B rMenBOMV NZ Bexsero in Preventing Gonococcal Infection Among South African Cis-Gender Women
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
Detailed 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 191000 women and 231000 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 AGYWs 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
Ngonorrhoeae 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 rMenBOMV 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 rMenBOMV 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 969 sequence identity in N gonorrhoeae strains with 713 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
The consequences of bacterial STIs on AGYWs 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
Ngonorrhoeae 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 rMenBOMV 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 rMenBOMV 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 969 sequence identity in N gonorrhoeae strains with 713 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None