Gonococcal Vaccine Study in Key Populations in Kenya (BexKPK)

Use of Bexsero Immunisation to Detect Cross Reactive Antigens and Anti-gonococcal Antibodies in Key Populations in Kenya

Gonorrhoea is a sexually transmitted infection that can infect both men and women. It can cause infections in the genitals, rectum, and throat. It is a very common infection, especially among young people aged 18-25 years.

Meningococcal disease and gonorrhoea are caused by bacteria that are closely related but cause different diseases that are spread in different ways. New evidence suggests that the Meningococcal B vaccine (Bexsero®) licensed outside of Kenya against meningococcal B disease may also be effective against gonorrhoea due to genetic similarities between the two organisms causing the two diseases. The aim of this study is to generate data to develop a gonorrhoea vaccine, using an existing vaccine against meningococcal disease

Study Overview

• Status: Completed
• Conditions: Gonorrhea
• Intervention / Treatment: Biological: 4CMenB (Bexsero®) vaccine

Detailed Description

Meningococcal disease and gonorrhoea are caused by bacteria that are closely related but cause different diseases that are spread in different ways. New evidence suggests that the Meningococcal B vaccine (Bexsero®) licensed outside of Kenya against meningococcal B disease may also be effective against gonorrhoea due to genetic similarities between the two organisms causing the two diseases. Investigators will conduct a clinical trial of the Meningococcal B vaccine (Bexsero®) in approximately 50 male and female participants aged 18-25 years who are in follow up in KEMRI cohorts (including HIV-uninfected and infected individuals) at the KEMRI clinic in Mtwapa. This is not an efficacy trial. Instead, investigators will assess if immunisation of individuals at risk for gonococcal infection with 4CMenB (Bexsero®) elicits humoral and T cell cross-reactive responses against Neisseria gonorrhoeae (Ng). Participants will make six study visits, including a screening visit, an enrolment visit and 4 follow up visits. InvestigatorsF will offer vaccination with the Meningococcal B vaccine (Bexsero®) vaccine at the enrolment visit and approximately 2 months later. Investigators will collect a 20ml blood sample at enrolment, and following the first vaccination, and a 70ml blood sample following the second vaccination. At study completion (month 6), investigators will collect a 4ml blood sample. Investigators will collect a throat swab, a urine sample (for men), vaginal swab, and an anal swab at the enrolment, month 3 and month 6 visit to test for Chlamydiae and Gonorrhoea infection. Total study participation for participants is 6 months. Upon study completion, participants will continue to receive research care at the KEMRI clinic in Mtwapa.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Kenya
  • Kilifi, Kenya
    • KEMRI-Wellcome Trust Research Programme

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 25 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female as assessed by a medical history, physical exam, and laboratory tests (specified in study operations manual).
• At least 18 years of age on the day of screening and will not reach 26th birthday on the day of the second vaccination (approximately 6 weeks after enrolment)
• Willing and able to give informed consent for participation in the trial before any study-related procedures are performed.
• Willing to donate blood samples for immunogenicity assessments.

Exclusion Criteria:

Any clinically significant acute or chronic medical condition that is considered progressive that, in the opinion of the Principal Investigator or designee, makes the volunteer unsuitable for participation in the trial

• Pregnancy
• Participation in another clinical trial (i.e. investigational HIV vaccine candidate), within the previous 3 months or expected participation during the study
• Bleeding disorder diagnosed by a physician (e.g., factor deficiency, coagulopathy or platelet disorder that requires special precautions).
• History of severe local or systemic reactogenicity to vaccines (e.g., anaphylaxis, respiratory difficulty, angioedema).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Bexsero; Each participant is compared to baseline (before vaccination)	Biological: 4CMenB (Bexsero®) vaccine; Tthe 4CMenB vaccine (Bexsero®) contains the MeNZB OMV component plus three recombinant antigens (NadA, fHBP-GNA2091, and NHBA-GNA1030. The 4CMenB vaccine (Bexsero®) induces antibodies in humans that recognise gonococcal proteins.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
humoral and T cell cross-reactive responses against Neisseria gonorrhoeae	Serum antigen- and OMV-specific IgG1, IgG2a, Ig3A and IgA titres will be determined. T cell responses will be measured in two ways: Indirect responses: by determining the IgG1/IgG2 ratios after immunization. Direct responses: PBMCs will be isolated at enrolment, 2 weeks post second immunization and used for the detection of antigen-specific IFN secreting T cells. The induction of antibody will be measured by a standard endpoint ELISA assay using peptides covering recombinant protein antigens, purified antigens, and defined OMVs. After the final immunization, PBMCs will be collected for isolation of antigen-specific memory B cells, aiming to generate human monoclonal antibodies (mAbs) against key vaccine candidates.	approximately 2 weeks following completed vaccination (2 doses)

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: KEMRI-Wellcome Trust Collaborative Research Program
• Investigators: Principal Investigator: Eduard Sanders, MD, PhD, University of Oxford & KEMRI-Wellcome Trust

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2021
• Primary Completion (Actual): February 5, 2022
• Study Completion (Actual): February 28, 2022

Study Registration Dates

• First Submitted: February 27, 2020
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (Actual): March 5, 2020

Study Record Updates

• Last Update Posted (Actual): April 14, 2022
• Last Update Submitted That Met QC Criteria: April 13, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Communicable Diseases; Sexually Transmitted Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Sexually Transmitted Diseases, Bacterial; Gonorrhea
• Other Study ID Numbers: CSC 182; OXTREC16-20 (Other Identifier: University of Oxford)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

All trial data will be entered in the clinical trial database, which are maintained through Standard Operating Procedures.

The volunteer will be identified by a unique trial specific number and/or code in any database. The name and any other identifying detail will NOT be included in any trial data electronic file.

• IPD Sharing Time Frame: during study and storage for 10 years
• IPD Sharing Access Criteria: Direct access will be granted to authorised representatives from the Sponsor, host institution and the regulatory authorities to permit trial-related monitoring, audits and inspections.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No