BIYELA - Bexsero Immunisation in Young Women in Africa

NCT06446752 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: STUDY00019050
• Study Type: interventional
• Target: 1,100
• Locations: 1 country
• Sites: 5

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.

Conditions

Gonorrhea; Gonorrhea of Pharynx; Gonorrhea of Anus; Gonorrhea of Cervix

Keywords

sexually transmitted infections; STI; Gonorrhea

Outcome Measures

Primary Outcomes (1)

• First diagnosis of gonorrhea at cervical or anorectal sites occurring greater than or equal to 1 month after the second vaccination with study product through to the study end

  Assess efficacy of Bexsero in prevention of cervical and/or anorectal gonococcal infection

  18 months

Secondary Outcomes (4)

• First diagnosis of gonorrhea at cervical or anorectal sites occurring >1 month after the second vaccination with study product through to study end, by specified subgroups

  18 months

• First diagnosis of pharyngeal gonorrhea occurring > 1 month after the second vaccination with study product through to study end, by study arm

  18 months

• Cumlative GC incidence in the first 9 months after receipt of the second dose of vaccine compared to cumlative GC incidence in the 10-16 months after receipt of the second dose

  18 months

• To ascertain the safety of Bexsero

  18 months

Study Arms (2)

Bexsero

EXPERIMENTAL

Meningococcal Serogroup B vaccine rMenB+OMV NZ (Bexsero) administered as an IM injection by 0.5-mL single-dose syringe at enrollment (Visit 1) and 2 months post-enrollment (Visit 3).

Biological: Bexsero

Placebo

PLACEBO COMPARATOR

Normal saline (placebo) administered as an IM injection by 0.5-mL single-dose syringe at enrollment (Visit 1) and 2 months post-enrollment (Visit 3).

Biological: Placebo

Interventions

Bexsero BIOLOGICAL

Administered as an IM injection by 0.5-mL single-dose syringe at enrollment (Visit 1) and 2 months post-enrollment (Visit 3).

Also known as: 4MenB-4C

Bexsero

Placebo BIOLOGICAL

Administered as an IM injection by 0.5-mL single-dose syringe at enrollment (Visit 1) and 2 months post-enrollment (Visit 3).

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Individuals born female aged 18-45 years of age inclusive on the day of screening
• In good health as determined by past medical history, medication use, and targeted physical examination,
• If not living with HIV, negative HIV test conducted at screening
• If living with HIV, on an antiretroviral regimen for ≥3 months, with an undetectable HIV RNA of \<200 copies/ml and/or a CD4 count \>300 cells/cmm within 12 months of screening
• If of reproductive potential,
• Willing to not become pregnant during vaccination period and
• Have a negative pregnancy test prior to each vaccination and
• Willing to use a reliable method of contraception until month 3 (i.e., after the second vaccination visit)
• Not breastfeeding
• Sexually active in the past 3 months, defined as vaginal or anal sex
• At risk for gonorrhea based on sexual behaviour characteristics including
• Previous PrEP use in the past 12 months, or
• Past history of STIs in the past 12 months, or
• or more partners in the past 12 months
• Has provided signed informed consent, and is willing and likely to comply with the trial procedures and follow-up visit requirements

You may not qualify if:

• Contra-indications to Bexsero
• Previous receipt of a Meningococcal Group B vaccine
• Receipt of antibiotics active against N. gonorrhoeae in the 14 days prior to the Enrollment Visit, including oral or parenteral antibiotics\*
• Participants with NG and/or CT detected at screening may re-screen after receiving appropriate antibiotic treatment
• Planned long-term (\> 4 weeks) antibiotic use for prophylaxis or treatment for acne or other bacterial condition(s)
• Use or planned use of a live vaccine within +/- 30 days, an inactive vaccine within +/- 14 days, or an influenza vaccine within +/- 7 days from receipt of study product. Authorized or approved, inactivated COVID-19 vaccines may be given more than 7 days +/- receipt of study product for all study participants
• Use of any investigational drug or vaccine within 30 days prior to enrollment, or planned/anticipated use during study participation
• Currently receiving immunosuppressive agent or systemic corticosteroids (dose \>5 mg/day of prednisone) for \>14 consecutive days within 90 days prior to enrollment. Topical or inhaled steroids are allowed. Topical steroids cannot be applied to study product injection site
• Has received antineoplastic (chemotherapy) or radiotherapy within 90 days prior to enrollment
• Has received immunoglobulins and/or any blood products within 180 days prior to enrollment
• Progressive, unstable, or uncontrolled disease including but not limited to cardiac, hepatic, renal, immunological, neurological or psychiatric conditions
• Has a condition which in the opinion of the investigator is not suitable for intramuscular vaccination, blood draws, or participation in the trial
• Pregnant or breastfeeding at enrollment

Sponsors & Collaborators

• University of Washington: lead
• Bill and Melinda Gates Foundation: collaborator
• University of Witwatersrand, South Africa: collaborator

Study Sites (5)

Desmond Tutu Health Foundation - Emavundleni Research Centre

Cape Town, South Africa

Location

Desmond Tutu Health Foundation - Masiphumulele Site

Cape Town, South Africa

Location

Khayelitsha Vuka Research Clinic

Cape Town, South Africa

Location

Wits RHI Ward 21 Clinical Research Site

Johannesburg, South Africa

Location

Center for Community Based Research (CCBR)

Pietermaritzburg, South Africa

Location

Related Publications (19)

• Celum C, Hosek S, Tsholwana M, Kassim S, Mukaka S, Dye BJ, Pathak S, Mgodi N, Bekker LG, Donnell DJ, Wilson E, Yuha K, Anderson PL, Agyei Y, Noble H, Rose SM, Baeten JM, Fogel JM, Adeyeye A, Wiesner L, Rooney J, Delany-Moretlwe S. PrEP uptake, persistence, adherence, and effect of retrospective drug level feedback on PrEP adherence among young women in southern Africa: Results from HPTN 082, a randomized controlled trial. PLoS Med. 2021 Jun 18;18(6):e1003670. doi: 10.1371/journal.pmed.1003670. eCollection 2021 Jun.

  PMID: 34143779 BACKGROUND

• Celum CL, Bukusi EA, Bekker LG, Delany-Moretlwe S, Kidoguchi L, Omollo V, Rousseau E, Travill D, Morton JF, Mogaka F, O'Malley G, Barnabee G, van der Straten A, Donnell D, Parikh UM, Kudrick L, Anderson PL, Haberer JE, Wu L, Heffron R, Johnson R, Morrison S, Baeten JM; POWER Study Team. PrEP use and HIV seroconversion rates in adolescent girls and young women from Kenya and South Africa: the POWER demonstration project. J Int AIDS Soc. 2022 Jul;25(7):e25962. doi: 10.1002/jia2.25962.

  PMID: 35822945 BACKGROUND

• Celum CL, Gill K, Morton JF, Stein G, Myers L, Thomas KK, McConnell M, van der Straten A, Baeten JM, Duyver M, Mendel E, Naidoo K, Dallimore J, Wiesner L, Bekker LG. Incentives conditioned on tenofovir levels to support PrEP adherence among young South African women: a randomized trial. J Int AIDS Soc. 2020 Nov;23(11):e25636. doi: 10.1002/jia2.25636.

  PMID: 33247553 BACKGROUND

• Kennedy CE, Haberlen SA, Narasimhan M. Integration of sexually transmitted infection (STI) services into HIV care and treatment services for women living with HIV: a systematic review. BMJ Open. 2017 Jun 21;7(6):e015310. doi: 10.1136/bmjopen-2016-015310.

  PMID: 28637733 BACKGROUND

• Kakaire O, Byamugisha JK, Tumwesigye NM, Gamzell-Danielsson K. Prevalence and factors associated with sexually transmitted infections among HIV positive women opting for intrauterine contraception. PLoS One. 2015 Apr 10;10(4):e0122400. doi: 10.1371/journal.pone.0122400. eCollection 2015.

  PMID: 25859659 BACKGROUND

• Paavonen J, Eggert-Kruse W. Chlamydia trachomatis: impact on human reproduction. Hum Reprod Update. 1999 Sep-Oct;5(5):433-47. doi: 10.1093/humupd/5.5.433.

  PMID: 10582782 BACKGROUND

• Ville Y, Leruez M, Glowaczower E, Robertson JN, Ward ME. The role of Chlamydia trachomatis and Neisseria gonorrhoeae in the aetiology of ectopic pregnancy in Gabon. Br J Obstet Gynaecol. 1991 Dec;98(12):1260-6. doi: 10.1111/j.1471-0528.1991.tb15399.x.

  PMID: 1777459 BACKGROUND

• Stephens AJ, Aubuchon M, Schust DJ. Antichlamydial antibodies, human fertility, and pregnancy wastage. Infect Dis Obstet Gynecol. 2011;2011:525182. doi: 10.1155/2011/525182. Epub 2011 Sep 22.

  PMID: 21949601 BACKGROUND

• Amornkul PN, Vandenhoudt H, Nasokho P, Odhiambo F, Mwaengo D, Hightower A, Buve A, Misore A, Vulule J, Vitek C, Glynn J, Greenberg A, Slutsker L, De Cock KM. HIV prevalence and associated risk factors among individuals aged 13-34 years in Rural Western Kenya. PLoS One. 2009 Jul 31;4(7):e6470. doi: 10.1371/journal.pone.0006470.

  PMID: 19649242 BACKGROUND

• Masese L, Baeten JM, Richardson BA, Bukusi E, John-Stewart G, Graham SM, Shafi J, Kiarie J, Overbaugh J, McClelland RS. Changes in the contribution of genital tract infections to HIV acquisition among Kenyan high-risk women from 1993 to 2012. AIDS. 2015 Jun 1;29(9):1077-85. doi: 10.1097/QAD.0000000000000646.

  PMID: 26125141 BACKGROUND

• Steen R, Wi TE, Kamali A, Ndowa F. Control of sexually transmitted infections and prevention of HIV transmission: mending a fractured paradigm. Bull World Health Organ. 2009 Nov;87(11):858-65. doi: 10.2471/blt.08.059212.

  PMID: 20072772 BACKGROUND

• Naidoo S, Wand H, Abbai NS, Ramjee G. High prevalence and incidence of sexually transmitted infections among women living in Kwazulu-Natal, South Africa. AIDS Res Ther. 2014 Sep 15;11:31. doi: 10.1186/1742-6405-11-31. eCollection 2014.

  PMID: 25243015 BACKGROUND

• Ong JJ, Fu H, Baggaley RC, Wi TE, Tucker JD, Smith MK, Rafael S, Falconer J, Terris-Prestholt F, Mameletzis I, Mayaud P. Missed opportunities for sexually transmitted infections testing for HIV pre-exposure prophylaxis users: a systematic review. J Int AIDS Soc. 2021 Feb;24(2):e25673. doi: 10.1002/jia2.25673.

  PMID: 33605081 BACKGROUND

• Ong JJ, Baggaley RC, Wi TE, Tucker JD, Fu H, Smith MK, Rafael S, Anglade V, Falconer J, Ofori-Asenso R, Terris-Prestholt F, Hodges-Mameletzis I, Mayaud P. Global Epidemiologic Characteristics of Sexually Transmitted Infections Among Individuals Using Preexposure Prophylaxis for the Prevention of HIV Infection: A Systematic Review and Meta-analysis. JAMA Netw Open. 2019 Dec 2;2(12):e1917134. doi: 10.1001/jamanetworkopen.2019.17134.

  PMID: 31825501 BACKGROUND

• Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y, Ouellette M, Outterson K, Patel J, Cavaleri M, Cox EM, Houchens CR, Grayson ML, Hansen P, Singh N, Theuretzbacher U, Magrini N; WHO Pathogens Priority List Working Group. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018 Mar;18(3):318-327. doi: 10.1016/S1473-3099(17)30753-3. Epub 2017 Dec 21.

  PMID: 29276051 BACKGROUND

• Stewart J, Bukusi E, Sesay FA, Oware K, Donnell D, Soge OO, Celum C, Odoyo J, Kwena ZA, Scoville CW, Violette LR, Morrison S, Simoni J, McClelland RS, Barnabas R, Gandhi M, Baeten JM. Doxycycline post-exposure prophylaxis for prevention of sexually transmitted infections among Kenyan women using HIV pre-exposure prophylaxis: study protocol for an open-label randomized trial. Trials. 2022 Jun 16;23(1):495. doi: 10.1186/s13063-022-06458-8.

  PMID: 35710444 BACKGROUND

• Petousis-Harris H, Radcliff FJ. Exploitation of Neisseria meningitidis Group B OMV Vaccines Against N. gonorrhoeae to Inform the Development and Deployment of Effective Gonorrhea Vaccines. Front Immunol. 2019 Apr 9;10:683. doi: 10.3389/fimmu.2019.00683. eCollection 2019.

  PMID: 31024540 BACKGROUND

• Semchenko EA, Tan A, Borrow R, Seib KL. The Serogroup B Meningococcal Vaccine Bexsero Elicits Antibodies to Neisseria gonorrhoeae. Clin Infect Dis. 2019 Sep 13;69(7):1101-1111. doi: 10.1093/cid/ciy1061.

  PMID: 30551148 BACKGROUND

• Hadad R, Jacobsson S, Pizza M, Rappuoli R, Fredlund H, Olcen P, Unemo M. Novel meningococcal 4CMenB vaccine antigens - prevalence and polymorphisms of the encoding genes in Neisseria gonorrhoeae. APMIS. 2012 Sep;120(9):750-60. doi: 10.1111/j.1600-0463.2012.02903.x. Epub 2012 Apr 28.

  PMID: 22882265 BACKGROUND

Related Links

• Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021

MeSH Terms

Conditions

Gonorrhea; Sexually Transmitted Diseases

Interventions

4CMenB vaccine; Sodium Chloride

Condition Hierarchy (Ancestors)

Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Communicable Diseases; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Connie Celum, MD, MPH

  University of Washington

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind, Placebo-controlled
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Global Health

Model Details: 1:1 randomization to Bexsero vaccine or placebo injection, to be administered as two intramuscular (IM) doses, two months apart (at Enrollment/Visit 1 and Month 2/Visit 3). Assessment for safety events at one month following the IM doses (Visit 2 and Visit 4), followed by 5 in-clinic follow-up visits for safety, clinical, and laboratory assessments.

Study Record Dates

• First Submitted: May 11, 2024
• First Posted: June 6, 2024
• Study Start: August 14, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: July 10, 2025

Record last verified: 2025-03

Locations

ZA (5)