Evaluating Immunogenicity of a Birth Dose of HBV Vaccine in the DRC

NCT03897946 | Completed Phase 4

• 1 other identifier: 18-2793
• Study Type: interventional
• Target: 569
• Locations: 1 country
• Sites: 1

Brief Summary

This project will assess the immunogenicity of a birth dose of hepatitis B vaccine in hepatitis B-exposed and hepatitis B-unexposed infants in Kinshasa, Democratic Republic of the Congo. A better understanding of the protection offered by the addition of birth dose vaccine to the EPI schedule is necessary in order to promote universal adoption of a birth dose vaccine in the DRC and throughout SSA.

Conditions

Hepatitis B

Outcome Measures

Primary Outcomes (1)

• Proportion of Infants with Protective Immunity

  Protective immunity is defined as quantitative HBsAb ≥ 10 milli-International unit(mIU)/mL

  At 12 months of age

Secondary Outcomes (1)

• Proportion of Infants with Adverse Reactions to the Birth Dose Hepatitis B Vaccine

  Within 2-3 days after birth

Study Arms (3)

Group A: Hepatitis B exposed, with birth dose

EXPERIMENTAL

The 100 HBV-exposed (born to HBsAg-positive mothers) infants who are already enrolled in the parent AVERT study will also be enrolled in the current study, as the "HBV-exposed cohort" (Group A). These exposed infants will not receive additional interventions on top of the AVERT study since they will already be receiving a birth dose vaccine through the AVERT study.

Biological: Birth dose hepatitis B vaccine

Group B: Hepatitis B unexposed, no birth dose

NO INTERVENTION

For the "HBV-unexposed cohort" in this study, the investigators will enroll 200 infants born to HBsAg-negative mothers. Half (100) of these infants will receive the routine three-dose series of HBV vaccine according to the standard EPI schedule in the DRC with no additional birth dose vaccine (Group B).

Group C: Hepatitis B unexposed, with birth dose

EXPERIMENTAL

Group C will consist of the other half (100) of infants in the "HBV-unexposed cohort" who will receive four doses of HBV vaccine including a birth dose vaccine prior to the routine EPI schedule.

Biological: Birth dose hepatitis B vaccine

Interventions

Birth dose hepatitis B vaccine BIOLOGICAL

Groups A and C will receive a birth dose of hepatitis B vaccine within 24 hours of life.

Group A: Hepatitis B exposed, with birth dose; Group C: Hepatitis B unexposed, with birth dose

Eligibility Criteria

• Age: Up to 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• HBsAg+ mothers and HBsAg- mothers will be recruited from the cohort screened during the AVERT study at 2 maternity centers (Binza and Kingasani) in Kinshasa.

You may not qualify if:

• Any women who do not intend to stay in Kinshasa for prenatal care through delivery or who deliver at a facility other than Binza or Kingasani
• Women \<18 years of age
• INFANTS
• Infants born to HBsAg-positive and HBsAg-negative women who receive care at Binza and Kingasani maternity centers will be recruited for participation in this study.
• HIV-exposed infants (those born to HIV-positive mothers) will be excluded given an expected difference in immune response in these infants and inability to recruit enough HIV-exposed infants to be able to detect these differences in immune response
• HBV-unexposed infants weighing \<2,000 grams at birth will not be eligible to receive the birth HBV vaccine. (HBV-exposed infants receive the birth dose vaccine regardless of birth weight because the potential benefit of preventing mother-to-child transmission outweighs the potential risk of vaccination in a low birthweight infant. The research team recognizes that Group B may include a disproportionate number of low birthweight infants compared to Group C, but will account for this in post-hoc analyses and if need be, will exclude low birthweight infants from the analysis to account for potential bias).
• Infants born at a facility other than one of the two maternity centers

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• The American Society of Tropical Medicine and Hygiene: collaborator
• Burroughs Wellcome: collaborator

Study Sites (1)

Binza and Kingasani Maternity Centers

Kinshasa, Democratic Republic of the Congo

Location

Related Publications (15)

• O'Hara GA, McNaughton AL, Maponga T, Jooste P, Ocama P, Chilengi R, Mokaya J, Liyayi MI, Wachira T, Gikungi DM, Burbridge L, O'Donnell D, Akiror CS, Sloan D, Torimiro J, Yindom LM, Walton R, Andersson M, Marsh K, Newton R, Matthews PC. Hepatitis B virus infection as a neglected tropical disease. PLoS Negl Trop Dis. 2017 Oct 5;11(10):e0005842. doi: 10.1371/journal.pntd.0005842. eCollection 2017 Oct. No abstract available.

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• Edmunds WJ, Medley GF, Nokes DJ, O'Callaghan CJ, Whittle HC, Hall AJ. Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas. Epidemiol Infect. 1996 Oct;117(2):313-25. doi: 10.1017/s0950268800001497.

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• Wilson P, Parr JB, Jhaveri R, Meshnick SR. Call to Action: Prevention of Mother-to-Child Transmission of Hepatitis B in Africa. J Infect Dis. 2018 Mar 28;217(8):1180-1183. doi: 10.1093/infdis/jiy028.

  PMID: 29351639 BACKGROUND

• Andersson MI, Rajbhandari R, Kew MC, Vento S, Preiser W, Hoepelman AI, Theron G, Cotton M, Cohn J, Glebe D, Lesi O, Thursz M, Peters M, Chung R, Wiysonge C. Mother-to-child transmission of hepatitis B virus in sub-Saharan Africa: time to act. Lancet Glob Health. 2015 Jul;3(7):e358-9. doi: 10.1016/S2214-109X(15)00056-X. No abstract available.

  PMID: 26087980 BACKGROUND

• Klingler C, Thoumi AI, Mrithinjayam VS. Cost-effectiveness analysis of an additional birth dose of Hepatitis B vaccine to prevent perinatal transmission in a medical setting in Mozambique. Vaccine. 2012 Dec 17;31(1):252-9. doi: 10.1016/j.vaccine.2012.08.007. Epub 2012 Aug 15.

  PMID: 22902676 BACKGROUND

• Poovorawan Y, Sanpavat S, Pongpunlert W, Chumdermpadetsuk S, Sentrakul P, Safary A. Protective efficacy of a recombinant DNA hepatitis B vaccine in neonates of HBe antigen-positive mothers. JAMA. 1989 Jun 9;261(22):3278-81.

  PMID: 2523981 BACKGROUND

• Wong VC, Ip HM, Reesink HW, Lelie PN, Reerink-Brongers EE, Yeung CY, Ma HK. Prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg by administration of hepatitis-B vaccine and hepatitis-B immunoglobulin. Double-blind randomised placebo-controlled study. Lancet. 1984 Apr 28;1(8383):921-6. doi: 10.1016/s0140-6736(84)92388-2.

  PMID: 6143868 BACKGROUND

• Tsega E, Tafesse B, Nordenfelt E, Wolde-Hawariat G, Hansson BG, Lindberg J. Immunogenicity of hepatitis B vaccine simultaneously administered with the expanded programme on immunisation (EPI). J Med Virol. 1990 Dec;32(4):232-5. doi: 10.1002/jmv.1890320407.

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• Abu-Raya B, Kollmann TR, Marchant A, MacGillivray DM. The Immune System of HIV-Exposed Uninfected Infants. Front Immunol. 2016 Sep 28;7:383. doi: 10.3389/fimmu.2016.00383. eCollection 2016.

  PMID: 27733852 BACKGROUND

• Njom Nlend AE, Nguwoh PS, Ngounouh CT, Tchidjou HK, Pieme CA, Otele JM, Penlap V, Colizzi V, Moyou RS, Fokam J. HIV-Infected or -Exposed Children Exhibit Lower Immunogenicity to Hepatitis B Vaccine in Yaounde, Cameroon: An Appeal for Revised Policies in Tropical Settings? PLoS One. 2016 Sep 22;11(9):e0161714. doi: 10.1371/journal.pone.0161714. eCollection 2016.

  PMID: 27656883 BACKGROUND

• Tulenko SE, Ngimbi P, Mwandagalirwa K, Tabala M, Matondo J, Ntambua S, Mbonze N, Mbendi C, Luhata C, Jhaveri R, Edwards JK, Becker-Dreps S, Moormann AM, Kaba D, Yotebieng M, Parr JB, Gower EW, Thompson P. Immunogenicity of a Birth Dose of Hepatitis B Vaccine in Kinshasa, Democratic Republic of Congo: A Randomised, Controlled Trial. J Viral Hepat. 2024 Dec;31(12):795-807. doi: 10.1111/jvh.14003. Epub 2024 Sep 24.

  PMID: 39314125 DERIVED

Related Links

• World Health Organization Global Hepatitis Report, 2017
• Congo Democratic Republic: Demographic and Health Survey, 2013-2014 - Final Report

MeSH Terms

Conditions

Hepatitis B

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Steven R Meshnick, MD, PhD

  UNC-Chapel Hill

  STUDY DIRECTOR

• Peyton J Thompson, MD

  UNC-Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participants and care providers will not be masked, but the investigators and data analysts will be masked to group allocation.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2019
• First Posted: April 1, 2019
• Study Start: August 20, 2019
• Primary Completion: February 5, 2021
• Study Completion: February 5, 2021
• Last Updated: March 3, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)