Effectiveness Trial to Evaluate Protection of Pregnant Women by Hepatitis E Vaccine in Bangladesh.
Condition: Hepatitis E Infection
MeSH terms: Infections; Hepatitis A; Hepatitis E; Hepatitis
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of the study is to determine the effectiveness of hepatitis E virus vaccine given in
      women of child bearing age in preventing HEV disease during pregnancy among women in rural
      Bangladesh.
    

Detailed description: 
      Hepatitis E virus (HEV) infection is endemic in Bangladesh, causing severe or fatal
      complications in pregnant women. This GLOBVAC funded project aims to assess the safety,
      feasibility, acceptability, immunogenicity, effectiveness, and cost-effectiveness of the HEV
      vaccine (Hecolin, Innovax, China) when given women of childbearing age in a rural area in
      Bangladesh (Matlab). The vaccine has been shown to be both effective and safe in the general
      adult population in China, but there is insufficient data about its efficacy among pregnant
      women, the group with most to gain from vaccination.

      The research plan has been carefully designed and will be conducted by a multidisciplinary
      team of researchers at International Centre for Diarrhoeal Disease Research (iccdr,b) in
      Bangladesh and the Norwegian Institute of Public Health and Innlandet Hospital Trust in
      Norway. Over a period of 2 years, 20,745 non-pregnant women will be recruited and will
      receive either the hepatitis E vaccine or a hepatitis B vaccine (control group). All women
      who develop hepatitis E symptoms will be tested for the disease. Those who become pregnant
      during the study will also be checked and tested during regular home visits. Clinical
      outcomes and vaccine adverse events will be closely monitored.

      In order to evaluate the initial safety profile and immunogenicity of the vaccine, a pilot
      study was completed during summer 2017. A total of 100 non-pregnant females and males, aged
      16-39, were enrolled and randomly received either the hepatitis E vaccine or a hepatitis B
      vaccine. Participants were vaccinated on day 0 and day 30, and blood, dried blood spots (DBS)
      and saliva samples were collected on day 0 and day 60 for use in laboratory assay validation
      and serological and cellular immunogenicity analyses. Following each vaccination, home visits
      were carried out for 7 days to record adverse reactions. No serious adverse reactions were
      observed, and only a few mild local adverse reactions were recorded which all resolved
      without sequela. Preliminary immunogenicity results, showed that 44 participants had
      seroconverted (HEV), after just two doses of the vaccine. Furthermore, during this pilot
      study the implementation of protocols and procedures for all stages of the trial were tested
      in preparation for the start of the main trial.

      Additionally, hepatitis surveillance in Matlab has been initiated in order to establish an
      HEV surveillance system. All women aged 16-39 are included in the surveillance, and requested
      to contact icddr,b staff if they experience jaundice of any duration, or other symptoms of
      hepatitis. Patients admitted to Matlab hospital have a blood sample taken for hepatitis
      diagnostics, and acute HEV cases are investigated virologically, clinically and
      immunologically. Household visits occur bi-weekly to document any possible hepatitis cases.
    

Intervention name(s): Hecolin; Hepa-B
Intervention type(s): Drug; Drug
Intervention description(s): 0.6ml Hecolin vaccine im. on day 0, 1 month and 6 months.; 1ml Hepa-B vaccine im. on day 0, 1 month and 6 months.
Other intervention name(s): HEV 239; Hepatitis B virus (HBV) vaccine
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Pilot study completed in 2017 with 100 participants, 50 women and 50 men aged 16-39, randomized to be vaccinated with either 2 doses of Hecolin or Hepa-B. These 100 participants are not included in the main trial.
Main clinical trial designed to enroll 20.745 women aged 16-39 years living in Matlab area. All participants randomized to be vaccinated with either Hecolin or Hepa-B three doses.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Hepatitis E virus; Viral Hepatitis Vaccines