Effectiveness Trial to Evaluate Protection of Pregnant Women by Hepatitis E Vaccine in Bangladesh.

Phase 4

Completed

• Conditions: Hepatitis E Infection
• Interventions: Drug: Hecolin; Drug: Hepa-B

• Registration Number: NCT02759991
• Lead Sponsor: Norwegian Institute of Public Health

Brief 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.

Study Timeline

• Study First Submitted: 2016-03-21
• Study First Submitted QC: 2016-04-29
• Study First Posted: 2016-05-03
• Study Start: 2017-10-02
• Primary Completion: 2019-09-30
• Study Completion: 2019-09-30
• Status Verified: 2020-10
• Last Update Submitted: 2024-08-12
• Last Update Posted: 2024-08-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 19460

Inclusion Criteria

• Women aged 16-39 years
• Living in Matlab area

Exclusion Criteria

• Pregnancy
• Allergic to vaccine components
• Serious chronic diseases
• Acute illness

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HEV vaccine	Hecolin	Hecolin, 0.6 ml intramuscular injection day 0, 1 month and 6 months.
HBV vaccine	Hepa-B	Hepa-B, 1 ml intramuscular injection day 0, 1 month and 6 months.

Primary Outcome Measures

Name	Time	Method
Effectiveness of HEV vaccine in preventing HEV diseases among women in Bangladesh	2 years	To determine the effectiveness of hepatitis E virus (HEV) vaccine in preventing HEV disease during pregnancy among women in rural Bangladesh

Secondary Outcome Measures

Name	Time	Method
To determine the safety of HEV vaccine in Bangladeshi women of childbearing age	2 years	Number of participants with adverse events related to vaccination as assessed by CTCAE v4.0
To determine the immunogenicity of HEV vaccine in Bangladeshi women of childbearing age	2 years	Number of participants who seroconvert after three doses
Estimate serological correlates of protection	2 years	Assess the anti-HEV IgG levels before and one month after the last dose of vaccine for primary vaccine response and record if any HEV disease occurs.
Investigate acute HEV cases virologically, clinically and immunologically in relation to outcome.	2 years	Examine acute HEV cases in relation to severity of illness and immunological responses
Effectiveness of HEV vaccine in preventing HEV disease in non-pregnant Bangladeshi women of childbearing age	2 years	To determine the effectiveness of hepatitis E virus (HEV) vaccine in preventing HEV disease in participants
Assess the feasibility, acceptability and cost-effectiveness of HEV vaccination of women of childbearing age in rural Bangladesh	2 years	Analyse cost per disability, adjusted life year and quality adjusted life year

Trial Locations

Locations (1)

International Centre for Diarrhoeal Disease Research, Bangladesh; 🇧🇩 Dhaka, Bangladesh