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

Hepatitis E Infection Clinical Trial

Official title:

An Effectiveness Trial (Phase IV) to Evaluate Protection of Pregnant Women by Hepatitis E Virus (HEV) Vaccine in Bangladesh and Risk Factors for Severe HEV Infection.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02759991
• Other study ID #: 61067
• Status: Completed
• Phase: Phase 4
• Start date: October 2, 2017
• Est. completion date: September 30, 2019

Study information

• Verified date: October 2020
• Source: Norwegian Institute of Public Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19460
• Est. completion date: September 30, 2019
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 16 Years to 39 Years

Eligibility

Inclusion Criteria:

• Women aged 16-39 years

• Living in Matlab area

Exclusion Criteria:

• Pregnancy

• Allergic to vaccine components

• Serious chronic diseases

• Acute illness

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis E
• Hepatitis E Infection
• Infection

Intervention

Drug:
• Hecolin
0.6ml Hecolin vaccine im. on day 0, 1 month and 6 months.
• Hepa-B
1ml Hepa-B vaccine im. on day 0, 1 month and 6 months.

Locations

Country	Name	City	State
Bangladesh	International Centre for Diarrhoeal Disease Research, Bangladesh	Dhaka

Sponsors (3)

Lead Sponsor	Collaborator
Norwegian Institute of Public Health	International Centre for Diarrhoeal Disease Research, Bangladesh, Sykehuset Innlandet HF

Country where clinical trial is conducted

Bangladesh, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effectiveness of HEV vaccine in preventing HEV diseases among women in Bangladesh	To determine the effectiveness of hepatitis E virus (HEV) vaccine in preventing HEV disease during pregnancy among women in rural Bangladesh	2 years
Secondary	To determine the safety of HEV vaccine in Bangladeshi women of childbearing age	Number of participants with adverse events related to vaccination as assessed by CTCAE v4.0	2 years
Secondary	To determine the immunogenicity of HEV vaccine in Bangladeshi women of childbearing age	Number of participants who seroconvert after three doses	2 years
Secondary	Effectiveness of HEV vaccine in preventing HEV disease in non-pregnant Bangladeshi women of childbearing age	To determine the effectiveness of hepatitis E virus (HEV) vaccine in preventing HEV disease in participants	2 years
Secondary	Estimate serological correlates of protection	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.	2 years
Secondary	Assess the feasibility, acceptability and cost-effectiveness of HEV vaccination of women of childbearing age in rural Bangladesh	Analyse cost per disability, adjusted life year and quality adjusted life year	2 years
Secondary	Investigate acute HEV cases virologically, clinically and immunologically in relation to outcome.	Examine acute HEV cases in relation to severity of illness and immunological responses	2 years