Clinical trial NCT02759991: Effectiveness Trial to Evaluate Protection of Pregnant Women by Hepatitis E Vaccine in Bangladesh.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis E Infection
Keywords: Hepatitis E virus
Viral Hepatitis Vaccines
Lead sponsor: Norwegian Institute of Public Health
Sponsor class: OTHER_GOV
Collaborators: name: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Sykehuset Innlandet HF
First posted: 2016-05-03
Enrollment: 19460
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 39
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1. 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.
2. 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.
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Effectiveness of HEV vaccine in preventing HEV diseases among women in Bangladesh
timeFrame: 2 years
Secondary outcomes:
measure: To determine the safety of HEV vaccine in Bangladeshi women of childbearing age
timeFrame: 2 years
measure: To determine the immunogenicity of HEV vaccine in Bangladeshi women of childbearing age
timeFrame: 2 years
measure: Effectiveness of HEV vaccine in preventing HEV disease in non-pregnant Bangladeshi women of childbearing age
timeFrame: 2 years
measure: Estimate serological correlates of protection
timeFrame: 2 years
measure: Assess the feasibility, acceptability and cost-effectiveness of HEV vaccination of women of childbearing age in rural Bangladesh
timeFrame: 2 years
measure: Investigate acute HEV cases virologically, clinically and immunologically in relation to outcome.
timeFrame: 2 years
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: International Centre for Diarrhoeal Disease Research, Bangladesh
Study officials:
affiliation: Norwegian Institute of Public Health
name: Susanne Dudman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh, Centre for Child and Adolescent Health
name: K Zaman, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zaman K, Dudman S, Stene-Johansen K, Qadri F, Yunus M, Sandbu S, Gurley ES, Overbo J, Julin CH, Dembinski JL, Nahar Q, Rahman A, Bhuiyan TR, Rahman M, Haque W, Khan J, Aziz A, Khanam M, Streatfield PK, Clemens JD. HEV study protocol : design of a cluster-randomised, blinded trial to assess the safety, immunogenicity and effectiveness of the hepatitis E vaccine HEV 239 (Hecolin) in women of childbearing age in rural Bangladesh. BMJ Open. 2020 Jan 19;10(1):e033702. doi: 10.1136/bmjopen-2019-033702.