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

NCT ID: NCT02759991

Last Updated: 2024-08-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

19460 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-02

Study Completion Date

2019-09-30

Brief Summary

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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

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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.

Conditions

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Hepatitis E Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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HEV vaccine

Hecolin, 0.6 ml intramuscular injection day 0, 1 month and 6 months.

Group Type ACTIVE_COMPARATOR

Hecolin

Intervention Type DRUG

0.6ml Hecolin vaccine im. on day 0, 1 month and 6 months.

HBV vaccine

Hepa-B, 1 ml intramuscular injection day 0, 1 month and 6 months.

Group Type PLACEBO_COMPARATOR

Hepa-B

Intervention Type DRUG

1ml Hepa-B vaccine im. on day 0, 1 month and 6 months.

Interventions

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Hecolin

0.6ml Hecolin vaccine im. on day 0, 1 month and 6 months.

Intervention Type DRUG

Hepa-B

1ml Hepa-B vaccine im. on day 0, 1 month and 6 months.

Intervention Type DRUG

Other Intervention Names

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HEV 239 Hepatitis B virus (HBV) vaccine

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* Pregnancy
* Allergic to vaccine components
* Serious chronic diseases
* Acute illness
Minimum Eligible Age

16 Years

Maximum Eligible Age

39 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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International Centre for Diarrhoeal Disease Research, Bangladesh

OTHER

Sponsor Role collaborator

Sykehuset Innlandet HF

OTHER

Sponsor Role collaborator

Norwegian Institute of Public Health

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Susanne Dudman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Norwegian Institute of Public Health

K Zaman, PhD

Role: PRINCIPAL_INVESTIGATOR

International Centre for Diarrhoeal Disease Research, Bangladesh, Centre for Child and Adolescent Health

Locations

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International Centre for Diarrhoeal Disease Research, Bangladesh

Dhaka, , Bangladesh

Site Status

Countries

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Bangladesh

References

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Overbo J, Dembinski JL, Nilsen TR, Sriranganathan V, Dimova-Svetoslavova VP, Aziz A, Zaman K, Julin CH, Qadri F, Stene-Johansen K, Bhuiyan TR, Haque W, Dudman S. Cellular and Humoral Immune Profiles After Hepatitis E Vaccination and Infection. Viruses. 2025 Jun 26;17(7):901. doi: 10.3390/v17070901.

Reference Type DERIVED
PMID: 40733519 (View on PubMed)

Aziz AB, Dudman S, Julin CH, Ahmmed F, Stene-Johansen K, Sandbu S, Overbo J, Dembinski JL, Wisloff T, Rana S, Basunia AH, Haque W, Qadri F, Zaman K, Clemens JD. Receipt of hepatitis E vaccine and fetal loss in rural Bangladesh: further analysis of a double-blind, cluster-randomised, controlled trial. Lancet Glob Health. 2024 Aug;12(8):e1300-e1311. doi: 10.1016/S2214-109X(24)00193-1.

Reference Type DERIVED
PMID: 39030061 (View on PubMed)

Zaman K, Julin CH, Aziz AB, Stene-Johansen K, Yunus M, Qadri F, Gurley ES, Sandbu S, Overbo J, Dembinski JL, Laake I, Bhuiyan TR, Rahman M, Haque W, Khanam M, Clemens JD, Dudman S. Safety and effectiveness of a recombinant hepatitis E vaccine in women of childbearing age in rural Bangladesh: a phase 4, double-blind, cluster-randomised, controlled trial. Lancet Glob Health. 2024 Aug;12(8):e1288-e1299. doi: 10.1016/S2214-109X(24)00192-X.

Reference Type DERIVED
PMID: 39030060 (View on PubMed)

Overbo J, Aziz A, Zaman K, Clemens J, Halle Julin C, Qadri F, Stene-Johansen K, Biswas R, Islam S, Rahman Bhuiyan T, Haque W, Sandbu S, Elahee ME, Ali M, Dembinski JL, Dudman S. Immunogenicity and safety of a two-dose regimen with hepatitis E virus vaccine in healthy adults in rural Bangladesh: A randomized, double-blind, controlled, phase 2/pilot trial. Vaccine. 2023 Jan 27;41(5):1059-1066. doi: 10.1016/j.vaccine.2022.12.064. Epub 2023 Jan 2.

Reference Type DERIVED
PMID: 36599736 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31959609 (View on PubMed)

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

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61067

Identifier Type: -

Identifier Source: org_study_id

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