Antiviral Prophylaxis and Infant Vaccination to Prevent Perinatal Hepatitis B Infection

February 14, 2024 updated by: GONZAGUE JOURDAIN, Institut de Recherche pour le Developpement

A Maternal Short Course of Tenofovir Disoproxil Fumarate and Infant Vaccine to Prevent Mother-to-child Transmission of Hepatitis B Virus

Most new hepatitis B virus (HBV) infections are acquired perinatally. In this study, pregnant women with HBsAg and HBeAg will receive tenofovir disoproxil fumarate during the last trimester of pregnancy and for two months following delivery. Their infants will receive hepatitis B (HB) immunization, starting with a first dose soon after birth. We hypothesize that the risk of mother-to-child transmission of HBV will be lower than 2%. The results of the study will help define policy to manage HBV infected pregnant women to prevent perinatal transmission.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a prospective multi-center, multi-country (Thailand and Lao PDR), open-label, single arm clinical trial in HBsAg and HBeAg positive pregnant women (from 28 weeks until one year postpartum) and their infants (until 18 months of age). Pregnant women with HBsAg and HBeAg will receive tenofovir disoproxil fumarate 300 mg once daily from 28 weeks of pregnancy until two months postpartum. Their infants will receive hepatitis B (HB) immunization, starting with the first dose soon after birth.

The study aims to show that substituting maternal antiviral treatment for infant HBIg can be favorably considered in settings where HBIg plus vaccine has been used as well as in settings where only vaccine is used. A significant improvement over the standard HBIg + vaccine strategy would be that adding an antiviral strategy results in less than 2% transmission. A total of 499 women and their infants will be enrolled in public hospitals in Thailand and Lao PDR.

The study will be monitored by a Data and Safety Monitoring Board (DSMB) at least annually.

Study Type

Interventional

Enrollment (Actual)

504

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Lao People's Democratic Republic
      • Champasak, Lao People's Democratic Republic
        • Champasak Hospital
      • Luang Prabang, Lao People's Democratic Republic
        • Luang Prabang Provincial Hospital
      • Savannakhet, Lao People's Democratic Republic
        • Savannakhet Provincial hospital
      • Sayaboury, Lao People's Democratic Republic
        • Sayaboury Hospital
      • Vientiane, Lao People's Democratic Republic
        • 103 Hospital
      • Vientiane, Lao People's Democratic Republic
        • Mahosot Hospital
      • Vientiane, Lao People's Democratic Republic
        • Mother and Newborn Hospital
      • Vientiane, Lao People's Democratic Republic
        • Setthathirath Hospital
  • Thailand
      • Bangkok, Thailand, 10230
        • Nopparat Rajathanee Hospital
      • Chanthaburi, Thailand, 22000
        • Prapokklao Hospital
      • Chiang Mai, Thailand, 50180
        • Nakornping Hospital
      • Chiang Mai, Thailand, 50100
        • Health Promotion Center Region 1
      • Chiang Rai, Thailand, 57000
        • Chiangrai Prachanukroh Hospital
      • Chon Buri, Thailand, 20000
        • Chonburi Hospital
      • Chon Buri, Thailand, 20150
        • Banglamung Hospital
      • Lampang, Thailand, 52000
        • Lampang Hospital
      • Lamphun, Thailand, 51000
        • Lamphun Hospital
      • Samut Prakan, Thailand, 10280
        • Samutprakarn Hospital
      • Samut Sakhon, Thailand, 74000
        • Samutsakhon Hospital
    • Phayao
      • Chiang Kham, Phayao, Thailand, 56110
        • Chiang Kham Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pregnancy
  • Age ≥18 years
  • Negative HIV antibody test during current pregnancy
  • Positive HBsAg test during current pregnancy
  • Positive HBeAg using a rapid test during current pregnancy
  • Absence of clinical symptoms of liver disease
  • Gestational age of 28 weeks (+/- 7 days) based on the obstetrician judgment guided by the review of the date of last menstruation period.
  • Willing and able to provide written informed consent
  • Agreeing to bring her infants(s) at the planned study visits at one of the study site until the last visit (18 months after birth) and to inform the site investigators if plans to move to another place and not be able to return to the clinic
  • Understand the need for adequate infant immunization for her infant(s) and accept that blood draws will be performed to determine the infant HBV infection status

Exclusion Criteria:

  • Receipt of anti-HBV antivirals at any time during the last 9 months
  • Known liver cirrhosis or evidence of hepatocellular carcinoma
  • Creatinine clearance <50 ml/min, calculated using the Cockcroft-Gault formula
  • Confirmed dipstick proteinuria >1+ (>30 mg/dL) or normoglycemic glycosuria
  • Evidence of pre-existing fetal anomalies incompatible with life
  • Any concomitant condition or treatment that, in the view of the clinical site investigator, would contraindicate participation or compromise adherence to treatment and satisfactory follow up in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Infant hepatitis B infection status
Time Frame: Six months of age
HBsAg positive confirmed by PCR detection of HBV DNA.
Six months of age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maternal HBV DNA changes
Time Frame: From enrollment until end of study treatment scheduled 2 months after delivery
Description of the effect of tenofovir disoproxil fumarate on maternal HBV DNA levels
From enrollment until end of study treatment scheduled 2 months after delivery
Infant levels of anti-HBs antibodies
Time Frame: At 1, 2, 4, 6, and 12 months of age
Levels of anti-HBs antibodies in infants in the absence of HBIg administration at birth
At 1, 2, 4, 6, and 12 months of age
HBV infection status in all infants regardless of maternal response to study treatment
Time Frame: At 6 months of age
HBsAg positive confirmed by PCR detection of HBV DNA in all infants, i.e. including those born to women with unsatisfactory virological response to study treatment
At 6 months of age
Serious adverse events
Time Frame: From enrollment until 12 months postpartum
Occurrence of maternal serious adverse events (ICH SAEs) including DAIDS grade 4 signs and symptoms regardless of their relatedness to the study treatment
From enrollment until 12 months postpartum
Serious adverse events
Time Frame: From birth until 12 months of age
Occurrence of infant serious adverse events (ICH SAEs) including DAIDS grade 4 signs and symptoms regardless of their relatedness to the study treatment
From birth until 12 months of age
Preterm live births
Time Frame: Delivery
Proportion of neonates born alive before 37 weeks of pregnancy
Delivery
Low birth weight
Time Frame: Delivery
Proportion of neonates born alive with birth weight of 2,499 g or less, regardless of gestational age
Delivery
Active or previous transient infection in children
Time Frame: At 18 months of age
Detection of anti-HBc antibodies among all infants
At 18 months of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut de Recherche pour le Developpement

Collaborators

Chiang Mai University
Ministry of Health, Thailand
Ministry of Health, Lao PDR

Investigators

  • Principal Investigator: Gonzague Jourdain, MD, PhD, Institut de Recherche pour l e Développement

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 2, 2018

Primary Completion (Actual)

January 13, 2023

Study Completion (Estimated)

April 30, 2024

Study Registration Dates

First Submitted

November 6, 2017

First Submitted That Met QC Criteria

November 11, 2017

First Posted (Actual)

November 17, 2017

Study Record Updates

Last Update Posted (Actual)

February 16, 2024

Last Update Submitted That Met QC Criteria

February 14, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • iTAP-2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

We are willing to share our data with other investigators, for example for meta-analysis, in order to answer important research questions requiring large datasets, after completion of the original research plan including substudies. Data-sharing agreements will include: an approval of the research plan by appropriate ethics committees, a commitment to using data for research purposes only and to securing the data or/and the samples using appropriate methods. We will consult as needed with the funding agency the practical aspects of data sharing.

Data used for publications will be released in a timely manner. De-identified study data could be accessible through a website that allows querying such as the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Data and Specimen Hub or DASH (dash.nichd.nih.gov/).

IPD Sharing Time Frame

At the same time as related publications

IPD Sharing Access Criteria

See Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Data and Specimen Hub or DASH

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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