Tenofovir in Early Pregnancy to Prevent Mother-to-child Transmission of Hepatitis B Virus

February 3, 2023 updated by: Johns Hopkins Bloomberg School of Public Health

Prevention of Mother-to-child Transmission of Hepatitis B Virus: a One Arm, Open Label Intervention Study to Estimate the Optimal Timing of Tenofovir (TDF) in Pregnancy

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains the major mode of transmission in most high and intermediate HBV endemic areas, despite existing WHO immunoprophylaxis recommendations. This immunoprophylaxis regimen, if given optimally, can prevent 75-80% of HBV MTCT, but optimal implementation is difficult because it requires administering monovalent HBV vaccine and hepatitis B immunoglobulin (HBIg) within 24 hours of birth. Due to the barriers of giving HBIg, the World Health Organization (WHO) states, "…owing to concerns related to supply, safety and cost, the use of HBIg is not feasible in most settings." Clearly, global control of HBV transmission will require improved MTCT prevention. Therefore, the investigators hypothesize that treating HBV early in pregnancy will lead to undetectable HBV DNA levels at delivery and prevention of MTCT of HBV without HBIg; a concept that has already been proven with HIV. Tenofovir disoproxil fumarate (TDF), an approved anti-HBV drug, is promising to prevent MTCT of HBV due to its high potency against hepatitis B and its safety record in pregnant women. A randomized, controlled clinical trial (RCT) will be necessary to determine if TDF given to HBV-infected pregnant women early in pregnancy plus vaccine to the newborn can decrease MTCT of HBV without HBIg. However, before embarking on a RCT, several critical knowledge gaps need to be addressed including the ideal timing for TDF initiation. The purpose of this proposal is to address these knowledge gaps.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators hypothesize that anti-HBV therapy given in the late first or early second trimester achieves undetectable HBV DNA at delivery in >=95% of pregnant women with chronic hepatitis B. The one-arm, open-label, interventional study aims: 1, To estimate the time to complete HBV DNA suppression (<100 IU/ml) in 170 HBV DNA positive women who start TDF in the late first or early second trimester; and to estimate the proportion of women with HBV DNA <100 IU/ml at delivery. 2, To address potential barriers to and the efficacy of implementing TDF in early pregnancy to prevent mother-to-child transmission of hepatitis B. The investigators will measure potential barriers to acceptability and effectiveness of this intervention: adherence, potential hepatitis B flares in mothers (safety), and the proportion of hepatitis B infections in the offspring at 1 year of age (efficacy).

Study Type

Interventional

Enrollment (Actual)

98

Phase

  • Phase 2
  • Phase 1

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

  • Thailand
      • Mae Sot, Thailand
        • Shoklo Malaria Research Unit

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

16 years to 49 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Pregnant women aged 18 and over
  • HBsAg positive
  • In the 12th-20th week of pregnancy
  • Willing to take TDF daily during pregnancy
  • Providing written informed consent
  • Plans to deliver at Shoklo Malaria Research Unit (SMRU)
  • Able and willing to comply with study requirements

Exclusion Criteria:

  • Anti-HIV positive
  • Negative qualitative HBV DNA if HBeAg negative
  • On immunosuppressive therapy
  • Elevated creatinine
  • History of kidney disease
  • Short cervix
  • History of pregnancy complications or prior pre-term labor

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Tenofovir Disoproxil Fumarate
Women early in pregnancy (end of first or beginning second trimester) will be treated with TDF to determine the efficacy of this strategy to bring >=95% of women to undetectable HBV DNA levels at delivery.
Drug: Tenofovir Disoproxil Fumarate
300 mg daily
Other Names:
  • Viread

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The time (from inclusion through delivery; up to 6 months) to HBV DNA suppression (<100 IU/ml)
Time Frame: Up to 9 months
HBV DNA will be monitored every month
Up to 9 months
The proportion of women with undetectable HBV DNA at delivery
Time Frame: At delivery
HBV DNA will be monitored at delivery.
At delivery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of hepatitis B flares in mothers postpartum
Time Frame: Monthly measured for 3 months after stopping TDF.
All women will continue on study for 3 months after stopping TDF to measure their alanine aminotransferase (ALT) and aspartate aminotransferase (AST) monthly to detect a flare, which will be defined as >5x baseline or >10x the upper limit of normal. If at the end of the 3 months, there has been no change in ALT and AST, then the mothers will be discharged from the study. If there is an increase in liver enzymes but not a true flare, they will be followed for an additional 3 months with monthly ALT testing.
Monthly measured for 3 months after stopping TDF.
The proportion of women who adhered to TDF treatment during the course of the study (from inclusion through 1 month after delivery; up to 7 months; drug levels)
Time Frame: Up to 9 months
Measurement of tenofovir drug levels
Up to 9 months
The proportion of women who adhered to TDF treatment during the course of the study (from inclusion through 1 month after delivery; up to 7 months; drug accountability)
Time Frame: Up to 9 months
Drug accountability using standard methods (subtracting the number of tablets left from the number of tablets distributed).
Up to 9 months
The proportion of women who adhered to TDF treatment during the course of the study (from inclusion through 1 month after delivery; up to 7 months; questionnaire)
Time Frame: Up to 9 months
All women will be surveyed at monthly visits and at birth to measure adherence including actionable barriers.
Up to 9 months
The proportion of hepatitis B infections in the offspring at 1 year of age
Time Frame: Between month 2 and 12 month
Testing for HBsAg in children between 2 and 12 months of age.
Between month 2 and 12 month

Collaborators and Investigators

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

Sponsor

Johns Hopkins Bloomberg School of Public Health

Collaborators

University of Oxford
Thrasher Research Fund
Chiang Mai University
Shoklo Malaria Research Unit

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

May 24, 2018

Primary Completion (ACTUAL)

January 31, 2023

Study Completion (ACTUAL)

January 31, 2023

Study Registration Dates

First Submitted

December 8, 2016

First Submitted That Met QC Criteria

December 13, 2016

First Posted (ESTIMATE)

December 16, 2016

Study Record Updates

Last Update Posted (ACTUAL)

February 6, 2023

Last Update Submitted That Met QC Criteria

February 3, 2023

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JHSPH-TDF

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The investigators are currently developing an individual participant data (IPD) sharing plan.

IPD Sharing Time Frame

Data will become available 6 months after publication of the main report.

IPD Sharing Access Criteria

Permission by corresponding author

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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