Tenofovir in Late Pregnancy to Prevent Vertical Transmission of Hepatitis B Virus

December 6, 2019 updated by: New Discovery LLC

Tenofovir Disoproxil Fumarate in Late Pregnancy to Prevent Vertical Transmission of Hepatitis B Virus in Highly Viremic Mothers

Immunoprophylaxis failure of hepatitis B virus (HBV) leading to vertical transmission remains a concern and has been reported in approximately 8-15% of infants born to hepatitis B e antigen (HBeAg) positive mothers with high levels of HBV DNA. Maternal HBV DNA > 6log10 copies/mL (or >200,000 IU/mL) is the major risk for the mother-to-child transmission. Prior observational studies have shown that antiviral therapy including lamivudine or telbivudine use during late pregnancy can safely reduce the rate of vertical transmission in this special population compared to untreated patients.

Tenofovir Disoproxil (TDF), a pregnancy category B medication, reduces HBV DNA and normalizes serum alanine aminotransferase (ALT) in chronic hepatitis B patients (CHB) with few adverse effects. Two aspects on tenofovir use in pregnancy will be evaluated prospectively in this study:

  1. The data on its tolerability and safety in HBeAg+ pregnant women with HBV DNA > 6log10 copies/mL (or > 200,000 IU/mL) during late pregnancy and infants.
  2. Its efficacy in the reduction of HBV vertical transmission rate.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Eligible mothers will be randomized (1:1) to either TDF-treated group or untreated group with about 100 subjects in each arm. The treatment group will receive TDF starting at week 30-32 of gestation until week 4 postpartum; follow up will continue until post-partum week 28 and infants age of 28 weeks. Untreated group will receive the standard of care with similar follow-up schedule as the treatment group.

Study Type

Interventional

Enrollment (Actual)

200

Phase

  • Phase 4

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

  • China
    • Chongqing
      • Chongqing, Chongqing, China, 400038
        • Southwest Hospital
    • Hebei
      • Shijiazhuang, Hebei, China, 050021
        • The Fifth Hospital of Shijiazhuang
    • Henan
      • Nanyang, Henan, China, 473000
        • Nanyang Central Hospital
    • Jiangsu
      • Nanjing, Jiangsu, China, 210003
        • The Second Affiliated Hospital of the Southeast University
    • Jilin
      • Chang Chun, Jilin, China, 130062
        • Hepatobiliary Disease Hospital of Jilin Province

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

20 years to 35 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • documented CHB infection with HBsAg positive > 6 months
  • HBeAg+ CHB pregnant women
  • gestational age between 30-32 weeks
  • HBV DNA > 6 log10 copies/mL (or >200,000 IU/mL)
  • both mother and father of the child are willing to consent for the study

Major Exclusion Criteria:

  • co-infection with hepatitis A, C, D, E, HIV-1 or sexually transmitted disease (STD)
  • decompensated liver disease or significant co-morbidity
  • history of abortion, or diagnosis of fetal defect, or congenital malformation in prior pregnancy
  • antiviral used within six months prior to this pregnancy, or history of renal or tubular function impairment due to adefovir.
  • requirement for other medication during pregnancy to manage other chronic disease(s) or concurrent treatment with immune-modulators, cytotoxic drugs, or steroids
  • the biological father of the child had CHB
  • clinical signs of threatened miscarriage in early pregnancy
  • evidence of hepatocellular carcinoma
  • maternal alanine aminotransferase (ALT) > or = 5 x upper limit of normal (U/mL), or Total Bilirubin > or = 2, or glomerular filtration rate (GFR) < 100, or Albumin < 25 g/L
  • evidence of fetal deformity by ultrasound examination
  • patient is participating other clinical 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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control arm: HBIG & vaccine for infants
Provide standard of care to mothers and standard immunoprophylaxis to their infants
Experimental: TDF treatment arm
tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum for mothers and standard immunoprophylaxis to their infants
Drug: TDF treatment
About 100 mothers treated with tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum, then observed to the end of the study at post-partum week 28, paired infants received standard HBV prophylaxis.
Other Names:
  • Viread, Tenofovir, TDF, Hepatitis B-IgG, Hepatitis B vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Measure the number of infants who have HBV infection at the age of 28 weeks
Time Frame: From the date of birth to age of 28 weeks
From the date of birth to age of 28 weeks
Assessment of the safety and tolerability of TDF, measure the number of participants and paired infants with adverse events
Time Frame: From the date of randomization until 28 weeks of postpartum.
From the date of randomization until 28 weeks of postpartum.

Secondary Outcome Measures

Outcome Measure
Time Frame
Measure maternal HBV DNA reduction during the study period when compared to the baseline
Time Frame: From the date of radomization to the time of delivery (upto 12 weeks from the radomization)
From the date of radomization to the time of delivery (upto 12 weeks from the radomization)
Measure maternal HBV DNA reduction during the study period when compared to the baseline
Time Frame: From the date of radomization to the time of delivery (about 8 - 10 weeks from the radomization)
From the date of radomization to the time of delivery (about 8 - 10 weeks from the radomization)
percentage of mothers with sero-negativity or sero-conversion of HBsAg and/or HBeAg in each group for comparison
Time Frame: From the date of randomization until 28 weeks of postpartum.
From the date of randomization until 28 weeks of postpartum.

Collaborators and Investigators

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

Sponsor

New Discovery LLC

Collaborators

Gilead Sciences

Investigators

  • Study Chair: Calvin Q Pan, MD, Leading Principle Investigator, Division of Gastroenterology and Hepatology, NYU Langone Medical Center, New York
  • Study Director: Zhongping Duan, MD, Capital Medical University
  • Principal Investigator: Shuqin Zhang, MD, Hepatobiliary Disease Hospital of Jilin Province, Jilin, China
  • Principal Investigator: Erhei Dai, MD, The Fifth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China
  • Principal Investigator: Guorong Han, MD, The Second Affiliated Hospital of the Southeast University, Nanjing, China
  • Principal Investigator: Huaihong Zhang, MD, Nanyang Central Hospital, Nanyang, Henan, China
  • Principal Investigator: Yuming Wang, MD, Southwest Hospital, Chongqing, Chongqing, China

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)

March 1, 2012

Primary Completion (Actual)

April 28, 2014

Study Completion (Actual)

June 28, 2018

Study Registration Dates

First Submitted

November 30, 2011

First Submitted That Met QC Criteria

December 6, 2011

First Posted (Estimate)

December 8, 2011

Study Record Updates

Last Update Posted (Actual)

December 9, 2019

Last Update Submitted That Met QC Criteria

December 6, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IN-US 174-0174

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.

Clinical Trials on Viremia

Clinical Trials on TDF treatment

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Slovakia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe