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

Sponsor
Johns Hopkins Bloomberg School of Public Health (Other)
Overall Status
Unknown status
CT.gov ID
NCT02995005
Collaborator
Thrasher Research Fund (Other), Shoklo Malaria Research Unit (Other), Chiang Mai University (Other), University of Oxford (Other)
170
Enrollment
1
Location
1
Arm
19.3
Anticipated Duration (Months)
8.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Tenofovir Disoproxil Fumarate
 Phase 1/Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
170 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
Single group study.Single group study.
Masking:
None (Open Label)
Masking Description:
No masking, just one interventional group.
Primary Purpose:
Prevention
Official Title:
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
Actual Study Start Date :
May 24, 2018
Anticipated Primary Completion Date :
Jul 31, 2019
Anticipated Study Completion Date :
Dec 31, 2019

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. The time (from inclusion through delivery; up to 6 months) to HBV DNA suppression (<100 IU/ml) [Every month]

      HBV DNA will be monitored every month

    2. The proportion of women with undetectable HBV DNA at delivery [At delivery]

      HBV DNA will be monitored at delivery.

    Secondary Outcome Measures

    1. Proportion of hepatitis B flares in mothers postpartum [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.

    2. 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) [Every month]

      All women will be surveyed at monthly visits and at birth to measure adherence including actionable barriers.

    3. 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) [Every month]

      Drug accountability using standard methods (subtracting the number of tablets left from the number of tablets distributed).

    4. 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) [Every month]

      Measurement of tenofovir drug levels

    5. The proportion of hepatitis B infections in the offspring at 1 year of age [Between month 2 and 12 month]

      Testing for HBsAg in children between 2 and 12 months of age.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    16 Years to 49 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Shoklo Malaria Research Unit Mae Sot Thailand

    Sponsors and Collaborators

    • Johns Hopkins Bloomberg School of Public Health
    • Thrasher Research Fund
    • Shoklo Malaria Research Unit
    • Chiang Mai University
    • University of Oxford

    Investigators

    • Principal Investigator: Stephan Ehrhardt, MD, Johns Hopkins Bloomberg School of Public Health

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Johns Hopkins Bloomberg School of Public Health
    ClinicalTrials.gov Identifier:
    NCT02995005
    Other Study ID Numbers:
    • JHSPH-TDF
    • NCT03167229
    First Posted:
    Dec 16, 2016
    Last Update Posted:
    Aug 10, 2018
    Last Verified:
    Apr 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    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
    Keywords provided by Johns Hopkins Bloomberg School of Public Health
    mother to child transmission
    hepatitis B
    tenofovir
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis B
    Hepatitis
    Tenofovir

    Study Results

    No Results Posted as of Aug 10, 2018