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

NCT02995005 | Completed Phase 1

• 1 other identifier: JHSPH-TDF
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis B

Keywords

mother to child transmission; hepatitis B; tenofovir

Outcome Measures

Primary Outcomes (2)

• The time (from inclusion through delivery; up to 6 months) to HBV DNA suppression (<100 IU/ml)

  HBV DNA will be monitored every month

  Up to 9 months

• The proportion of women with undetectable HBV DNA at delivery

  HBV DNA will be monitored at delivery.

  At delivery

Secondary Outcomes (5)

• Proportion of hepatitis B flares in mothers postpartum

  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)

  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)

  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)

  Up to 9 months

• The proportion of hepatitis B infections in the offspring at 1 year of age

  Between month 2 and 12 month

Study Arms (1)

Tenofovir Disoproxil Fumarate

EXPERIMENTAL

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

Interventions

Tenofovir Disoproxil Fumarate DRUG

300 mg daily

Also known as: Viread

Tenofovir Disoproxil Fumarate

Eligibility Criteria

• Age: 16 Years - 49 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Shoklo Malaria Research Unit

Mae Sot, Thailand

Location

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MeSH Terms

Conditions

Hepatitis B

Interventions

Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Stephan Ehrhardt, MD

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: No masking, just one interventional group.
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single group study.

Study Record Dates

• First Submitted: December 8, 2016
• First Posted: December 16, 2016
• Study Start: May 24, 2018
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: February 6, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will become available 6 months after publication of the main report.
• Access Criteria: Permission by corresponding author

Locations

TH (1)