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

JHSPH-TDF

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.

2018-05-24

2023-01-31

2023-01-31

Completed

Early phase I

98

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Single group study.', 'primaryPurpose': 'PREVENTION', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'No masking, just one interventional group.'}}, 'enrollmentInfo': {'count': 98, 'type': 'ACTUAL'}}

2023-02-06