Antiviral Prophylaxis and Infant Vaccination to Prevent Perinatal Hepatitis B Infection

Study Overview
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Brief Summary
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Most new hepatitis B virus (HBV) infections are acquired perinatally. In this study, pregnant women with HBsAg and HBeAg will receive tenofovir disoproxil fumarate during the last trimester of pregnancy and for two months following delivery. Their infants will receive hepatitis B (HB) immunization, starting with a first dose soon after birth. We hypothesize that the risk of mother-to-child transmission of HBV will be lower than 2%. The results of the study will help define policy to manage HBV infected pregnant women to prevent perinatal transmission.

Detailed Description
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This is a prospective multi-center, multi-country (Thailand and Lao PDR), open-label, single arm clinical trial in HBsAg and HBeAg positive pregnant women (from 28 weeks until one year postpartum) and their infants (until 18 months of age). Pregnant women with HBsAg and HBeAg will receive tenofovir disoproxil fumarate 300 mg once daily from 28 weeks of pregnancy until two months postpartum. Their infants will receive hepatitis B (HB) immunization, starting with the first dose soon after birth. The study aims to show that substituting maternal antiviral treatment for infant HBIg can be favorably considered in settings where HBIg plus vaccine has been used as well as in settings where only vaccine is used. A significant improvement over the standard HBIg + vaccine strategy would be that adding an antiviral strategy results in less than 2% transmission. A total of 499 women and their infants will be enrolled in public hospitals in Thailand and Lao PDR. The study will be monitored by a Data and Safety Monitoring Board (DSMB) at least annually.

Official Title
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A Maternal Short Course of Tenofovir Disoproxil Fumarate and Infant Vaccine to Prevent Mother-to-child Transmission of Hepatitis B Virus

Conditions
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Hepatitis B, Pregnancy

Intervention / Treatment
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* Drug: Anti-HBV antiviral prophylaxis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnancy Age ≥18 years Negative HIV antibody test during current pregnancy Positive HBsAg test during current pregnancy Positive HBeAg using a rapid test during current pregnancy Absence of clinical symptoms of liver disease Gestational age of 28 weeks (+/- 7 days) based on the obstetrician judgment guided by the review of the date of last menstruation period. Willing and able to provide written informed consent Agreeing to bring her infants(s) at the planned study visits at one of the study site until the last visit (18 months after birth) and to inform the site investigators if plans to move to another place and not be able to return to the clinic Understand the need for adequate infant immunization for her infant(s) and accept that blood draws will be performed to determine the infant HBV infection status Exclusion Criteria: Receipt of anti-HBV antivirals at any time during the last 9 months Known liver cirrhosis or evidence of hepatocellular carcinoma Creatinine clearance <50 ml/min, calculated using the Cockcroft-Gault formula Confirmed dipstick proteinuria >1+ (>30 mg/dL) or normoglycemic glycosuria Evidence of pre-existing fetal anomalies incompatible with life Any concomitant condition or treatment that, in the view of the clinical site investigator, would contraindicate participation or compromise adherence to treatment and satisfactory follow up in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: All participants receive the intervention
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Anti-HBV antiviral prophylaxis|Tenofovir disoproxil fumarate (TDF), one 300 mg tablet once a day from 28 weeks' gestation through two months postpartum|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infant hepatitis B infection status | HBsAg positive confirmed by PCR detection of HBV DNA. | Six months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal HBV DNA changes | Description of the effect of tenofovir disoproxil fumarate on maternal HBV DNA levels | From enrollment until end of study treatment scheduled 2 months after delivery | 
| Infant levels of anti-HBs antibodies | Levels of anti-HBs antibodies in infants in the absence of HBIg administration at birth | At 1, 2, 4, 6, and 12 months of age | 
| HBV infection status in all infants regardless of maternal response to study treatment | HBsAg positive confirmed by PCR detection of HBV DNA in all infants, i.e. including those born to women with unsatisfactory virological response to study treatment | At 6 months of age | 
| Serious adverse events | Occurrence of maternal serious adverse events (ICH SAEs) including DAIDS grade 4 signs and symptoms regardless of their relatedness to the study treatment | From enrollment until 12 months postpartum | 
| Serious adverse events | Occurrence of infant serious adverse events (ICH SAEs) including DAIDS grade 4 signs and symptoms regardless of their relatedness to the study treatment | From birth until 12 months of age | 
| Preterm live births | Proportion of neonates born alive before 37 weeks of pregnancy | Delivery | 
| Low birth weight | Proportion of neonates born alive with birth weight of 2,499 g or less, regardless of gestational age | Delivery | 
| Active or previous transient infection in children | Detection of anti-HBc antibodies among all infants | At 18 months of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B, Hepatitis B eAg, Pregnancy