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

New Discovery

Status and phase: Completed; Phase 4

Conditions: Viremia; Hepatitis B Infection; Chronic Infection

Treatments: Drug: TDF treatment

Study type: Interventional

Funder types: Industry

Identifiers

NCT01488526

IN-US 174-0174

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 patients

Sex: Female

Ages: 20 to 35 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

Control arm: HBIG & vaccine for infants

No Intervention group

Description:

Provide standard of care to mothers and standard immunoprophylaxis to their infants

TDF treatment arm

Experimental group

Description:

tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum for mothers and standard immunoprophylaxis to their infants

Treatment:

Drug: TDF treatment