Study of Tenofovir Alafenamide in HBV-Infected Pregnant Women

Study to Evaluate the Pharmacokinetic, Safety, and Efficacy of TAF in HBV-Infected Pregnant Women

The purpose of this study is to evaluate the pharmacokinetics, efficacy and safety of TAF in HBV-infected pregnant women.

Pregnant women with high viral load (HBV DNA>2 × 10^5 IU/mL ) are recommended to be given Tenofovir Disoproxil Fumarate(TDF) for mother-to-child blocking of Chronic hepatitis B(CHB) by guidelines. Tenofovir alafenamide (TAF) is a new targeted pro-drug of Tenofovir (TFV) and was approved for use in China in December 2018. Compared with TDF, the therapeutic dose of TAF is small. 25mg TAF can obtain the antiviral effect similar to 300mg TDF, thus reducing the concentration of TFV in the blood.

This is a prospective clinical study, aiming to evaluate the pharmacokinetics, efficacy and safety of TAF in HBV-infected pregnant women when used for prevention of mother-to-child transmission of hepatitis B virus. 50 HBeAg-positive and HBV DNA levels ≥ 2 × 10^5 IU/mL pregnant women will be enrolled to receive Tenofovir alafenamide (TAF) from week 28-32 of gestation until delivery. According to the mother's wishes, intensive blood samples will be collected to determine the concentration of TAF and TFV in plasma of pregnant women before and after taking TAF, calculate the pharmacokinetic parameters. And the mother's milk is collected every day for 5 days for TAF concentration determination. The primary endpoint was the pharmacokinetic parameters of TAF and TFV, rate of mother-to-child transmission, the congenital malformation rate of infants. The secondary endpoint was the decrease of HBV DNA level at delivery, the clearance and seroconversion rate of HBeAg, postpartum ALT flare, concentration of TAF and TFV in milk,and other adverse events of mothers and infants.

Inclusion Criteria:

• Age of 20-40 years; Positive for hepatitis B surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg); HBV DNA level >200 000 IU/mL during the 24th-32nd week of pregnancy; Willing to take TAF for mother-to-child blockade; Both husband and wife are willingly sign an informed consent.

Exclusion Criteria:

• Co-infected with hepatitis C or HIV, or other chronic diseases; History of spontaneous abortion or congenital malformation; Decompensated cirrhosis and liver cancer; History of kidney injury, CCr <50ml/min and urine protein test positive (>300mg/L); Fetal malformations detected by B-ultrasound during pregnancy; ALT > 2×upper limit of normal (ULN); TBIL ≥ 1×ULN; Albumin (ALB) < 25 g/L.