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Study of Tenofovir Alafenamide in HBV-Infected Pregnant Women

Phase 4
Recruiting
Conditions
Chronic Hepatitis b
Tenofovir Alafenamide Fumarate
Interventions
Registration Number
NCT05853718
Lead Sponsor
First People's Hospital of Hangzhou
Brief Summary

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

Detailed Description

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
50
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TAF antiviral therapy groupTenofovir Alafenamide TabletsEligible hepatitis B pregnant women are given TAF antiviral therapy (25mg, oral, 1/day) from week 28-32 of gestation until delivery
Primary Outcome Measures
NameTimeMethod
Rate of mother-to-child transmission of HBVDuring 7-12 months after birth

Testing for HBsAg in the infants between 7 and 12 months of age.

Assessment on the pharmacokinetics of TAF and TFV in plasma of pregnant womenThe day before delivery

When taking the last TAF before delivery , 2ml of drug-containing blood was collected from the upper extremity veins at 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24h after taking TAF. Blood drug concentration at each time point was calculated according to standard curve.

Rate of birth defect of infantsFrom the date of birth to age of 28 weeks

The proportion of infants with the aforementioned abnormalities discovered during the study period

Secondary Outcome Measures
NameTimeMethod
Drug concentration of TAF and TFV in breast milk after drug withdrawalImmediately after breast milk is available and last for 5 days

Postpartum breast milk was collected to measure TAF and TFV concentrations after drug withdrawal

Concentrations of TAF and TFV in infant urine and plantar bloodWithin 72 hours of birth

Collect infant urine and plantar blood within 72 hours of birth

Reduction of HBV DNA levels at deliveryAt delivery

Reduction of HBV DNA levels (IU/mL) at delivery when compared to the baseline before initiating TAF

Trial Locations

Locations (1)

Hangzhou First People's Hospital

🇨🇳

Hangzhou, Zhejiang, China

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