Study of Tenofovir Alafenamide in HBV-Infected Pregnant Women

Sponsor

First People's Hospital of Hangzhou (Other)

Overall Status

Recruiting

CT.gov ID

NCT05853718

Collaborator

(none)

Enrollment

Location

Arm

43.8

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis b Tenofovir Alafenamide Fumarate	Drug: Tenofovir Alafenamide Tablets	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 6, 2021

Anticipated Primary Completion Date :

Jul 30, 2024

Anticipated Study Completion Date :

Dec 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAF antiviral therapy group Eligible hepatitis B pregnant women are given TAF antiviral therapy (25mg, oral, 1/day) from week 28-32 of gestation until delivery	Drug: Tenofovir Alafenamide Tablets Take 25mg TAF daily from week 28-32 of gestation until delivery Other Names: TAF

Arm

Intervention/Treatment

Experimental: TAF antiviral therapy group

Eligible hepatitis B pregnant women are given TAF antiviral therapy (25mg, oral, 1/day) from week 28-32 of gestation until delivery

Drug: Tenofovir Alafenamide Tablets

Take 25mg TAF daily from week 28-32 of gestation until delivery

Other Names:

TAF

Outcome Measures

Primary Outcome Measures

Assessment on the pharmacokinetics of TAF and TFV in plasma of pregnant women [The 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 mother-to-child transmission of HBV [During 7-12 months after birth]
Testing for HBsAg in the infants between 7 and 12 months of age.
Rate of birth defect of infants [From 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

Reduction of HBV DNA levels at delivery [At delivery]
Reduction of HBV DNA levels (IU/mL) at delivery when compared to the baseline before initiating TAF
Drug concentration of TAF and TFV in breast milk after drug withdrawal [Immediately 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 blood [Within 72 hours of birth]
Collect infant urine and plantar blood within 72 hours of birth

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.