Clinical trial NCT05853718: Study of Tenofovir Alafenamide in HBV-Infected Pregnant Women
Official title: Study to Evaluate the Pharmacokinetic, Safety, and Efficacy of TAF in HBV-Infected Pregnant Women
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Hepatitis b
Tenofovir Alafenamide Fumarate
Keywords: pharmacokinetics
CHB
TAF
pregnancy
mother-to-child transmission
Lead sponsor: First People's Hospital of Hangzhou
Sponsor class: OTHER
First posted: 2023-05-11
Enrollment: 50
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Assessment on the pharmacokinetics of TAF and TFV in plasma of pregnant women
timeFrame: The day before delivery
measure: Rate of mother-to-child transmission of HBV
timeFrame: During 7-12 months after birth
measure: Rate of birth defect of infants
timeFrame: From the date of birth to age of 28 weeks
Secondary outcomes:
measure: Reduction of HBV DNA levels at delivery
timeFrame: At delivery
measure: Drug concentration of TAF and TFV in breast milk after drug withdrawal
timeFrame: Immediately after breast milk is available and last for 5 days
measure: Concentrations of TAF and TFV in infant urine and plantar blood
timeFrame: Within 72 hours of birth
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Hangzhou First People's Hospital
state: Zhejiang
Study officials:
affiliation: First People's Hospital of Hangzhou
name: Zhiyuan Ma, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: First People's Hospital of Hangzhou
name: Siying Li, MD
role: PRINCIPAL_INVESTIGATOR
References: