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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Hepatitis b; Tenofovir Alafenamide Fumarate
• Intervention / Treatment: Drug: Tenofovir Alafenamide Tablets

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 Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jie Jin, MD; Phone Number: 86 13372517879; Email: jinjie0429@163.com
• Study Contact Backup: Name: Zhiyuan Ma, PhD; Phone Number: 86 18858273870; Email: zhiyuan_ma@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Hangzhou First People's Hospital
      • Contact: Jie Jin, MD; Phone Number: 86 13372517879; Email: jinjie0429@163.com
      • Principal Investigator: Zhiyuan Ma, PhD
      • Principal Investigator: Siying Li, MD
      • Sub-Investigator: Yi Jiang, MD
      • Sub-Investigator: Jinfeng Shi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment on the pharmacokinetics of TAF and TFV in plasma of pregnant women	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.	The day before delivery
Rate of mother-to-child transmission of HBV	Testing for HBsAg in the infants between 7 and 12 months of age.	During 7-12 months after birth
Rate of birth defect of infants	The proportion of infants with the aforementioned abnormalities discovered during the study period	From the date of birth to age of 28 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of HBV DNA levels at delivery	Reduction of HBV DNA levels (IU/mL) at delivery when compared to the baseline before initiating TAF	At delivery
Drug concentration of TAF and TFV in breast milk after drug withdrawal	Postpartum breast milk was collected to measure TAF and TFV concentrations after drug withdrawal	Immediately after breast milk is available and last for 5 days
Concentrations of TAF and TFV in infant urine and plantar blood	Collect infant urine and plantar blood within 72 hours of birth	Within 72 hours of birth

Collaborators and Investigators

• Sponsor: First People's Hospital of Hangzhou
• Investigators: Principal Investigator: Zhiyuan Ma, PhD, First People's Hospital of Hangzhou; Principal Investigator: Siying Li, MD, First People's Hospital of Hangzhou

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2021
• Primary Completion (Anticipated): July 30, 2024
• Study Completion (Anticipated): December 30, 2024

Study Registration Dates

• First Submitted: April 26, 2023
• First Submitted That Met QC Criteria: May 8, 2023
• First Posted (Estimate): May 11, 2023

Study Record Updates

• Last Update Posted (Estimate): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: pharmacokinetics; pregnancy; CHB; mother-to-child transmission; TAF
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: IIT-20210825-0020-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes