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Study of Tenofovir Alafenamide in HBV-Infected Pregnant Women

Primary Purpose

Chronic Hepatitis b, Tenofovir Alafenamide Fumarate

Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Tenofovir Alafenamide Tablets
Sponsored by
First People's Hospital of Hangzhou
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis b focused on measuring pharmacokinetics, CHB, TAF, pregnancy, mother-to-child transmission

Eligibility Criteria

20 Years - 40 Years (Adult)FemaleDoes not accept 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.

Sites / Locations

  • Hangzhou First People's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TAF antiviral therapy group

Arm Description

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

Outcomes

Primary Outcome Measures

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.
Rate of mother-to-child transmission of HBV
Testing for HBsAg in the infants between 7 and 12 months of age.
Rate of birth defect of infants
The proportion of infants with the aforementioned abnormalities discovered during the study period

Secondary Outcome Measures

Reduction of HBV DNA levels 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
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
Collect infant urine and plantar blood within 72 hours of birth

Full Information

First Posted
April 26, 2023
Last Updated
May 8, 2023
Sponsor
First People's Hospital of Hangzhou
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1. Study Identification

Unique Protocol Identification Number
NCT05853718
Brief Title
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 6, 2021 (Actual)
Primary Completion Date
July 30, 2024 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
First People's Hospital of Hangzhou

4. Oversight

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

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis b, Tenofovir Alafenamide Fumarate
Keywords
pharmacokinetics, CHB, TAF, pregnancy, mother-to-child transmission

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TAF antiviral therapy group
Arm Type
Experimental
Arm Description
Eligible hepatitis B pregnant women are given TAF antiviral therapy (25mg, oral, 1/day) from week 28-32 of gestation until delivery
Intervention Type
Drug
Intervention Name(s)
Tenofovir Alafenamide Tablets
Other Intervention Name(s)
TAF
Intervention Description
Take 25mg TAF daily from week 28-32 of gestation until delivery
Primary Outcome Measure Information:
Title
Assessment on the pharmacokinetics of TAF and TFV in plasma of pregnant women
Description
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.
Time Frame
The day before delivery
Title
Rate of mother-to-child transmission of HBV
Description
Testing for HBsAg in the infants between 7 and 12 months of age.
Time Frame
During 7-12 months after birth
Title
Rate of birth defect of infants
Description
The proportion of infants with the aforementioned abnormalities discovered during the study period
Time Frame
From the date of birth to age of 28 weeks
Secondary Outcome Measure Information:
Title
Reduction of HBV DNA levels at delivery
Description
Reduction of HBV DNA levels (IU/mL) at delivery when compared to the baseline before initiating TAF
Time Frame
At delivery
Title
Drug concentration of TAF and TFV in breast milk after drug withdrawal
Description
Postpartum breast milk was collected to measure TAF and TFV concentrations after drug withdrawal
Time Frame
Immediately after breast milk is available and last for 5 days
Title
Concentrations of TAF and TFV in infant urine and plantar blood
Description
Collect infant urine and plantar blood within 72 hours of birth
Time Frame
Within 72 hours of birth

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Pregnant woman is eligible for this study.
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jie Jin, MD
Phone
13372517879
Ext
86
Email
jinjie0429@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Zhiyuan Ma, PhD
Phone
18858273870
Ext
86
Email
zhiyuan_ma@zju.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhiyuan Ma, PhD
Organizational Affiliation
First People's Hospital of Hangzhou
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Siying Li, MD
Organizational Affiliation
First People's Hospital of Hangzhou
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hangzhou First People's Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie Jin, MD
Phone
13372517879
Ext
86
Email
jinjie0429@163.com
First Name & Middle Initial & Last Name & Degree
Zhiyuan Ma, PhD
First Name & Middle Initial & Last Name & Degree
Siying Li, MD
First Name & Middle Initial & Last Name & Degree
Yi Jiang, MD
First Name & Middle Initial & Last Name & Degree
Jinfeng Shi, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of Tenofovir Alafenamide in HBV-Infected Pregnant Women

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