Safety and Efficacy of TAF to Prevent MTCT of HBV in Middle/Late Pregnancies With High HBV DNA Load

Pregnancy Related Clinical Trial

Official title:

Safety and Efficacy of Tenofovir Alafenamide to Prevent Mother-to-child Transmission of Hepatitis B Virus in Middle/Late Pregnancies With High Hepatitis B Virus DNA Load: A Prospective Multicenter Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05466071
• Other study ID #: LCYJ-2021-005
• Status: Recruiting
• Start date: July 1, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: December 2023
• Source: The Third Affiliated Hospital of Guangzhou Medical University
• Contact: Bing Situ, Master
• Phone: +86 20 81292050
• Email: lilyst[@]126.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Mother-to-child transmission (MTCT) is still the main transmission route of HBV in high-endemic areas, such as China, sub-Saharan Africa, etc. Some infants born of mothers with high HBV DNA load (≥2×10^5 IU/ml) are still infected with HBV even if these infants receive the combined immunization on time. Therefore, guidelines including AASLD and EASL recommend that pregnant women with high HBV DNA load should take antiviral drugs (tenofovir disoproxil fumarate or telbivudine) to reduce MTCT of HBV from gestation 24-28 weeks.

However, side effects of TDF on infants are reported. For example, neutropenia and the decrease of bone mineral density are found in early age infants who are ever exposed to TDF during their fetal life.

Tenofovir alafenamide (TAF), a new prodrug of tenofovir (TFV), has a higher antiviral potency, a higher peripheral blood mononuclear cell (PBMC) intracellular tenofovir diphosphate (TFV pp) level and a lower plasma TFV concentration. As the successor of TDF, the dose of TAF that is took orally every day is approximately 1/10 of TDF. TAF has a much lower risk of kidney toxicity and has almost no effect on the bone mineral density. TAF has been approved and recommended as the first-line drug to treat patients with chronic hepatitis B (CHB) by AASLD, EASL, etc. However, there are relatively few data of TAF on pregnancies with high HBV DNA load. It is urgently to clarify the safety and efficacy of TAF on interrupting MTCT of HBV in pregnancies with high HBV DNA load.

In the present study, the investigators enroll middle/late pregnancies with high HBV DNA load(≥2×10^5 IU/ml). The participants are randomly divided into two groups. Then the participants are treated with TAF or TDF respectively. All enrolled participants are followed-up for 2 years. Objectives of the present study are as follows:

A. To clarify safety and efficacy of TAF on interrupting MTCT of HBV in middle/late pregnancies with high HBV DNA load.

B. To clarify effects of TAF on obstetric complications in middle/late pregnancies with CHB.

C. To clarify effects of TAF on birth defects of infants born in mothers with CHB.

D. To clarify the change of virology and biochemistry indexes in women with CHB during pregnancy and postpartum.

E. To clarify effects of TAF treatment on participants. F. To clarify growth parameters of the infants exposed to TAF during their fetal life.

G. To clarify the pharmacokinetics of TAF in pregnant populations.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

Inclusion Criteria:

• Age of 20-40 years.

• Positive for HBsAg =6 months.

• HBV DNA load of = 2×10^5 IU/ml.

• Gestation 24-28 weeks .

• Pregnancies are orally administrated with TAF (25mg/day) or TDF (300mg/day) from 24-28 weeks of gestation.

• The good compliance of patients.

Exclusion Criteria:

• Patients with antibodies against HIV, HCV, HDV, or other forms of chronic liver disease.

• Evidence of hepatocellular carcinoma, decompensated liver disease, auto-immune hepatitis, or significant renal, cardiovascular, respiratory or neurological comorbidity.

• Concurrent treatment with nephrotoxic drugs, glucocorticoids, cytotoxic drugs, nonsteroidal anti-inflammatory drugs, or immune modulators.

• Ultra-sonographic evidence of fetal deformity, abnormal fetal development or placental abnormality.

• Clinical signs of threatened miscarriage.

• History of complication of pregnancy.

• History of nucleoside analogues (NA) treatment.

Related Conditions & MeSH terms

• Chronic Hepatitis b
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Pregnancy Related

Locations

Country	Name	City	State
China	The Third Affiliated Hospital, Guangzhou Medical University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Xingfei Pan

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of interrupting MTCT	The proportion of HBV infection in the infants at 1 year of age.; Testing for HBsAg in the infants between 7 and 12 months of age.	During 7-12 months after birth
Primary	HBV DNA load in pregnancies	HBV DNA load is measured during 24-28 weeks of gestation and at birth, respectively.	After enrollment and up to delivery
Primary	ALT levels in pregnancies	ALT levels are measured every month during pregnancy.	After enrollment and up to delivery
Primary	HBeAg conversion rate in pregnancies	HBeAg is measured every 6 months during pregnancy.	After enrollment and up to delivery
Secondary	Mode of delivery.	Recording the mode of delivery (vaginal delivery or cesarean delivery), and what kind of anesthesia (general anesthesia or combined spinal/epidural anesthesia) is used in the cesarean delivery.	At the time of delivery
Secondary	The proportion of birth defects in the infants at 1 month age.	Measuring which kinds of congenital abnormality the infants have.	Up to 1 month after birth
Secondary	Head circumferences of infants	Head circumferences of infants are measured and analyzed.	Once a year up to 3 years old after birth
Secondary	Weights of infants	Weights of infants are measured and analyzed.	Once a year up to 3 years after birth
Secondary	Heights of the infants	Heights of the infants are measured and analyzed.	Once a year up to 3 years after birth
Secondary	Denver Developmental Screening Test of infants	Denver Developmental Screening Test of infants is measured and analyzed.	Once a year up to 3 years after birth
Secondary	HBV DNA load in postpartum mothers	HBV DNA load is measured every 6 months postpartum.	Up to 2 years after delivery
Secondary	ALT levels in postpartum mothers	ALT levels are measured every month during the first 3 months postpartum and every 6 months from the fourth month postpartum.	Up to 2 years after delivery
Secondary	HBeAg conversion rate in postpartum mothers	HBeAg is measured every 6 months after delivery.	Up to 2 years after delivery
Secondary	Liver function of women with CHB	Liver function is measured every 6 months postpartum.	Up to 2 years after delivery
Secondary	Liver ultrasound test of women with CHB	Liver ultrasound is performed every 6 months postpartum.	Up to 2 years after delivery
Secondary	The blood drug concentration of TAF in pregnancies	After the administration of TAF to pregnant women, 4 ml of upper extremity venous drug-containing blood is collected between 30 and 60 minutes before the next taking TAF at the 5th, 12th, 19th, 26th, 33rd, and 40th days, respectively. After a series of laboratory processes, the supernatant is taken for HPLC-MS/MS analysis, and the blood drug concentration at each time point is calculated according to the standard curve.	Day 5 up to day 40 after the administration of TAF