Clinical trial NCT05466071: Safety and Efficacy of TAF to Prevent MTCT of HBV in Middle/Late Pregnancies With High HBV DNA Load
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Hepatitis b
Pregnancy Related
Keywords: Tenofovir Alafenamide
Safety and Efficacy
Mother-to-Child Transmission
High HBV DNA Load
Lead sponsor: The Third Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
First posted: 2022-07-20
Enrollment: 200
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: We enroll Child-bearing age women with chronic HBV infection, who already become middle/late pregnancy, and visit in 3 hospitals (The Third Affiliated Hospital of Guangzhou Medical University, People's Hospital of Guangzhou Huadu District and He Xian Memorial Hospital of Guangzhou Panyu District).

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: The proportion of interrupting MTCT
timeFrame: During 7-12 months after birth
measure: HBV DNA load in pregnancies
timeFrame: After enrollment and up to delivery
measure: ALT levels in pregnancies
timeFrame: After enrollment and up to delivery
measure: HBeAg conversion rate in pregnancies
timeFrame: After enrollment and up to delivery
Secondary outcomes:
measure: Mode of delivery.
timeFrame: At the time of delivery
measure: The proportion of birth defects in the infants at 1 month age.
timeFrame: Up to 1 month after birth
measure: Head circumferences of infants
timeFrame: Once a year up to 3 years old after birth
measure: Weights of infants
timeFrame: Once a year up to 3 years after birth
measure: Heights of the infants
timeFrame: Once a year up to 3 years after birth
measure: Denver Developmental Screening Test of infants
timeFrame: Once a year up to 3 years after birth
measure: HBV DNA load in postpartum mothers
timeFrame: Up to 2 years after delivery
measure: ALT levels in postpartum mothers
timeFrame: Up to 2 years after delivery
measure: HBeAg conversion rate in postpartum mothers
timeFrame: Up to 2 years after delivery
measure: Liver function of women with CHB
timeFrame: Up to 2 years after delivery
measure: Liver ultrasound test of women with CHB
timeFrame: Up to 2 years after delivery
measure: The blood drug concentration of TAF in pregnancies
timeFrame: Day 5 up to day 40 after the administration of TAF
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Third Affiliated Hospital, Guangzhou Medical University
state: Guangdong
Study officials:
References: