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

NCT05466071 | Unknown

• 1 other identifier: LCYJ-2021-005
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Hepatitis b; Pregnancy Related

Keywords

Tenofovir Alafenamide; Safety and Efficacy; Mother-to-Child Transmission; High HBV DNA Load

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• ALT levels in pregnancies

  ALT levels are measured every month during pregnancy.

  After enrollment and up to delivery

• HBeAg conversion rate in pregnancies

  HBeAg is measured every 6 months during pregnancy.

  After enrollment and up to delivery

Secondary Outcomes (12)

• Mode of delivery.

  At the time of delivery

• The proportion of birth defects in the infants at 1 month age.

  Up to 1 month after birth

• Head circumferences of infants

  Once a year up to 3 years old after birth

• Weights of infants

  Once a year up to 3 years after birth

• Heights of the infants

  Once a year up to 3 years after birth

Study Arms (2)

TAF group

Patients who take TAF during pregnancy.

TDF group

Patients who take TDF during pregnancy.

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• 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).

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xingfei Pan: lead

Study Sites (1)

The Third Affiliated Hospital, Guangzhou Medical University

Guangzhou, Guangdong, 510150, China

RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Bing Situ, Master

CONTACT

+86 20 81292050; lilyst@126.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Department of Infectious Diseases

Study Record Dates

• First Submitted: July 7, 2022
• First Posted: July 20, 2022
• Study Start: July 1, 2021
• Primary Completion: June 30, 2024
• Study Completion: December 31, 2024
• Last Updated: December 29, 2023

Record last verified: 2023-12

Locations

CN (1)