Tenofovir Alafenamide to Prevent Perinatal Transmission of Hepatitis B

NCT ID: NCT04850950

Last Updated: 2021-04-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-26
• Study Completion Date: 2022-12-31

Brief Summary

To investigate the safety and efficacy of tenofovir alafenamide (orally 25 mg per day) treated in inactive chronic hepatitis B virus (HBV)-infected pregnant women with high viral load from the late pregnancy until the delivery date or postpartum 1 month.

Detailed Description

The investigators intend to include 240 inactive chronic hepatitis B virus (HBV)-infected pregnant women who have an HBV DNA level higher than 200,000 IU per milliliter. Participants will be randomly assigned, in a 1:1 ratio, to receive tenofovir alafenamide (orally 25 mg per day) from the late pregnancy until the delivery date or postpartum 1 month. All the infants will receive standard immunoprophylaxis (100 IU of hepatitis B immunoglobulin and 10 μg of hepatitis B vaccine within 12 hours of birth; the second injection of 10 μg of HBV vaccine will inject at 1 month; and the third dose of 10 μg of HBV vaccine will give at 6 months). The pregnant women and their infants will be followed until postpartum month 7. The primary outcomes are the birth defects and rates of perinatal transmission of HBV. During the prenatal period or the postnatal period up to 7 months of age, cases of a structural defect in newborns or infants were reported as birth defects. The rate of perinatal transmission was defined as the proportion of infants who are positive for hepatitis B surface antigen at 7 months of age. The secondary safety outcomes are the occurrence of maternal or infant adverse events during the study period. Maternal safety evaluations mainly include any adverse events and complications, hepatitis B virologic breakthrough, alanine aminotransferase flare, and so on. Infant' safety profiles mainly included Apgar scores at 1 minute, any abnormal conditions during the study period, and anthropometric indexes at birth and 7 months of age. The secondary efficacy outcomes are the percentages of mothers with an HBV DNA level of less than 200,000 IU per milliliter just before or at delivery, and the hepatitis B e antigen and surface antigen loss or seroconversion in mothers at postpartum month 7.

Conditions

Chronic Hepatitis B; Mother-to-Child Transmission; Safety; Efficacy; Hepatitis B Virus; Tenofovir Alafenamide Fumarate

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Arm 1

Tenofovir alafenamide fumarate discontinued at delivery date.

Group Type: EXPERIMENTAL

Tenofovir Alafenamide fumarate 25mg Oral Tablet

Intervention Type: DRUG

Tenofovir alafenamide fumarate initiated from the late pregnancy to the delivery date or postpartum month 1.

Arm 2

Tenofovir alafenamide fumarate discontinued at postpartum month 1.

Group Type: EXPERIMENTAL

Tenofovir Alafenamide fumarate 25mg Oral Tablet

Intervention Type: DRUG

Tenofovir alafenamide fumarate initiated from the late pregnancy to the delivery date or postpartum month 1.

Interventions

Tenofovir Alafenamide fumarate 25mg Oral Tablet

Tenofovir alafenamide fumarate initiated from the late pregnancy to the delivery date or postpartum month 1.

Intervention Type: DRUG

Other Intervention Names

VEMLIDY®

Eligibility Criteria

Inclusion Criteria

1. Gestational age of more than 30 weeks;

2. Had chronic hepatitis B virus (HBV) infection;

3. HBV DNA > 200,000 IU/ml;

4. Consecutively normal levels of alanine aminotransferase (< 40 U/L) and total bilirubin (< 17.1 μmol/L);

5. Willing and able to provide written informed consent and adhere to the trial protocol.

Exclusion Criteria

1. Previous treatment to reduce alanine aminotransferase and total bilirubin levels;

2. Previous antiviral treatment for HBV infection (except when antiviral agents were administered for the prevention of perinatal transmission during a previous pregnancy and discontinued more than 6 months before the current pregnancy);

3. Coinfection with hepatitis C, D, E, or human immunodeficiency virus;

4. Previous or current evidence of hepatocellular carcinoma, cirrhosis, systemic or other organ disorders;

5. A hemoglobin level of less than 80 g/L;

6. A neutrophil count of less than 1.0 × 10^9/L;

7. An albumin level of less than 30 g/L;

8. Clinical signs of threatened miscarriage;

9. Evidence of fetal deformity by ultrasound examination and other tests;

10. A history of abortion, pregnancy loss, or congenital malformation in a previous pregnancy;

11. A history of genetic disease(s), including the family member(s);

12. Concurrent treatment with other drugs, including but not limited to nephrotoxic drugs, immune modulators, cytotoxic drugs, nonsteroidal antiinflammatory drugs, or steroids.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Natural Science Foundation of China

OTHER_GOV

Sponsor Role: collaborator

Henan Provincial People's Hospital

OTHER

Sponsor Role: collaborator

The Sixth People's Hospital of Zhengzhou

OTHER

Sponsor Role: collaborator

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital of Xi'an Jiaotong University

OTHER

Sponsor Role: collaborator

Shandong Provincial Hospital

OTHER_GOV

Sponsor Role: collaborator

Luoyang Central Hospital

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Nanyang Medical College

OTHER

Sponsor Role: collaborator

Sixth People's Hospital of Kaifeng

UNKNOWN

Sponsor Role: collaborator

Luohe Central Hospital

UNKNOWN

Sponsor Role: collaborator

Xinyang Central Hospital

OTHER

Sponsor Role: collaborator

Yan'an University Affiliated Hospital

OTHER

Sponsor Role: collaborator

Nanyang Central Hospital

OTHER

Sponsor Role: collaborator

Fifth People's Hospital of Anyang

UNKNOWN

Sponsor Role: collaborator

The First Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role: lead

Responsible Party

Qing-Lei Zeng

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Qing-Lei Zeng

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Zhengzhou University

Central Contacts

Qing-Lei Zeng, M.D.

Role: CONTACT

zengqinglei2009@163.com

86 15838120512

Zu-Jiang Yu, M.D.

Role: CONTACT

johnyuem@zzu.edu.cn

86 186 0371 0022

References

Zeng QL, Zhou YH, Dong XP, Zhang JY, Li GM, Xu JH, Chen ZM, Song N, Zhang HX, Chen RY, Lv XY, Huang S, Li WZ, Pan YJ, Feng YH, Li ZQ, Zhang GF, Lin WB, Zhang GQ, Li GT, Li W, Zeng YL, Zhang DW, Cui GL, Lv J, Liu YM, Liang HX, Sun CY, Wang FS, Yu ZJ. Expected 8-Week Prenatal vs 12-Week Perinatal Tenofovir Alafenamide Prophylaxis to Prevent Mother-to-Child Transmission of Hepatitis B Virus: A Multicenter, Prospective, Open-Label, Randomized Controlled Trial. Am J Gastroenterol. 2025 May 1;120(5):1045-1056. doi: 10.14309/ajg.0000000000003122. Epub 2024 Oct 9.

Reference Type: DERIVED

PMID: 39382852 (View on PubMed)

Other Identifiers

2021-KY-0144-002

Identifier Type: -

Identifier Source: org_study_id