Clinical trial NCT04850950: Tenofovir Alafenamide to Prevent Perinatal Transmission of Hepatitis B
Official title: Safety and Efficacy of Tenofovir Alafenamide to Prevent Perinatal Transmission of Hepatitis B (TAF-PPT): A Multicentre, Prospective, Open-label, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Hepatitis B
Mother-to-Child Transmission
Safety
Efficacy
Hepatitis B Virus
Tenofovir Alafenamide Fumarate
Lead sponsor: The First Affiliated Hospital of Zhengzhou University
Sponsor class: OTHER
Collaborators: name: National Natural Science Foundation of China
name: Henan Provincial People's Hospital
name: The Sixth People's Hospital of Zhengzhou
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Second Affiliated Hospital of Xi'an Jiaotong University
name: Shandong Provincial Hospital
name: Luoyang Central Hospital
name: First Affiliated Hospital of Nanyang Medical College
name: Sixth People's Hospital of Kaifeng
name: Luohe Central Hospital
name: Xinyang Central Hospital
name: Yan'an University Affiliated Hospital
name: Nanyang Central Hospital
name: Fifth People's Hospital of Anyang
First posted: 2021-04-20
Enrollment: 240
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Birth defects.
timeFrame: From prenatal tenofovir alafenamide exposure to the birth and postnatal period up to 7 months of age.
measure: The rate of perinatal transmission of hepatitis B virus.
timeFrame: At 7 months of age.
Secondary outcomes:
measure: Adverse events.
timeFrame: From prenatal tenofovir alafenamide exposure to the delivery (birth) and postnatal period up to 7 months (of age).
measure: Alanine aminotransferase flare.
timeFrame: At postpartum month 7.
measure: Infants' growth.
timeFrame: At birth and 7 months of age.
measure: HBV DNA level.
timeFrame: Immediately before or at delivery.
measure: Hepatitis B e antigen status.
timeFrame: At postpartum month 7.
measure: Hepatitis B surface antigen status.
timeFrame: At postpartum month 7.
Other outcomes:
Locations:
Study officials:
affiliation: The First Affiliated Hospital of Zhengzhou University
name: Qing-Lei Zeng
role: PRINCIPAL_INVESTIGATOR
References: