Tenofovir in Late Pregnancy to Prevent Vertical Transmission of Hepatitis B Virus

Hepatitis B Infection Clinical Trial

Official title:

Tenofovir Disoproxil Fumarate in Late Pregnancy to Prevent Vertical Transmission of Hepatitis B Virus in Highly Viremic Mothers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01488526
• Other study ID #: IN-US 174-0174
• Status: Completed
• Phase: Phase 4
• Start date: March 1, 2012
• Est. completion date: June 28, 2018

Study information

• Verified date: December 2019
• Source: New Discovery LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Immunoprophylaxis failure of hepatitis B virus (HBV) leading to vertical transmission remains a concern and has been reported in approximately 8-15% of infants born to hepatitis B e antigen (HBeAg) positive mothers with high levels of HBV DNA. Maternal HBV DNA > 6log10 copies/mL (or >200,000 IU/mL) is the major risk for the mother-to-child transmission. Prior observational studies have shown that antiviral therapy including lamivudine or telbivudine use during late pregnancy can safely reduce the rate of vertical transmission in this special population compared to untreated patients.

Tenofovir Disoproxil (TDF), a pregnancy category B medication, reduces HBV DNA and normalizes serum alanine aminotransferase (ALT) in chronic hepatitis B patients (CHB) with few adverse effects. Two aspects on tenofovir use in pregnancy will be evaluated prospectively in this study:

1. The data on its tolerability and safety in HBeAg+ pregnant women with HBV DNA > 6log10 copies/mL (or > 200,000 IU/mL) during late pregnancy and infants.

2. Its efficacy in the reduction of HBV vertical transmission rate.

Description:

Eligible mothers will be randomized (1:1) to either TDF-treated group or untreated group with about 100 subjects in each arm. The treatment group will receive TDF starting at week 30-32 of gestation until week 4 postpartum; follow up will continue until post-partum week 28 and infants age of 28 weeks. Untreated group will receive the standard of care with similar follow-up schedule as the treatment group.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: June 28, 2018
• Est. primary completion date: April 28, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 35 Years

Eligibility

Inclusion Criteria:

• documented CHB infection with HBsAg positive > 6 months

• HBeAg+ CHB pregnant women

• gestational age between 30-32 weeks

• HBV DNA > 6 log10 copies/mL (or >200,000 IU/mL)

• both mother and father of the child are willing to consent for the study

Major Exclusion Criteria:

• co-infection with hepatitis A, C, D, E, HIV-1 or sexually transmitted disease (STD)

• decompensated liver disease or significant co-morbidity

• history of abortion, or diagnosis of fetal defect, or congenital malformation in prior pregnancy

• antiviral used within six months prior to this pregnancy, or history of renal or tubular function impairment due to adefovir.

• requirement for other medication during pregnancy to manage other chronic disease(s) or concurrent treatment with immune-modulators, cytotoxic drugs, or steroids

• the biological father of the child had CHB

• clinical signs of threatened miscarriage in early pregnancy

• evidence of hepatocellular carcinoma

• maternal alanine aminotransferase (ALT) > or = 5 x upper limit of normal (U/mL), or Total Bilirubin > or = 2, or glomerular filtration rate (GFR) < 100, or Albumin < 25 g/L

• evidence of fetal deformity by ultrasound examination

• patient is participating other clinical study

Related Conditions & MeSH terms

• Chronic Infection
• Communicable Diseases
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B Infection
• Infection
• Viremia

Intervention

Drug:
• TDF treatment
About 100 mothers treated with tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum, then observed to the end of the study at post-partum week 28, paired infants received standard HBV prophylaxis.

Locations

Country	Name	City	State
China	Hepatobiliary Disease Hospital of Jilin Province	Chang Chun	Jilin
China	Southwest Hospital	Chongqing	Chongqing
China	The Second Affiliated Hospital of the Southeast University	Nanjing	Jiangsu
China	Nanyang Central Hospital	Nanyang	Henan
China	The Fifth Hospital of Shijiazhuang	Shijiazhuang	Hebei

Sponsors (2)

Lead Sponsor	Collaborator
New Discovery LLC	Gilead Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure the number of infants who have HBV infection at the age of 28 weeks		From the date of birth to age of 28 weeks
Primary	Assessment of the safety and tolerability of TDF, measure the number of participants and paired infants with adverse events		From the date of randomization until 28 weeks of postpartum.
Secondary	Measure maternal HBV DNA reduction during the study period when compared to the baseline		From the date of radomization to the time of delivery (upto 12 weeks from the radomization)
Secondary	Measure maternal HBV DNA reduction during the study period when compared to the baseline		From the date of radomization to the time of delivery (about 8 - 10 weeks from the radomization)
Secondary	percentage of mothers with sero-negativity or sero-conversion of HBsAg and/or HBeAg in each group for comparison		From the date of randomization until 28 weeks of postpartum.