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

Primary Purpose

Hepatitis B Infection, Chronic Infection, Viremia

Status

Completed

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

TDF treatment

About this trial

This is an interventional prevention trial for Hepatitis B Infection focused on measuring Hepatitis B, Vertical transmission, Pregnancy, Antiviral treatment

Eligibility Criteria

20 Years - 35 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Southwest Hospital
The Fifth Hospital of Shijiazhuang
Nanyang Central Hospital
The Second Affiliated Hospital of the Southeast University
Hepatobiliary Disease Hospital of Jilin Province

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Control arm: HBIG & vaccine for infants

TDF treatment arm

Arm Description

Provide standard of care to mothers and standard immunoprophylaxis to their infants

tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum for mothers and standard immunoprophylaxis to their infants

Outcomes

Primary Outcome Measures

Measure the number of infants who have HBV infection at the age of 28 weeks

Assessment of the safety and tolerability of TDF, measure the number of participants and paired infants with adverse events

Secondary Outcome Measures

Measure maternal HBV DNA reduction during the study period when compared to the baseline

percentage of mothers with sero-negativity or sero-conversion of HBsAg and/or HBeAg in each group for comparison

Full Information

NCT ID

NCT01488526

First Posted

November 30, 2011

Last Updated

December 6, 2019

Sponsor

New Discovery LLC

Collaborators

Gilead Sciences

1. Study Identification

Unique Protocol Identification Number

NCT01488526

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Completed

Study Start Date

March 1, 2012 (Actual)

Primary Completion Date

April 28, 2014 (Actual)

Study Completion Date

June 28, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

New Discovery LLC

Collaborators

Gilead Sciences

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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: 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. Its efficacy in the reduction of HBV vertical transmission rate.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis B Infection, Chronic Infection, Viremia

Keywords

Hepatitis B, Vertical transmission, Pregnancy, Antiviral treatment

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

200 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Control arm: HBIG & vaccine for infants

Arm Type

No Intervention

Arm Description

Provide standard of care to mothers and standard immunoprophylaxis to their infants

Arm Title

TDF treatment arm

Arm Type

Experimental

Arm Description

tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum for mothers and standard immunoprophylaxis to their infants

Intervention Type

Drug

Intervention Name(s)

TDF treatment

Other Intervention Name(s)

Viread, Tenofovir, TDF, Hepatitis B-IgG, Hepatitis B vaccine

Intervention Description

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.

Primary Outcome Measure Information:

Title

Measure the number of infants who have HBV infection at the age of 28 weeks

Time Frame

From the date of birth to age of 28 weeks

Title

Assessment of the safety and tolerability of TDF, measure the number of participants and paired infants with adverse events

Time Frame

From the date of randomization until 28 weeks of postpartum.

Secondary Outcome Measure Information:

Title

Measure maternal HBV DNA reduction during the study period when compared to the baseline

Time Frame

From the date of radomization to the time of delivery (upto 12 weeks from the radomization)

Title

Measure maternal HBV DNA reduction during the study period when compared to the baseline

Time Frame

From the date of radomization to the time of delivery (about 8 - 10 weeks from the radomization)

Title

percentage of mothers with sero-negativity or sero-conversion of HBsAg and/or HBeAg in each group for comparison

Time Frame

From the date of randomization until 28 weeks of postpartum.

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

35 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials: