Clinical trial NCT01488526: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis B Infection
Chronic Infection
Viremia
Keywords: Hepatitis B
Vertical transmission
Pregnancy
Antiviral treatment
Lead sponsor: New Discovery LLC
Sponsor class: INDUSTRY
Collaborators: name: Gilead Sciences
First posted: 2011-12-08
Enrollment: 200
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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:

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.

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.

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

Primary outcomes:
measure: Measure the number of infants who have HBV infection at the age of 28 weeks
timeFrame: From the date of birth to age of 28 weeks
measure: Assessment of the safety and tolerability of TDF, measure the number of participants and paired infants with adverse events
timeFrame: From the date of randomization until 28 weeks of postpartum.
Secondary outcomes:
measure: Measure maternal HBV DNA reduction during the study period when compared to the baseline
timeFrame: From the date of radomization to the time of delivery (upto 12 weeks from the radomization)
measure: Measure maternal HBV DNA reduction during the study period when compared to the baseline
timeFrame: From the date of radomization to the time of delivery (about 8 - 10 weeks from the radomization)
measure: percentage of mothers with sero-negativity or sero-conversion of HBsAg and/or HBeAg in each group for comparison
timeFrame: From the date of randomization until 28 weeks of postpartum.
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Southwest Hospital
state: Chongqing
city: Shijiazhuang
country: China
facility: The Fifth Hospital of Shijiazhuang
state: Hebei
city: Nanyang
country: China
facility: Nanyang Central Hospital
state: Henan
city: Nanjing
country: China
facility: The Second Affiliated Hospital of the Southeast University
state: Jiangsu
city: Chang Chun
country: China
facility: Hepatobiliary Disease Hospital of Jilin Province
state: Jilin
Study officials:
affiliation: Leading Principle Investigator, Division of Gastroenterology and Hepatology, NYU Langone Medical Center, New York
name: Calvin Q Pan, MD
role: STUDY_CHAIR
affiliation: Capital Medical University
name: Zhongping Duan, MD
role: STUDY_DIRECTOR
affiliation: Hepatobiliary Disease Hospital of Jilin Province, Jilin, China
name: Shuqin Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Fifth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China
name: Erhei Dai, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Second Affiliated Hospital of the Southeast University, Nanjing, China
name: Guorong Han, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nanyang Central Hospital, Nanyang, Henan, China
name: Huaihong Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Southwest Hospital, Chongqing, Chongqing, China
name: Yuming Wang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pan CQ, Dai E, Duan Z, Han G, Zhao W, Wang Y, Zhang H, Zhu B, Jiang H, Zhang S, Zhang X, Zou H, Chen X, Chen Y. Long-term safety of infants from mothers with chronic hepatitis B treated with tenofovir disoproxil in China. Gut. 2022 Apr;71(4):798-806. doi: 10.1136/gutjnl-2020-322719. Epub 2021 Mar 31.
citation: Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, Zhang H, Zou H, Zhu B, Zhao W, Jiang H; China Study Group for the Mother-to-Child Transmission of Hepatitis B. Tenofovir to Prevent Hepatitis B Transmission in Mothers with High Viral Load. N Engl J Med. 2016 Jun 16;374(24):2324-34. doi: 10.1056/NEJMoa1508660.