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

NCT01488526 | Completed Phase 4 DMC

• 1 other identifier: IN-US 174-0174
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 5

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

Conditions

Hepatitis B Infection; Chronic Infection; Viremia

Keywords

Hepatitis B; Vertical transmission; Pregnancy; Antiviral treatment

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• 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)

• 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)

• 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.

Study Arms (2)

Control arm: HBIG & vaccine for infants

NO INTERVENTION

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

TDF treatment arm

EXPERIMENTAL

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

Drug: TDF treatment

Interventions

TDF treatment DRUG

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.

Also known as: Viread, Tenofovir, TDF, Hepatitis B-IgG, Hepatitis B vaccine

TDF treatment arm

Eligibility Criteria

• Age: 20 Years - 35 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• New Discovery LLC: lead
• Gilead Sciences: collaborator

Study Sites (5)

Southwest Hospital

Chongqing, Chongqing Municipality, 400038, China

Location

The Fifth Hospital of Shijiazhuang

Shijiazhuang, Hebei, 050021, China

Location

Nanyang Central Hospital

Nanyang, Henan, 473000, China

Location

The Second Affiliated Hospital of the Southeast University

Nanjing, Jiangsu, 210003, China

Location

Hepatobiliary Disease Hospital of Jilin Province

Changchun, Jilin, 130062, China

Location

Related Publications (2)

• 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.

  PMID: 33789963 DERIVED

• 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.

  PMID: 27305192 DERIVED

MeSH Terms

Conditions

Hepatitis B; Persistent Infection; Viremia

Interventions

Tenofovir; Hepatitis B Vaccines

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Calvin Q Pan, MD

  Leading Principle Investigator, Division of Gastroenterology and Hepatology, NYU Langone Medical Center, New York

  STUDY CHAIR

• Zhongping Duan, MD

  Capital Medical University

  STUDY DIRECTOR

• Shuqin Zhang, MD

  Hepatobiliary Disease Hospital of Jilin Province, Jilin, China

  PRINCIPAL INVESTIGATOR

• Erhei Dai, MD

  The Fifth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China

  PRINCIPAL INVESTIGATOR

• Guorong Han, MD

  The Second Affiliated Hospital of the Southeast University, Nanjing, China

  PRINCIPAL INVESTIGATOR

• Huaihong Zhang, MD

  Nanyang Central Hospital, Nanyang, Henan, China

  PRINCIPAL INVESTIGATOR

• Yuming Wang, MD

  Southwest Hospital, Chongqing, Chongqing, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2011
• First Posted: December 8, 2011
• Study Start: March 1, 2012
• Primary Completion: April 28, 2014
• Study Completion: June 28, 2018
• Last Updated: December 9, 2019

Record last verified: 2019-12

Locations

CN (5)