Tenofovir Disoproxil Fumarate in Combination of Hepatitis B Vaccine for Preventing Hepatitis B Vertical Transmission

NCT03476083 | Unknown Phase 4 DMC FDA Drug

• 2 other identifiers: US-G10-P616(2018) 462 No: HGRSL20180412
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 7

Brief Summary

Immunoprophylaxis with two hepatitis B vaccinations following the hepatitis B immune globulin (HBIg) and hepatitis B vaccine at birth is largely effective in protecting infants from hepatitis B virus (HBV) infection. However, hepatitis B infection due to immunoprophylaxis failure often occurs in approximately 10% of infants who are born to highly viremic mothers with HBeAg-positive. Maternal HBV DNA \> 200,000 IU/mL is the major independent risk for mother-to-child transmission (MTCT). A recent randomized controlled trial has shown that Tenofovir Disoproxil Fumarate (TDF) use during the third trimester of pregnancy could safely reduce the rate of MTCT with few adverse effects when combined with the administration of the standard immunoprophylaxis to the infants. However, HBIg is expensive and not available in many developing countries, resulting approximately 30% of infant infection when they received only HBV vaccination. The present study aims to investigate if highly viremic mothers who are treated with TDF from the second trimester to delivery in combination of infant's standard series of HBV vaccinations (omission of HBIg) have a comparable MTCT rates, when compared to those of mothers who receive TDF at the third trimester in combination of infant's standard HBV vaccinations and a birth dose of HBIg.

Conditions

Hepatitis B Infection; Congenital Malformation; Birth Defect; Viremia; Chronic Infection

Keywords

Mother to Child Transmission; Hepatitis B Infection; Congenital Defects or Malformation; Hepatitis B Vaccine; Hepatitis B Immunoglobulin; Pregnancy; Antiviral Treatment

Outcome Measures

Primary Outcomes (1)

• Assessment on the proportion of infants who are infected with hepatitis B at the age of 28 weeks in the two groups

  Compare MTCT rates between the two study groups and demonstrate non-inferiority in efficacy. MTCT rate is defined as the proportion of infants with serum HBV DNA \>20 IU/mL and/or HBsAg positivity at 28 weeks of age.

  From the date of birth to age of 28 weeks.

Secondary Outcomes (5)

• Assessment on congenital defects and/or malformation rates in each infant group for comparison

  From the date of birth to age of 28 weeks.

• Assessment on the reduction of maternal HBV DNA levels at delivery

  From the date of randomization until delivery.

• Maternal serological outcomes during the study: Percentage of mothers who loss/seroconversion of HBsAg or/and HBeAg during the study

  From the date of randomization until postpartum week 28.

• Adverse events of both mothers and infants

  From the date of screening until postpartum week 28.

• Tolerability of TDF therapy: Percentage of mothers who discontinue on TDF therapy due to the adverse event(s) during the study

  From the date of randomization until delivery.

Study Arms (2)

Group A

EXPERIMENTAL

This is the experimental group. Participating mothers will receive Tenofovir Disoproxil Fumarate (TDF) 300 mg oral daily, starting at gestational weeks 14-16 and continue until delivery. The mothers will be followed together with their infants until postpartum week 28. Infants will receive hepatitis B vaccine at birth and additional hepatitis B (HBV) vaccine at the age of week 4 and week 24. HBIg will be omitted for the infants in this group.

Drug: Tenofovir Disoproxil Fumarate (TDF) 300 mg oral daily.

Group B

ACTIVE COMPARATOR

This is the comparative group. Participating mothers will receive Tenofovir Disoproxil Fumarate (TDF) 300 mg oral daily, starting at gestational weeks 28 and continue until delivery. Patients in group B will have similar follow-up schedules as those in the experimental group. Infants will receive hepatitis B vaccine plus HBIg at birth and additional hepatitis B vaccine at the age of week 4 and week 24.

Drug: Tenofovir Disoproxil Fumarate (TDF) 300 mg oral daily.

Interventions

Tenofovir Disoproxil Fumarate (TDF) 300 mg oral daily. DRUG

All mothers will receive TDF therapy. However, group A will initiate TDF at the gestational week of 14-16, while group B will initiate TDF at the gestational week of 28. All infants will receive a series of three hepatitis B vaccines (at birth, age of weeks 4 and 24). In addition, the infants in the group B will receive HBIg injection at birth.

Also known as: HBIg 200 IU im for infants in the group B, HBV vaccine 10 ug im for all infants

Group A; Group B

Eligibility Criteria

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

You may qualify if:

• HBeAg-positive CHB mothers
• Age of 20-35 years old
• Serum HBV DNA levels \> 200,000 IU/mL
• Gestational age between 12-14 weeks.
• Both mother and father of the child have the ability to understand and are willing to consent to the study.

You may not qualify if:

• Co-infection with (HIV)-1, or hepatitis A, C, D, E or sexual transmitted diseases (STD)
• History of abortion or congenital malformation in a prior pregnancy
• Treatment experience (except when antivirals were used for MTCT prevention in a previous pregnancy and discontinued \>6 months prior to the current pregnancy)
• History of renal dysfunction; evidence of liver cancer or decompensation
• Estimated creatinine clearance (CLCr) \<100 mL/min (using the Cockcroft-Gault method based on serum creatinine and ideal body weight)
• Hypo-phosphoremia; hemoglobin \<8 g/dL; neutrophil count \<1,000//μL; alanine aminotransferase \>5 times upper limit of the normal; total bilirubin \>2 mg/dL; albumin \<25gm/L;
• Clinical signs of threatened miscarriage
• Ultrasonographic evidence of fetal deformity
• Concurrent treatment with nephrotoxic drugs, steroids, cytotoxic drugs, nonsteroidal anti-inflammatory drugs, or immune modulators;
• Recipient of solid organ or bone marrow transplant
• Significant renal, cardiovascular, pulmonary, neurological disease or other health conditions in the opinion of the investigator
• Fetus's biological father had CHB infection

Sponsors & Collaborators

• New Discovery LLC: lead

Study Sites (7)

Beijing Youan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100069, China

RECRUITING

Southwest Hospital

Chongqing, Chongqing Municipality, 400038, China

RECRUITING

Guangzhou Women and Children's Medical Center, Guangzhou Medical University

Guangzhou, Guangdong, 510623, China

RECRUITING

The Fifth Hospital of Shijiazhuang

Shijiazhuang, Hebei, 050021, China

RECRUITING

Shijiazhuang Maternal and Child Health Care Hospital

Shijiazhuang, Hebei, 050051, China

RECRUITING

Department of Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

RECRUITING

The Third People's Hospital of Shenzhen

Shenzhen, Shenzhen, 518112, China

RECRUITING

Related Publications (8)

• Ott JJ, Stevens GA, Wiersma ST. The risk of perinatal hepatitis B virus transmission: hepatitis B e antigen (HBeAg) prevalence estimates for all world regions. BMC Infect Dis. 2012 Jun 9;12:131. doi: 10.1186/1471-2334-12-131.

  PMID: 22682147 BACKGROUND

• Pan CQ, Duan ZP, Bhamidimarri KR, Zou HB, Liang XF, Li J, Tong MJ. An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus. Clin Gastroenterol Hepatol. 2012 May;10(5):452-9. doi: 10.1016/j.cgh.2011.10.041. Epub 2011 Nov 9.

  PMID: 22079509 BACKGROUND

• Pande C, Sarin SK, Patra S, Kumar A, Mishra S, Srivastava S, Bhutia K, Gupta E, Mukhopadhyay CK, Dutta AK, Trivedi SS. Hepatitis B vaccination with or without hepatitis B immunoglobulin at birth to babies born of HBsAg-positive mothers prevents overt HBV transmission but may not prevent occult HBV infection in babies: a randomized controlled trial. J Viral Hepat. 2013 Nov;20(11):801-10. doi: 10.1111/jvh.12102. Epub 2013 Apr 23.

  PMID: 24168259 BACKGROUND

• Lee LY, Aw MM, Saw S, Rauff M, Tong PY, Lee GH. Limited benefit of hepatitis B immunoglobulin prophylaxis in children of hepatitis B e antigen-negative mothers. Singapore Med J. 2016 Oct;57(10):566-569. doi: 10.11622/smedj.2015194. Epub 2015 Dec 29.

  PMID: 26778725 BACKGROUND

• Machaira M, Papaevangelou V, Vouloumanou EK, Tansarli GS, Falagas ME. Hepatitis B vaccine alone or with hepatitis B immunoglobulin in neonates of HBsAg+/HBeAg- mothers: a systematic review and meta-analysis. J Antimicrob Chemother. 2015 Feb;70(2):396-404. doi: 10.1093/jac/dku404. Epub 2014 Oct 31.

  PMID: 25362571 BACKGROUND

• 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 BACKGROUND

• Pan, C. Q.; Chang, T. T.; Bae, S. H.; Brunetto, M.; Coffin, C.; Lau, A.; Mo, S.; Flaherty, J. F.; Gaggar, A.; Subramanian, G. M.; Nguyen, M. H.; Gurel, S.; Thompson, A.; Gane, E. J. Viral kinetics in women of child bearing potential with chronic hepatitis B virus following treatment with tenofovir alafenamide or tenofovir disoproxil fumarate. J Hepatol. 2017;66 S258-S259.

  BACKGROUND

• Pan CQ, Dai E, Mo Z, Zhang H, Zheng TQ, Wang Y, Liu Y, Chen T, Li S, Yang C, Wu J, Chen X, Zou H, Mei S, Zhu L. Tenofovir and Hepatitis B Virus Transmission During Pregnancy: A Randomized Clinical Trial. JAMA. 2025 Feb 4;333(5):390-399. doi: 10.1001/jama.2024.22952.

  PMID: 39540799 DERIVED

MeSH Terms

Conditions

Hepatitis B; Congenital Abnormalities; Viremia; Persistent Infection

Interventions

Tenofovir; hepatitis B hyperimmune globulin

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Calvin Q Pan, MD

  Leading Principle Investigator, NYU Langone Health, NYU School of Medicine, NY

  STUDY CHAIR

• Erhei Dai, MD

  The Fifth Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, China

  STUDY DIRECTOR

Central Study Contacts

Xiuli Chen, MD

CONTACT

+86-13363887189; 13363887189@163.com

Erhei Dai, MD

CONTACT

+86-13323119296; daieh2008@126.com

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: March 18, 2018
• First Posted: March 23, 2018
• Study Start: June 10, 2018
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2024
• Last Updated: December 12, 2019

Record last verified: 2019-12

Locations

CN (7)