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

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ClinicalTrials.gov Identifier: NCT03476083
Recruitment Status : Recruiting
First Posted : March 23, 2018
Last Update Posted : December 12, 2019
Sponsor:
Information provided by (Responsible Party):
New Discovery LLC

Tracking Information
First Submitted Date  ICMJE March 18, 2018
First Posted Date  ICMJE March 23, 2018
Last Update Posted Date December 12, 2019
Actual Study Start Date  ICMJE June 10, 2018
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2018)		 Assessment on the proportion of infants who are infected with hepatitis B at the age of 28 weeks in the two groups [ Time Frame: From the date of birth to age of 28 weeks. ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2018)
  • Assessment on congenital defects and/or malformation rates in each infant group for comparison [ Time Frame: From the date of birth to age of 28 weeks. ]
    Congenital defects and/or malformation rates are defined as the proportion of infants with the aforementioned abnormalities discovered during the study period.
  • Assessment on the reduction of maternal HBV DNA levels at delivery [ Time Frame: From the date of randomization until delivery. ]
    Assess the reduction of maternal HBV DNA levels at delivery when compared to the baseline before initiating TDF.
  • Maternal serological outcomes during the study: Percentage of mothers who loss/seroconversion of HBsAg or/and HBeAg during the study [ Time Frame: From the date of randomization until postpartum week 28. ]
    Assess the percentage of mothers who loss/seroconversion of HBsAg or/and HBeAg during the study.
  • Adverse events of both mothers and infants [ Time Frame: From the date of screening until postpartum week 28. ]
    Assess the percentage of mothers or infants who have adverse events during the study.
  • Tolerability of TDF therapy: Percentage of mothers who discontinue on TDF therapy due to the adverse event(s) during the study [ Time Frame: From the date of randomization until delivery. ]
    Assess the percentage of mothers who discontinue on TDF therapy due to the adverse event(s) during the study.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2018)
  • Assessment on congenital defects and/or malformation rates in each infant group for comparison [ Time Frame: From the date of birth to age of 28 weeks. ]
    Congenital defects and/or malformation rates are defined as the proportion of infants with the aforementioned abnormalities discovered during the study period.
  • Assessment on the reduction of maternal HBV DNA levels at delivery [ Time Frame: From the date of radomization until delivery. ]
    Assess the reduction of maternal HBV DNA levels at delivery when compared to the baseline before initiating TDF.
  • Maternal serological outcomes during the study: Percentage of mothers who loss/seroconversion of HBsAg or/and HBeAg during the study [ Time Frame: From the date of randomization until postpartum week 28. ]
    Assess the percentage of mothers who loss/seroconversion of HBsAg or/and HBeAg during the study.
  • Adverse events of both mothers and infants [ Time Frame: From the date of screening until postpartum week 28. ]
    Assess the percentage of mothers or infants who have adverse events during the study.
  • Tolerability of TDF therapy: Percentage of mothers who discontinue on TDF therapy due to the adverse event(s) during the study [ Time Frame: From the date of randomization until delivery. ]
    Assess the percentage of mothers who discontinue on TDF therapy due to the adverse event(s) during the study.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tenofovir Disoproxil Fumarate in Combination of Hepatitis B Vaccine for Preventing Hepatitis B Vertical Transmission
Official Title  ICMJE Tenofovir Disoproxil Fumarate in Combination of Hepatitis B Vaccine With the Omission of Immune Globulin to Prevent Hepatitis B Transmission in Mother With High Viral Load: A Multi-Center, Prospective, Randomized and Open-Label Study
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.
Detailed Description

This is a multicenter, prospective, randomized, open-label and parallel two arm study starting from week 14-16 of pregnancy to post-partum week 28. The enrollment from approximately 7 centers will be in blocks for sample balance. By using the randomized table, 280 HBeAg-positive pregnant women with chronic hepatitis B (CHB) will be randomized in a 1:1 ratio in to two arms. Group assignments will be also stratified by the maternal HBV DNA levels >9 log10 versus ≤ 9 log10 IU/mL.

Group A: This is the experimental group. Participating mothers will receive TDF (oral 300 mg tablet 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 (within 12 hours) and additional hepatitis B vaccine at the age of week 4 and week 24. HBIg will be omitted for the infants in this group. However, the birth dose of HBIg will be provided to infants born to mothers who have poor control of maternal viremia (i.e. the levels of HBV DNA >200,000 IU/mL before delivery). Group B: This is the comparative group. Participating mothers will receive TDF (oral 300 mg tablet 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 (within 12 hours) and additional hepatitis B vaccine at the age of week 4 and week 24.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Hepatitis B Infection
  • Congenital Malformation
  • Birth Defect
  • Viremia
  • Chronic Infection
Intervention  ICMJE Drug: Tenofovir Disoproxil Fumarate (TDF) 300 mg oral daily.
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.
Other Names:
  • HBIg 200 IU im for infants in the group B
  • HBV vaccine 10 ug im for all infants
Study Arms  ICMJE
  • Experimental: Group A
    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.
    Intervention: Drug: Tenofovir Disoproxil Fumarate (TDF) 300 mg oral daily.
  • Active Comparator: Group B
    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.
    Intervention: Drug: Tenofovir Disoproxil Fumarate (TDF) 300 mg oral daily.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 22, 2018)		 280
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2024
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 20 Years to 35 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Xiuli Chen, MD +86-13363887189 13363887189@163.com
Contact: Erhei Dai, MD +86-13323119296 daieh2008@126.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03476083
Other Study ID Numbers  ICMJE US-G10-P616
(2018) 462 No: HGRSL20180412 ( Other Identifier: Ministry of Science and Technology of China, HGRM Office )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party New Discovery LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE New Discovery LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Calvin Q Pan, MD Leading Principle Investigator, NYU Langone Health, NYU School of Medicine, NY
Study Director: Erhei Dai, MD The Fifth Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, China
PRS Account New Discovery LLC
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP