Chronic HBV Infection in Pregnant Women Taking TAF to Prevent Vertical Transmission

NCT04237376 | Unknown FDA Drug

• 1 other identifier: 2017ZX10201201-001
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 4

Brief Summary

Mother-to-child transmission is the main route of transmission of Hepatitis B Virus (HBV) in China, and about 30% - 50% of chronic HBV carriers are infected by this. Although the current hepatitis B vaccine combined with hepatitis B immunoglobulin scheme has achieved excellent results, about 5% - 10% of infants born to chronic hepatitis B (CHB) mothers are still infected. A pregnant women's blood hepatitis B virus load ≥ 2 × 10\^5 IU/mL before delivery is the main risk factor for transmission prevention failure. Two recent random controlled trial (RCT) studies have shown that the use of Tenofovir Disoproxil Fumarate (TDF) in highly viremic HBsAg positive mothers may safely reduce the rate of MTCT in comparisons between groups of TDF treated and untreated patients. Tenofovir Alafenamide (TAF) is the successor to TDF, and both drugs have a similar mechanism of action to reduce HBV DNA levels and normalize serum alanine aminotransferase (ALT) in chronic hepatitis B patients (CHB). TAF however, has a better safety profile with less adverse effects to hip and spine bone mineral density and renal function. Currently, TAF has been approved by the State Food and Drug Administration and marketed in China in December 2018. On the drug label, it has been suggested that TAF may be considered during pregnancy if necessary. However, it has not been reported whether the application of TAF in pregnant women can achieve better effects and safety in prevention of mother-to-child transmission. This prospective, triple arm, multicenter study seeks to evaluate the efficacy and safety of TAF in the prevention of mother-to-child transmission as compared to a retrospective cohort of mothers who were treated with TDF.

Conditions

Hepatitis B, Chronic; Pregnancy Related

Outcome Measures

Primary Outcomes (3)

• 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 three study arms 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 the age of 24-28 weeks

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

  Congenital defects and/or malformation rates are defined as the proportion of infants with the aforementioned abnormalities discovered during the study period. The proportion of infants who experience congenital defects and/or malformation as determined in all respective groups will be compared.

  From the date of birth to age of 28 weeks

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

  To evaluate the frequency of treatment discontinuation in patients who could not tolerate TDF/TAF therapy due to adverse event(s) during the study. The proportion of mothers who discontinue TAF therapy as determined in all respective groups will be compared.

  Gestational week 28 through delivery of their infant, on average at gestational week 36.

Secondary Outcomes (5)

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

  At delivery

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

  Gestational week 24-28 week to postpartum week 28

• Incidence of Treatment-Emergent Adverse Events in Mothers as Stratified by the CTCAE v 5.0

  Gestational week 24-28 until Postpartum Week 28

• Incidence of Treatment-Emergent Adverse Events in Infants as Stratified by the CTCAE v 5.0

  At birth until Infant age Week 28

• Percentage of Mothers with Alanine transferase (ALT) levels within the normal limit

  Gestational week 24-28 until Postpartum week 28

Study Arms (3)

Treatment Arm A: CHB Mothers treated with TAF during Pregnancy

120 pregnant women with double positive HBsAg and HBeAg and HBV DNA levels ≥ 2 × 10\^6 IU/mL were recruited from all four treatment centers. Mothers were enrolled and observed from gestational week 24-28 until postpartum week 28, and treated with TAF (25mg oral daily) from gestational week 28 until delivery (if the liver function is significantly abnormal after delivery, that is, ALT ≥ 5 × Upper Limit of Normal (ULN), the oral antiviral drug can be continued according to the wishes of the pregnant woman and the test results). All babies were given 3 HBV vaccines (0, 1, 6) and 1 routine Hepatitis B immunoglobin (HBIG) after birth. All babies were followed up to 2 years. According to the mother's wishes, if the mother agrees to collect breast milk and determine TAF concentration, breast milk was collected every day, and continuously collected 5-7 days for TAF concentration measurement. The time of last TAF dose taken as well as the time between milk collection and delivery was recorded.

Drug: Tenofovir Alafenamide 25 MG

Comparative Arm C: CHB Pregnant Mothers

This arm C consists of 360 cases of pregnant women with HBsAg and HBeAg double-positive, and HBV DNA level ≥ 2 × 10\^6 IU/mL. The mothers in this historical cohort did not receive any antiviral treatment during their pregnancy. All cases of pregnant mothers in this arm were extracted from the four treatment centers involved in this study: Beijing You'an Hospital, Capital Medical University, Fourth Hospital Affiliated to Harbin Medical University, Third Hospital of Qinhuangdao, and Tongliao Infectious Disease Hospital. All babies received 3 doses of HBV vaccine (0, 1, 6) and 1 dose of HBIG after birth.

Comparative Arm B: CHB Pregnant Mothers treated with TDF

This retrospective cohort arm B consists of 120 cases of pregnant women with double-positive HBsAg and HBeAg and HBV DNA levels ≥ 2 × 10\^6 IU/mL. All cases of pregnant mothers in this arm were extracted from the four treatment centers involved in this study: Beijing You'an Hospital, Capital Medical University, Fourth Hospital Affiliated to Harbin Medical University, Third Hospital of Qinhuangdao, and Tongliao Infectious Disease Hospital. Pregnant mothers were treated with TDF (300mg oral daily) starting from gestational week 28 and discontinued the drug at delivery. All babies received 3 doses of HBV vaccine (0, 1, 6) and 1 dose of HBIG after birth.

Drug: Tenofovir Disoproxil Fumarate 300 MG Oral Tablet

Interventions

Tenofovir Alafenamide 25 MG DRUG

Tenofovir Alafenamide 25 mg, per oral daily was taken by CHB pregnant mothers with viral load ≥ 2 × 10\^6 IU / mL from gestational week 28 to delivery of infant to prevent MTCT.

Also known as: Vemlidy

Treatment Arm A: CHB Mothers treated with TAF during Pregnancy

Tenofovir Disoproxil Fumarate 300 MG Oral Tablet DRUG

Tenofovir Disoproxil Fumarate 300 mg, per oral daily was taken by CHB pregnant mothers with viral load ≥ 2 × 10\^6 IU / mL from gestational week 28 to delivery of infant to prevent MTCT.

Also known as: Viread

Comparative Arm B: CHB Pregnant Mothers treated with TDF

Eligibility Criteria

• Age: 20 Years - 35 Years
• Gender Eligibility Details: Patients must be of the female sex, and be pregnant with a child at the time of enrollment.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

A total of 600 (120 TAF arm A, 120 TDF arm B, 360 arm C) CHB pregnant mothers with high HBV DNA viremic load, i.e. ≥ 2 × 10\^6 IU/mL, were included in this study spanning four centers. 120 mothers were prospectively enrolled to take TAF 25 mg per oral at four centers and 120 mothers were prospectively enrolled to take TDF 300mg per oral only at Beijing Youan Hospital, both arms from gestational week 28 until delivery of their infant (if the liver function is abnormal at delivery, ie ALT≥5×ULN, the treatment can be continued according to the wishes of the pregnant woman and the laboratory tests). A historical cohort of 360 consecutive highly viremic mothers who received no antiviral treatment at Beijing Youan Hospital will be retrospective enrolled as the control group.

You may qualify if:

• Positive Serum tests for both HBsAg and HBeAg
• HBV DNA viremic load ≥ 2 × 10\^6 IU/mL
• Mother must be between 20 and 35 years old
• Mother must undergo perinatal testing and delivery at their respective study institution
• Mother must maintain good compliance to study protocols/instructions, as well as any necessary interventions as determined by the local study investigative team.
• Patient must understand and willingly sign an informed consent form provided at enrollment.

You may not qualify if:

• Co-infection with the following diseases: HIV-1, Hepatitis A Virus, Hepatitis C Virus, Hepatitis D Virus, Hepatitis E Virus infections or sexually transmitted diseases.
• History of miscarriage or congenital malformations in any previous pregnancy.
• Previous antiviral treatment (except the use of antiviral drugs to prevent MTCT in previous pregnancy and antiviral drugs that have been discontinued for more than 6 months before this pregnancy)
• Previous renal dysfunction
• Liver cancer or liver decompensation
• Creatinine clearance \<100 mL / min
• Hypophosphatemia
• Hemoglobin \<80g / L
• Neutrophil count \<1 × 10 \^ 9 / L
• ALT (U/L) greater than 5x the upper limit of normal
• Total bilirubin \> 34.2 umol / L
• Albumin \<25g / L
• Any clinical risk/signs of abortion
• Concurrent use of nephrotoxic drugs, steroids, cytotoxic drugs, non-steroidal anti-inflammatory drugs or immune modulators
• Spouse has chronic hepatitis B

Sponsors & Collaborators

• New Discovery LLC: lead

Study Sites (4)

Beijing You'an Hospital, Capital Medical University

Beijing, Beijing Municipality, 100069, China

RECRUITING

The Third Hospital of Qinhuangdao City

Qinhuangdao, Hebei, 066000, China

RECRUITING

Department of Infectious Disease,The Fourth Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150001, China

RECRUITING

Tongliao Infectious Disease Hospital

Tongliao, Inner Mongolia, 028000, China

RECRUITING

Related Publications (6)

• Jourdain G, Ngo-Giang-Huong N, Harrison L, Decker L, Khamduang W, Tierney C, Salvadori N, Cressey TR, Sirirungsi W, Achalapong J, Yuthavisuthi P, Kanjanavikai P, Na Ayudhaya OP, Siriwachirachai T, Prommas S, Sabsanong P, Limtrakul A, Varadisai S, Putiyanun C, Suriyachai P, Liampongsabuddhi P, Sangsawang S, Matanasarawut W, Buranabanjasatean S, Puernngooluerm P, Bowonwatanuwong C, Puthanakit T, Klinbuayaem V, Thongsawat S, Thanprasertsuk S, Siberry GK, Watts DH, Chakhtoura N, Murphy TV, Nelson NP, Chung RT, Pol S, Chotivanich N. Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B. N Engl J Med. 2018 Mar 8;378(10):911-923. doi: 10.1056/NEJMoa1708131.

  PMID: 29514030 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

• Chen HL, Lee CN, Chang CH, Ni YH, Shyu MK, Chen SM, Hu JJ, Lin HH, Zhao LL, Mu SC, Lai MW, Lee CL, Lin HM, Tsai MS, Hsu JJ, Chen DS, Chan KA, Chang MH; Taiwan Study Group for the Prevention of Mother-to-Infant Transmission of HBV (PreMIT Study); Taiwan Study Group for the Prevention of Mother-to-Infant Transmission of HBV PreMIT Study. Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to-infant transmission of hepatitis B virus. Hepatology. 2015 Aug;62(2):375-86. doi: 10.1002/hep.27837. Epub 2015 May 13.

  PMID: 25851052 BACKGROUND

• Chan HL, Fung S, Seto WK, Chuang WL, Chen CY, Kim HJ, Hui AJ, Janssen HL, Chowdhury A, Tsang TY, Mehta R, Gane E, Flaherty JF, Massetto B, Gaggar A, Kitrinos KM, Lin L, Subramanian GM, McHutchison JG, Lim YS, Acharya SK, Agarwal K; GS-US-320-0110 Investigators. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016 Nov;1(3):185-195. doi: 10.1016/S2468-1253(16)30024-3. Epub 2016 Sep 22.

  PMID: 28404091 BACKGROUND

• Buti M, Gane E, Seto WK, Chan HL, Chuang WL, Stepanova T, Hui AJ, Lim YS, Mehta R, Janssen HL, Acharya SK, Flaherty JF, Massetto B, Cathcart AL, Kim K, Gaggar A, Subramanian GM, McHutchison JG, Pan CQ, Brunetto M, Izumi N, Marcellin P; GS-US-320-0108 Investigators. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016 Nov;1(3):196-206. doi: 10.1016/S2468-1253(16)30107-8. Epub 2016 Sep 22.

  PMID: 28404092 BACKGROUND

• Zou H, Zhu L, Cao L, Suo S, Zhu Y, Wang Y, Dong J, Han B, Duan Z, Chen Y, Pan CQ. Vertical Transmission in Mothers Taking TAF With Exceptionally High Viral Load. J Viral Hepat. 2025 Mar;32(3):e70000. doi: 10.1111/jvh.70000.

  PMID: 39953819 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

tenofovir alafenamide; Tenofovir; Tablets

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Zhongping Duan, MD

  Capital Medical University, Beijing You'an Hospital

  PRINCIPAL INVESTIGATOR

• Calvin Q Pan, MD

  NYU Langone Health

  STUDY CHAIR

Central Study Contacts

Huaibin Zou, MD

CONTACT

+86-13720084736; zhbin03@126.com

Zhongping Duan, MD

CONTACT

+86-13366425670; duan2517@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2019
• First Posted: January 23, 2020
• Study Start: April 9, 2019
• Primary Completion: September 30, 2020
• Study Completion: September 30, 2020
• Last Updated: January 23, 2020

Record last verified: 2020-01

Locations

CN (4)