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Hepatitis B, ChronicNCT04211805

Maternal Therapy With TAF Versus TDF to Prevent Vertical Transmission of Hepatitis B

An observational study of Hepatitis B, Chronic and Pregnancy Related, run by New Discovery LLC at 11 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Immunoprophylaxis failure of hepatitis B (HBV) remains a concern and has been reported in approximately 10-30% of infants born to highly viremic mothers with HBeAg-positive. Maternal HBV DNA >6log10 copies/mL (or 200,000 IU/mL) is the major independent risk for mother-to-child transmission (MTCT). Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Hepatitis B, Chronic, Pregnancy Related
What is being tested?
Tenofovir Alafenamide 25 MG for arm (A) and Tenofovir Disoproxil Fumarate 300mg for arm (B)
How many people
450 participants
Where
11 sitesChina
Study dates
27 Jan 2020to 30 Sep 2021
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Study population: 225 consecutive chronically infected hepatitis B mothers who are willing to receive tenofovir alafenamide (TAF) treatment and another consecutive 225 who are willing to receive tenofovir disoproxil fumarate (TDF) treatment at eleven centers across China for high viremic load during pregnancy will be enrolled and followed prospectively for data collection. These patients underwent TAF/TDF treatment in their respective care centers and will be grouped together in Group A for TAF treatment and Group B for TDF treatment for primary and secondary analysis.

Who may be able to join

  • Pregnant female, above 18 years of age and under 40 years of age.
  • Gestational age between 12-14 weeks (The screening on patients can be started at gestational week 12).
  • Documented compensated and stable chronic hepatitis B defined by all of the following:
  • HBsAg persistently positive > 6 months.
  • Clinical history, physical findings, and test results are compatible with compensated chronic hepatitis B.
  • Detectable maternal serum HBsAg and HBeAg at the screening visit.
Show all 9Show fewer
  • Maternal serum HBV DNA levels exceeding 200,000 IU/mL by the COBAS Amplicor HBV PCR assay at screening visits.
  • Patient is willing and able to comply with the study drug regimen and all other study requirements. Patient is also willing to prevent another pregnancy in 28 weeks after delivery of the current baby.
  • Patient and her husband (both father and mother of the child) understand the risk and are willing to have the mother participating in the study. The mother must be willing and able to provide written informed consent to participate in the study.

Who cannot join

  • Patients will be excluded if they have any one of the following:
  • Creatinine clearance <100 mL/min (using the Cockcroft-Gault method based on serum creatinine and ideal body weight) or hypo-phosphoremia (below normal range).
  • History of renal events on adefovir or history of resistance to adefovir.
  • Hemoglobin <8 g/dL, or neutrophil count <1000/uL, or ALT >5 times ULN, or total bilirubin >2 mg/dL; or albumin <25gm/L, or abnormal creatinine level, or abnormal BUN levels.
  • History of abortion, or congenital malformation, or child infected with HBV in a prior pregnancy.
  • Biological father of the child (current pregnancy) has CHB.
  • Significant renal, cardiovascular, pulmonary, or neurological disease that may impact the subject's participation in the study as per the opinion of the investigator.

Trial locations and contacts

11 sites in 1 country.

Harry Huang, BS contact

(+1)5163048196

harry.huang887@gmail.com

Calvin Q Pan, MD contact

(+86)15920560416

Panc01@nyu.edu

11 sites in 1 country

China11 sites, 11 recruiting

  • Xiangya Hospital, Central South University

    Changsha, Hunan

    Yan Huang, MD, (+86)13874854142, drhyan@163.com

    Zebing Huang, MD, (+86)13574193630, 36165934@qq.com

    Recruiting

  • First Affiliated Hospital of Fujian Medical University

    Fuzhou, Fujian

    Qi Zheng, MD, (+86)13705978902, bei0825@163.com

    Xiao Y Lin, MS, (+86)15060065681, xiaoyulin1986@.sina.cn

    Recruiting

  • Ganzhou Fifth People's Hospital

    Ganzhou, Jiangxi

    Huizhen Hong, (+86)13607964566

    Lijuan Long, MD, (+86)13766392668

    Recruiting

  • Hainan General Hospital

    Haikou, Hainan

    Jiao Wang, MD, (+86)18084671251, 517538898@qq.com

    Furong Xiao, MD, +8613907599107, 16851333@qq.com

    Recruiting

  • The Fourth Hospital of Harbin Medical University

    Harbin, Heilonjiang

    Lei Yu, MD, (+86)13804535457, widedoor@sina.com

    Linying Zhu, MD, (+86)13199561586, zlyhmu@163.com

    Recruiting

  • Shanghai Public Health Clinical Center, Fudan University

    Jinshan, Shanghai Municipality, 201508

    Min-min Sheng, MD, (+86)18930817262, shengminmin@shphc.org.cn

    Min Liu, MD, (+86)18121150256, liumindr@shphc.org.cn

    Recruiting

  • The Third Hospital of Qinhuangdao

    Qinhuangdao, Hebei

    Lihua Cao, MD, (+86)13091372777, clh2777@163.com

    Shouyun Wang, MD, (+86)18503377689, wsy651126@163.com

    Recruiting

  • Pingdingshan Hospital of Chongqing Public Health Medical Treatment Center

    Shapingba, Chongqing Municipality

    Yangsu Tu, MD, (+86)15923527967, tys302@163.com

    Yuqing Wang, MD

    Recruiting

  • Shengjing Hospital of China Medical University

    Shenyang, Liaoning

    Qiuju Sheng, MD, (+86)18940254812, qq_agnes@163.com

    Xiaoguang Dou, MD, (+86)18940251121, guang40@163.com

    Recruiting

  • The Seventh Affiliated Hospital, Sun Yat-sen University

    Shenzhen, Guangdong

    Bei-Bei Zhu, MD, (+86)15521151504, 991713026@qq.com

    Sai-Nan Pi, Ph.D, (+86)15521212458, sainan.pi@qq.com

    Recruiting

  • Yuyao People's Hospital of Zhejiang Province

    Yuyao, Zhejiang

    Lou Jian Jun, MD, (+86)15888019891

    Yu Hai Yun, MD, (+86)13505786411

    Recruiting

Other trials in China

About this study

Official title: Real World Study of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate to Prevent Vertical Transmission of Hepatitis B in Mothers With High Viral Load

Immunoprophylaxis failure of hepatitis B (HBV) remains a concern and has been reported in approximately 10-30% of infants born to highly viremic mothers with HBeAg-positive. Maternal HBV DNA >6log10 copies/mL (or 200,000 IU/mL) is the major independent risk for mother-to-child transmission (MTCT). 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 when compared 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) with few adverse effects. TAF however, has a better safety profile with less adverse effects to bone mineral density and renal function. The present prospective, double-arm study is to evaluate the non-inferiority in the efficacy and safety of TAF therapy versus TDF therapy in highly viremic mothers and their infants for the prevention of MTCT in the real world setting.

Read the detailed description

This is a prospective, double-arm, multi-center study conducted through 11 centers across China. Consecutive 450 mothers who are eligible for the study will be enrolled during gestational weeks 24-28 to receive TDF or TAF based on the patients' preference, and the treatment will be discontinued right after the delivery. All infants will receive HBV vaccination plus HBIg within 12 hours after birth and the additional HBV vaccination at the age of 4 weeks and 24 weeks. Primary outcome assessment will be performed at the infants' age of 28 will be collected to evaluate non-inferiority in the safety and efficacy of TAF therapy versus TDF therapy. These parameters will be extracted from test results of serum biochemistries, hematology, and virology, including but not limited to aspartate aminotransferase (AST), ALT, HBV DNA levels, and serological status of HBV (HBsAg, HBeAb, HBcAb, HBeAg, and HBsAg).

All aforementioned clinical parameters will be extracted from mothers at the following timepoints for assessment: the baseline, i.e. the start of TAF/TDF treatment, gestational weeks 28, 32, 36, on delivery, and at postpartum weeks 24-28. For the infant, information from two timepoints, at birth and at infant age of 28 weeks, will be collected. This information regarding the infant will include the physical parameters weight, height, head circumference, HBV DNA levels, HBV serological status, if they received hepatitis B immunoglobin (HBIg), if they received the complete series of HBV vaccine. All relevant information regarding the patient will be logged into a password-protected computer for primary and secondary analysis.

Group A: 225 participating mothers will receive TAF (oral 25 mg tablet daily) starting at gestational week 24-28 of pregnancy and continue until delivery. The mothers will be followed together with their infants until postpartum week 28.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. Group B: 225 participating mothers will receive TDF (oral 300 mg tablet daily) starting at gestational week 24-28 of pregnancy and continue until delivery. Patients in group B will have similar follow-up schedules as those in the Group A. 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.

Being tested
Tenofovir Alafenamide 25 MG for arm (A), Tenofovir Disoproxil Fumarate 300mg for arm (B)
Keywords
Chronic Hepatitis B, Pregnancy, Mother to Child Transmission, Vertical Transmission
Medical subject headings
Hepatitis B, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tenofovir Alafenamide 25 MG for arm (A)Drug

    Also called HBIg 200 IU im for infants, HBV vaccine 10 ug im for infants

    Tenofovir Alafenamide (TAF) will be provided, 25 mg Per Oral daily.

  • Tenofovir Disoproxil Fumarate 300mg for arm (B)Drug

    Also called HBIg 200 IU im for infants, HBV vaccine 10 ug im for infants

    Tenofovir Disoproxil Fumarate (TDF) will be provided, 300 mg Per Oral daily.

Study groups in NCT04211805
Study groupRoleWhat they receive
Arm (A) TAF Group Comprised of Patients from 11 Centers.225 consecutive patients will be treated with local standard of care. The antiviral drug Tenofovir Alafenamide (TAF) will be used to treat highly viremic chronic hepatitis B mothers from the gestational week 24-28 of pregnancy to delivery of infant at eleven centers across the People's Republic of China (PRC). 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.
Receives: Drug: Tenofovir Alafenamide 25 MG for arm (A)
Arm (B) TDF Group Comprised of Patients from 11 Centers.225 consecutive patients will be treated with local standard of care. The antiviral drug Tenofovir Disoproxil Fumarate (TDF) will be used to treat highly viremic chronic hepatitis B mothers from the gestational week 24-28 of pregnancy to delivery of infant at eleven centers across the People's Republic of China (PRC). 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.
Receives: Drug: Tenofovir Disoproxil Fumarate 300mg for arm (B)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: From the date of birth to the age of 24-28 weeks

  2. Assessment on Congenital Defects and/or Malformation Rates in Each Infant Group for Comparison

    The rate of congenital defects and/or malformation rates in infants. Congenital defects and/or malformation rates are defined as the proportion of infants with the aforementioned abnormalities discovered during the study period. The rate of infant congenital defect/malformation as determined in group A will be compared with that of group B.

    Measured: from the date of birth to Infant's age of 24-28 weeks

Secondary outcomes (9)

  1. Assessment on the change in Maternal HBV DNA Levels at Delivery

    Assess the change in maternal HBV DNA levels (IU/mL) at delivery when compared to the baseline before initiating TAF/TDF.

    Measured: from gestational week 24-28 week to delivery

  2. Maternal Serological Outcomes During the Study: Percentage of Mothers who Loss/Seroconversion of HBsAg or/and HBeAg During the Study

    Assess the percentage of mothers who loss/seroconversion of HBsAg or/and HBeAg during the study. Loss is defined by a test showing a negative HBsAg/HBeAg result at the end of the trial, given a positive respective test result at baseline. A seroconversion is defined as a test showing a negative HBsAg and a positive HBsAb result, or a negative HBeAg and a positive HBeAb result at the end of the trial, given a positive HBsAg/HBeAg test result at baseline. The proportion of mothers who experience loss/seroconversion as determined in group A will be compared with that of group B.

    Measured: from gestational week 24-28 week to postpartum week 28

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

    Assess the percentage of Mothers who have adverse events during the study, graded by the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. The proportion of mothers who experience adverse events as determined in group A will be compared with that of group B.

    Measured: Gestational week 24-28 until Postpartum Week 28

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

    Assess the percentage of infants who have adverse events during the study, graded by the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. The proportion of infants who experience adverse events as determined in group A will be compared with that of group B.

    Measured: Delivery until Infant age Week 28

  5. Percentage of Mothers with Alanine transferase (ALT) Levels Within the Normal Limit

    To calculate the percentage of mothers at postpartum 28 weeks whose ALT (U/L) levels stay within the normal limit in response to therapy. The proportion of mothers whose ALT levels who stay within the normal limit as determined in group A will be compared with that of group B.

    Measured: Gestational week 24-28 until Postpartum week 28

  6. Percentage of Mothers with Aspartamine transferase (AST) Levels Within the Normal Limit

    To calculate the percentage of mothers at postpartum 28 weeks whose AST (U/L) levels stay within the normal limit in response to therapy. The proportion of mothers whose AST levels who stay within the normal limit as determined in group A will be compared with that of group B.

    Measured: Gestational week 24-28 until Postpartum week 28

  7. Group A: Proportion of Infants Born to Mothers Who Received TAF, Whose Physical Growth Characteristics Stay Within the Published National Normal Range.

    Physical growth characteristics of the infants, born to mothers who received TAF, at the time points on birth and infant age of 24-28 weeks will be compared with the normal range of the national database published in recent years and analyzed. The proportion of infants whose growth characteristics are outside the published national range at the end of the study as determined in group A will be compared with that of group B.

    Measured: Delivery to Infant age 28 weeks

  8. Group B: Proportion of Infants Born to Mothers Who Received TDF, Whose Physical Growth Characteristics Stay Within the Published National Normal Range.

    Physical growth characteristics of the infants, born to mothers who received TDF, at the time points on birth and infant age of 24-28 weeks will be compared with the normal range of the national database published in recent years and analyzed.The proportion of infants whose growth characteristics are outside the published national range at the end of the study as determined in group A will be compared with that of group B.

    Measured: Delivery to Infant age 28 weeks

  9. Tolerability of TDF vs TAF Therapy: Percentage of Mothers who Discontinue Therapy Due to the Adverse Event(s) During the Study.

    Assess the percentage of mothers who discontinue therapy due to the adverse event(s) during the study. The proportion of mothers who discontinue therapy as determined in group A will be compared with that of group B.

    Measured: Gestational week 24-28 until Delivery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Dec 2019
  2. Study start27 Jan 2020
  3. Primary completion30 Sep 2021 (estimated)
  4. Study completion30 Sep 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
450 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04211805
Sponsor's protocol ID
CN-P919-2020
Status last verified
Dec 2020
First submitted
6 Dec 2019
Last updated
29 Dec 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Xu WM, Cui YT, Wang L, Yang H, Liang ZQ, Li XM, Zhang SL, Qiao FY, Campbell F, Chang CN, Gardner S, Atkins M. Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study. J Viral Hepat. 2009 Feb;16(2):94-103. doi: 10.1111/j.1365-2893.2008.01056.x. Epub 2008 Oct 8.

    PubMed 19175878

  • Zou H, Chen Y, Duan Z, Zhang H. Protective effect of hepatitis B vaccine combined with two-dose hepatitis B immunoglobulin on infants born to HBsAg-positive mothers. PLoS One. 2011;6(10):e26748. doi: 10.1371/journal.pone.0026748. Epub 2011 Oct 28.

    PubMed 22053208

  • 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.

    PubMed 27305192

  • 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.

    PubMed 29514030

  • Wiseman E, Fraser MA, Holden S, Glass A, Kidson BL, Heron LG, Maley MW, Ayres A, Locarnini SA, Levy MT. Perinatal transmission of hepatitis B virus: an Australian experience. Med J Aust. 2009 May 4;190(9):489-92. doi: 10.5694/j.1326-5377.2009.tb02524.x.

    PubMed 19413519

Questions about this trial

What is this clinical trial studying?

An observational study of Hepatitis B, Chronic and Pregnancy Related, run by New Discovery LLC at 11 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 29 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Harry Huang, BS ((+1)5163048196, harry.huang887@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 the age of 24-28 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04211805, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2020.

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