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

NCT ID: NCT04211805

Last Updated: 2020-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Total Enrollment

450 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-01-27

Study Completion Date

2021-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hepatitis B, Chronic Pregnancy Related

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Chronic Hepatitis B Pregnancy Mother to Child Transmission Vertical Transmission

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Tenofovir Alafenamide 25 MG for arm (A)

Intervention Type DRUG

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

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.

Tenofovir Disoproxil Fumarate 300mg for arm (B)

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Tenofovir Alafenamide 25 MG for arm (A)

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

Intervention Type DRUG

Tenofovir Disoproxil Fumarate 300mg for arm (B)

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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

HBIg 200 IU im for infants HBV vaccine 10 ug im for infants HBIg 200 IU im for infants HBV vaccine 10 ug im for infants

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Pregnant female, above 18 years of age and under 40 years of age.
2. Gestational age between 12-14 weeks (The screening on patients can be started at gestational week 12).
3. 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.
4. Detectable maternal serum HBsAg and HBeAg at the screening visit.
5. Maternal serum HBV DNA levels exceeding 200,000 IU/mL by the COBAS Amplicor HBV PCR assay at screening visits.
6. 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.
7. 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.

Exclusion Criteria

Patients will be excluded if they have any one of the following:

1. Creatinine clearance \<100 mL/min (using the Cockcroft-Gault method based on serum creatinine and ideal body weight) or hypo-phosphoremia (below normal range).
2. History of renal events on adefovir or history of resistance to adefovir.
3. 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.
4. History of abortion, or congenital malformation, or child infected with HBV in a prior pregnancy.
5. Biological father of the child (current pregnancy) has CHB.
6. Significant renal, cardiovascular, pulmonary, or neurological disease that may impact the subject's participation in the study as per the opinion of the investigator.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

New Discovery LLC

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Calvin Pan, MD

Role: PRINCIPAL_INVESTIGATOR

Beijing Ditan Hospital, Capital Medical University; NYU Langone Health, NY, USA

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Pingdingshan Hospital of Chongqing Public Health Medical Treatment Center

Shapingba, Chongqing Municipality, China

Site Status RECRUITING

First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

Site Status RECRUITING

The Seventh Affiliated Hospital, Sun Yat-sen University

Shenzhen, Guangdong, China

Site Status RECRUITING

Hainan General Hospital

Haikou, Hainan, China

Site Status RECRUITING

The Third Hospital of Qinhuangdao

Qinhuangdao, Hebei, China

Site Status RECRUITING

The Fourth Hospital of Harbin Medical University

Harbin, Heilonjiang, China

Site Status RECRUITING

Xiangya Hospital, Central South University

Changsha, Hunan, China

Site Status RECRUITING

Ganzhou Fifth People's Hospital

Ganzhou, Jiangxi, China

Site Status RECRUITING

Shengjing Hospital of China Medical University

Shenyang, Liaoning, China

Site Status RECRUITING

Shanghai Public Health Clinical Center, Fudan University

Zhujing, Shanghai Municipality, China

Site Status RECRUITING

Yuyao People's Hospital of Zhejiang Province

Yuyao, Zhejiang, China

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

China

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Harry Huang, BS

Role: CONTACT

Phone: (+1)5163048196

Email: [email protected]

Calvin Q Pan, MD

Role: CONTACT

Phone: (+86)15920560416

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Yangsu Tu, MD

Role: primary

Qi Zheng, MD

Role: primary

Xiao Y Lin, MS

Role: backup

Bei-Bei Zhu, MD

Role: primary

Sai-Nan Pi, Ph.D

Role: backup

Jiao Wang, MD

Role: primary

Furong Xiao, MD

Role: backup

Lihua Cao, MD

Role: primary

Shouyun Wang, MD

Role: backup

Lei Yu, MD

Role: primary

Linying Zhu, MD

Role: backup

Yan Huang, MD

Role: primary

Zebing Huang, MD

Role: backup

Huizhen Hong

Role: primary

Lijuan Long, MD

Role: backup

Qiuju Sheng, MD

Role: primary

Xiaoguang Dou, MD

Role: backup

Min-min Sheng, MD

Role: primary

Min Liu, MD

Role: backup

Lou Jian Jun, MD

Role: primary

Yu Hai Yun, MD

Role: backup

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 19175878 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22053208 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27305192 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29514030 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19413519 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CN-P919-2020

Identifier Type: -

Identifier Source: org_study_id