Hepatitis B, ChronicNCT04237376
Chronic HBV Infection in Pregnant Women Taking TAF to Prevent Vertical Transmission
An observational study of Hepatitis B, Chronic and Pregnancy Related, run by New Discovery LLC at 4 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 to 35 years, women only
- Conditions the study is for
- Hepatitis B, Chronic, Pregnancy Related
- What is being tested?
- Tenofovir Alafenamide 25 MG and Tenofovir Disoproxil Fumarate 300 MG Oral Tablet
- Type of treatment
- Vaccines, Pill or oral medicine
- How many people
- 600 participants
- Where
- 4 sitesChina
- Study dates
- 9 Apr 2019to 30 Sep 2020
- 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 20 to 35 years
- Women only
- No healthy volunteers
- Adult
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.
Who may be able to join
- 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.
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
China4 sites, 4 recruiting
- Recruiting
Beijing You'an Hospital, Capital Medical University
Beijing, Beijing Municipality, 100069
Mengyu Zhao, MD, (+86) 18801123990, m18801123990@163.com
Yu Chen, MD, (+86) 13391663900, chybeyond@163.com
- Recruiting
Department of Infectious Disease,The Fourth Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, 150001
Jian Fan, MD, (+86) 15104669604, yichunxiaoxinganling@126.com
Liying Zhu, MD, (+86) 13199561586, zlyhmu@163.com
- Recruiting
The Third Hospital of Qinhuangdao City
Qinhuangdao, Hebei, 066000
Shouyun Wang, MD, (+86) 18503377689, wsy651126@126.com
Lihua Cao, MD, (+86) 13091372777, clh2777@163.com
- Recruiting
Tongliao Infectious Disease Hospital
Tongliao, Inner Mongolia, 028000
Min Li, MD, +86-15947435532, ixhai@126.com
Baiyila Han, MD, +86-13947517988, hanbaiyila@163.com
About this study
Official title: Chronic HBV Infection in Pregnant Women Taking TAF to Prevent Mother-to-child Transmission in the Third Trimester: a Multicenter, Prospective Study
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.
Read the detailed description
Mother-to-child transmission is the main route of transmission of HBV in China, and about 30% - 50% of chronic HBV carriers are infected by this route. Although the current hepatitis B vaccine combined with hepatitis B immunoglobulin scheme has achieved excellent results, about 5% - 10% of transmission prevention failure still occur. More than 90% of newborns will develop chronic infection after HBV infection, and about one quarter will eventually develop cirrhosis and / or hepatocellular carcinoma, which is extremely serious. Therefore, improving and optimizing the current transmission prevention technology and program to further increase the success rate of HBV mother-to-child prevention is to reduce the transmission and prevalence of HBV in China, reduce the burden of hepatitis B disease, and achieve the "three-year plan" and "two rates" goals.
Currently, pregnant women's blood hepatitis B virus load ≥ 2 × 10^5 IU/mL before delivery is the main risk factor that affects transmission prevention and whether infant infection occurs. For pregnant women with high HBV viral load, antiviral therapy during pregnancy can further reduce mother-to-child transmission of HBV. Previous studies have confirmed that tenofovir disoproxil fumarate (TDF) 300mg as a single therapy or combination therapy has good safety and antiviral activity, and can be used as a high viral load for chronic HBV infection as a first-line antiviral treatment for pregnant women. Tenofovir alafenamide (TAF) is a first-line treatment for chronic hepatitis B. Its specification is 25mg. It is an RNA-dependent DNA polymerase inhibitor. The agent is an oral prodrug of tenofovir (TFV), similar to TDF. Because the dosage is much lower than TDF, the incidence of adverse reactions is significantly lower than TDF, but the clinical efficacy is equivalent to TDF. Studies have reported that TAF treatment of HBeAg-positive chronic hepatitis B patients, at 96 weeks HBsAg and HBeAg negative rate, serological conversion rate, ALT normalization rate, etc. were not statistically different from the TDF treatment group. The incidence of ≥ 5% reduction in hip bone and spine bone density, as well as ≥ 5% decrease in estimated glomerular filtration rate (eGFR) from baseline were significantly lower than those in the TDF treatment group. TAF is recommended as the drug of choice for the treatment of chronic hepatitis B.
Extensive past data on pregnant women (over 3,000 exposure outcomes) have shown that there are no malformations or fetal / newborn toxicity associated with TDF. However, no such data exists for TAF. Presently, TAF has been approved by the State Food and Drug Administration (SFDA) and marketed in China in December 2018. SFDA Label has suggested that TAF may be considered during pregnancy if necessary. It has not been reported whether the application of TAF in pregnant women can achieve better effects and safety of mother-to-child transmission prevention, and is the focus of this current study.
This is a multicenter, prospective, triple arm cohort study from the gestational age of 28 weeks in pregnancy to post-partum week 28. The enrollment from 4 centers (Beijing You'an Hospital, Capital Medical University, the Fourth Affiliated Hospital of Harbin Medical University, the third hospital of Qinhuangdao city, Inner Mongolia Tongliao infectious disease hospital) will be caped for sample balance. Consecutive 120 HBeAg-positive and HBV DNA levels ≥ 2 × 10^6 IU/mL pregnant women will be enrolled to receive TAF (25mg oral daily) treatment from the aforementioned 4 centers, consecutive 120 HBeAg-positive and HBV DNA levels ≥ 2 × 10^6 IU/mL pregnant women will be enrolled to receive TDF (300mg oral daily) treatment, and a historical cohort of consecutive highly viremic mothers with HBV DNA levels ≥ 2 × 10^6 IU/mL will be retrospective enrolled as the control group. Patients in the TAF-treated group will receive TAF starting at week 28 of gestation until delivery (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). All infants will receive passive-active immunoprophylaxis. According to the mother's wishes, the mother's milk is collected every day for 5-7 days for TAF concentration determination. In this trial, when the creatinine clearance is less than 15 mL/min, the subjects will discontinue the drug permanently. Subjects with permanent discontinuation (either before or after discontinuation according to the protocol) were followed up every 4 weeks until 16 weeks after discontinuation, or until they received new antiviral treatment. The primary endpoint was the rate of mother-to-child transmission in TAF-treated group compared with control group. The tolerance and safety in TAF-treated group, including congenital malformation rate of infants. The secondary efficacy endpoint was the decrease of HBV DNA level at delivery, the clearance and seroconversion rate of HBsAg or / and HBeAg, ALT normalization and other adverse events of mothers and infants.
For comparison, there will be two comparative arms of mothers whose pregnancies were followed at a single center, Capital Medical University, Beijing Youan Hospital. Arm B will consist of 120 consecutive HBeAg-positive and HBV DNA levels ≥ 2 × 10^6 IU/mL pregnant women enrolled to receive TDF (300mg oral daily) treatment, with all treatment variables constant with the TAF treatment group to act as a control. The TDF treatment for arm B will start at week 28 of gestation until delivery. Arm C will consist of 360 HBeAg-positive and HBV DNA levels ≥ 2 × 10^6 IU/mL pregnant women that did not receive any antiviral treatment during pregnancy. This third group is a historical cohort that will be retrospectively enrolled as an additional comparative arm for further comparison and analysis.
- Conditions
- Hepatitis B, Chronic, Pregnancy Related
- Being tested
- Tenofovir Alafenamide 25 MG, Tenofovir Disoproxil Fumarate 300 MG Oral Tablet
- 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 MGDrug
Also called Vemlidy
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.
Tenofovir Disoproxil Fumarate 300 MG Oral TabletDrug
Also called Viread
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Tenofovir Disoproxil Fumarate 300 MG Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
Assess the percentage of mothers experiencing reduction of maternal HBV DNA levels (IU/mL) > 20,000 IU/mL at delivery when compared to the baseline before initiating TAF/TDF. The proportion of mothers who experience a reduction of maternal HBV DNA levels (IU/mL) > 20,000 IU/mL at delivery as determined in all respective groups will be compared.
Measured: At delivery
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 all respective groups will be compared.
Measured: 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
ssess 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 all respective groups will be compared.
Measured: Gestational week 24-28 until Postpartum Week 28
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 all respective groups will be compared.
Measured: At birth until Infant age Week 28
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 all respective groups will be compared.
Measured: Gestational week 24-28 until Postpartum week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2020
- Study start9 Apr 2019
- Primary completion30 Sep 2020 (estimated)
- Study completion30 Sep 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New Discovery LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Zhongping Duan, MD, Principal investigator, Capital Medical University, Beijing You'an HospitalCalvin Q Pan, MD, Study chair, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04237376
- Sponsor's protocol ID
- 2017ZX10201201-001
- Status last verified
- Jan 2020
- First submitted
- 21 Dec 2019
- Last updated
- 23 Jan 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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 29514030Pan 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 27305192Chen 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.
PubMed 25851052Chan 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.
PubMed 28404091Buti 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.
PubMed 28404092Zou 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.
PubMed 39953819
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chronic HBV Infection in Pregnant Women Taking TAF to Prevent Mother-to-child Transmission in the Third Trimester: a Multicenter, Prospective Study
- ClinicalTrials.gov ID
- NCT04237376
- Acronym / sponsor ID
- 2017ZX10201201-001
- Conditions
- Hepatitis B, Chronic, Pregnancy Related
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- New Discovery LLCIndustry (pharma, biotech, devices)
- Study start
- 9 Apr 2019 (actual)
- Primary completion
- 30 Sep 2020 (estimated)
- Study completion
- 30 Sep 2020 (estimated)
- First posted
- 23 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Mother-to-child transmission is the main route of transmission of HBV in China, and about 30% - 50% of chronic HBV carriers are infected by this route. Although the current hepatitis B vaccine combined with hepatitis B immunoglobulin scheme has achieved excellent results, about 5% - 10% of transmission prevention failure still occur. More than 90% of newborns will develop chronic infection after HBV infection, and about one quarter will eventually develop cirrhosis and / or hepatocellular carcinoma, which is extremely serious. Therefore, improving and optimizing the current transmission prevention technology and program to further increase the success rate of HBV mother-to-child prevention is to reduce the transmission and prevalence of HBV in China, reduce the burden of hepatitis B disease, and achieve the "three-year plan" and "two rates" goals.
Currently, pregnant women's blood hepatitis B virus load ≥ 2 × 10^5 IU/mL before delivery is the main risk factor that affects transmission prevention and whether infant infection occurs. For pregnant women with high HBV viral load, antiviral therapy during pregnancy can further reduce mother-to-child transmission of HBV. Previous studies have confirmed that tenofovir disoproxil fumarate (TDF) 300mg as a single therapy or combination therapy has good safety and antiviral activity, and can be used as a high viral load for chronic HBV infection as a first-line antiviral treatment for pregnant women. Tenofovir alafenamide (TAF) is a first-line treatment for chronic hepatitis B. Its specification is 25mg. It is an RNA-dependent DNA polymerase inhibitor. The agent is an oral prodrug of tenofovir (TFV), similar to TDF. Because the dosage is much lower than TDF, the incidence of adverse reactions is significantly lower than TDF, but the clinical efficacy is equivalent to TDF. Studies have reported that TAF treatment of HBeAg-positive chronic hepatitis B patients, at 96 weeks HBsAg and HBeAg negative rate, serological conversion rate, ALT normalization rate, etc. were not statistically different from the TDF treatment group. The incidence of ≥ 5% reduction in hip bone and spine bone density, as well as ≥ 5% decrease in estimated glomerular filtration rate (eGFR) from baseline were significantly lower than those in the TDF treatment group. TAF is recommended as the drug of choice for the treatment of chronic hepatitis B.
Extensive past data on pregnant women (over 3,000 exposure outcomes) have shown that there are no malformations or fetal / newborn toxicity associated with TDF. However, no such data exists for TAF. Presently, TAF has been approved by the State Food and Drug Administration (SFDA) and marketed in China in December 2018. SFDA Label has suggested that TAF may be considered during pregnancy if necessary. It has not been reported whether the application of TAF in pregnant women can achieve better effects and safety of mother-to-child transmission prevention, and is the focus of this current study.
This is a multicenter, prospective, triple arm cohort study from the gestational age of 28 weeks in pregnancy to post-partum week 28. The enrollment from 4 centers (Beijing You'an Hospital, Capital Medical University, the Fourth Affiliated Hospital of Harbin Medical University, the third hospital of Qinhuangdao city, Inner Mongolia Tongliao infectious disease hospital) will be caped for sample balance. Consecutive 120 HBeAg-positive and HBV DNA levels ≥ 2 × 10^6 IU/mL pregnant women will be enrolled to receive TAF (25mg oral daily) treatment from the aforementioned 4 centers, consecutive 120 HBeAg-positive and HBV DNA levels ≥ 2 × 10^6 IU/mL pregnant women will be enrolled to receive TDF (300mg oral daily) treatment, and a historical cohort of consecutive highly viremic mothers with HBV DNA levels ≥ 2 × 10^6 IU/mL will be retrospective enrolled as the control group. Patients in the TAF-treated group will receive TAF starting at week 28 of gestation until delivery (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). All infants will receive passive-active immunoprophylaxis. According to the mother's wishes, the mother's milk is collected every day for 5-7 days for TAF concentration determination. In this trial, when the creatinine clearance is less than 15 mL/min, the subjects will discontinue the drug permanently. Subjects with permanent discontinuation (either before or after discontinuation according to the protocol) were followed up every 4 weeks until 16 weeks after discontinuation, or until they received new antiviral treatment. The primary endpoint was the rate of mother-to-child transmission in TAF-treated group compared with control group. The tolerance and safety in TAF-treated group, including congenital malformation rate of infants. The secondary efficacy endpoint was the decrease of HBV DNA level at delivery, the clearance and seroconversion rate of HBsAg or / and HBeAg, ALT normalization and other adverse events of mothers and infants.
For comparison, there will be two comparative arms of mothers whose pregnancies were followed at a single center, Capital Medical University, Beijing Youan Hospital. Arm B will consist of 120 consecutive HBeAg-positive and HBV DNA levels ≥ 2 × 10^6 IU/mL pregnant women enrolled to receive TDF (300mg oral daily) treatment, with all treatment variables constant with the TAF treatment group to act as a control. The TDF treatment for arm B will start at week 28 of gestation until delivery. Arm C will consist of 360 HBeAg-positive and HBV DNA levels ≥ 2 × 10^6 IU/mL pregnant women that did not receive any antiviral treatment during pregnancy. This third group is a historical cohort that will be retrospectively enrolled as an additional comparative arm for further comparison and analysis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm A: CHB Mothers treated with TAF during Pregnancy | – | Drug: Tenofovir Alafenamide 25 MG120 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. |
| 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 | – | Drug: Tenofovir Disoproxil Fumarate 300 MG Oral TabletThis 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. |
Who may qualify
- Ages
- 20 to 35 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir Alafenamide 25 MGAlso: VemlidyTenofovir 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. | Drug | Treatment Arm A: CHB Mothers treated with TAF during Pregnancy |
| Tenofovir Disoproxil Fumarate 300 MG Oral TabletAlso: VireadTenofovir 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. | Drug | Comparative Arm B: CHB Pregnant Mothers treated with TDF |
Primary outcome
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
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.
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. The proportion of infants who experience congenital defects and/or malformation as determined in all respective groups will be compared.
Tolerability of TDF/TAF therapy: Percentage of mothers who discontinue on TDF/TAF therapy due to the adverse event(s) during the study
Time frame: Gestational week 28 through delivery of their infant, on average at gestational week 36.
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.
5 secondary outcomes
Assessment on the reduction of maternal HBV DNA levels at delivery
Time frame: At delivery
Maternal serological outcomes during the study: Percentage of mothers who loss/seroconversion of HBsAg or/and HBeAg during the study
Time frame: 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
Time frame: Gestational week 24-28 until Postpartum Week 28
Incidence of Treatment-Emergent Adverse Events in Infants as Stratified by the CTCAE v 5.0
Time frame: At birth until Infant age Week 28
Percentage of Mothers with Alanine transferase (ALT) levels within the normal limit
Time frame: Gestational week 24-28 until Postpartum week 28
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2020.
- Background: PubMed 29514030Jourdain 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.
- Background: PubMed 27305192Pan 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.
- Background: PubMed 25851052Chen 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.
- Background: PubMed 28404091Chan 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.
- Background: PubMed 28404092Buti 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.
- Derived from this study: PubMed 39953819Zou 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhongping Duan, MD principal investigator
Capital Medical University, Beijing You'an Hospital
Calvin Q Pan, MD study chair
NYU Langone Health
4 sites in 1 country: see every site and its status.
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 4 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 6 inclusion and 15 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 23 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 Huaibin Zou, MD (+86-13720084736, zhbin03@126.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 3 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 NCT04237376, which also lists 6 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 23 Jan 2020.