Hepatitis B InfectionPhase 4NCT01488526
Tenofovir in Late Pregnancy to Prevent Vertical Transmission of Hepatitis B Virus
A Phase 4 study testing TDF treatment in people with Hepatitis B Infection and Chronic Infection, run by New Discovery LLC at 5 sites in China.
Trial summary
Immunoprophylaxis failure of hepatitis B virus (HBV) leading to vertical transmission remains a concern and has been reported in approximately 8-15% of infants born to hepatitis B e antigen (HBeAg) positive mothers with high levels of HBV DNA. Read more about this study
- Who is it for?
- Ages 20 to 35 years, women only
- Conditions the study is for
- Hepatitis B Infection, Chronic Infection, Viremia
- What is being tested?
- TDF treatment
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 5 sitesChina
- Study dates
- 1 Mar 2012to 28 Jun 2018
- Phase
- Phase 4
- 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
Who may be able to join
- documented CHB infection with HBsAg positive > 6 months
- HBeAg+ CHB pregnant women
- gestational age between 30-32 weeks
- HBV DNA > 6 log10 copies/mL (or >200,000 IU/mL)
- both mother and father of the child are willing to consent for the study
- Major Exclusion Criteria:
Show all 17Show fewer
- co-infection with hepatitis A, C, D, E, HIV-1 or sexually transmitted disease (STD)
- decompensated liver disease or significant co-morbidity
- history of abortion, or diagnosis of fetal defect, or congenital malformation in prior pregnancy
- antiviral used within six months prior to this pregnancy, or history of renal or tubular function impairment due to adefovir.
- requirement for other medication during pregnancy to manage other chronic disease(s) or concurrent treatment with immune-modulators, cytotoxic drugs, or steroids
- the biological father of the child had CHB
- clinical signs of threatened miscarriage in early pregnancy
- evidence of hepatocellular carcinoma
- maternal alanine aminotransferase (ALT) > or = 5 x upper limit of normal (U/mL), or Total Bilirubin > or = 2, or glomerular filtration rate (GFR) < 100, or Albumin < 25 g/L
- evidence of fetal deformity by ultrasound examination
- patient is participating other clinical study
Who cannot join
None listed.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites
Hepatobiliary Disease Hospital of Jilin Province
Changchun, Jilin, 130062
Southwest Hospital
Chongqing, Chongqing Municipality, 400038
The Second Affiliated Hospital of the Southeast University
Nanjing, Jiangsu, 210003
Nanyang Central Hospital
Nanyang, Henan, 473000
The Fifth Hospital of Shijiazhuang
Shijiazhuang, Hebei, 050021
About this study
Official title: Tenofovir Disoproxil Fumarate in Late Pregnancy to Prevent Vertical Transmission of Hepatitis B Virus in Highly Viremic Mothers
Immunoprophylaxis failure of hepatitis B virus (HBV) leading to vertical transmission remains a concern and has been reported in approximately 8-15% of infants born to hepatitis B e antigen (HBeAg) positive mothers with high levels of HBV DNA. Maternal HBV DNA > 6log10 copies/mL (or >200,000 IU/mL) is the major risk for the mother-to-child transmission. Prior observational studies have shown that antiviral therapy including lamivudine or telbivudine use during late pregnancy can safely reduce the rate of vertical transmission in this special population compared to untreated patients.
Tenofovir Disoproxil (TDF), a pregnancy category B medication, reduces HBV DNA and normalizes serum alanine aminotransferase (ALT) in chronic hepatitis B patients (CHB) with few adverse effects. Two aspects on tenofovir use in pregnancy will be evaluated prospectively in this study:
- The data on its tolerability and safety in HBeAg+ pregnant women with HBV DNA > 6log10 copies/mL (or > 200,000 IU/mL) during late pregnancy and infants.
- Its efficacy in the reduction of HBV vertical transmission rate.
Read the detailed description
Eligible mothers will be randomized (1:1) to either TDF-treated group or untreated group with about 100 subjects in each arm. The treatment group will receive TDF starting at week 30-32 of gestation until week 4 postpartum; follow up will continue until post-partum week 28 and infants age of 28 weeks. Untreated group will receive the standard of care with similar follow-up schedule as the treatment group.
- Conditions
- Hepatitis B Infection, Chronic Infection, Viremia
- Being tested
- TDF treatment
- Keywords
- Hepatitis B, Vertical transmission, Pregnancy, Antiviral treatment
- Medical subject headings
- Hepatitis B, Persistent Infection, Viremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TDF treatmentDrug
Also called Viread, Tenofovir, TDF, Hepatitis B-IgG, Hepatitis B vaccine
About 100 mothers treated with tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum, then observed to the end of the study at post-partum week 28, paired infants received standard HBV prophylaxis.
| Study group | Role | What they receive |
|---|---|---|
| Control arm: HBIG & vaccine for infants | No intervention | Provide standard of care to mothers and standard immunoprophylaxis to their infants |
| TDF treatment arm | Experimental | tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum for mothers and standard immunoprophylaxis to their infants Receives: Drug: TDF treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure the number of infants who have HBV infection at the age of 28 weeks
Measured: From the date of birth to age of 28 weeks
Assessment of the safety and tolerability of TDF, measure the number of participants and paired infants with adverse events
Measured: From the date of randomization until 28 weeks of postpartum.
Secondary outcomes (3)
Measure maternal HBV DNA reduction during the study period when compared to the baseline
Measured: From the date of radomization to the time of delivery (upto 12 weeks from the radomization)
Measure maternal HBV DNA reduction during the study period when compared to the baseline
Measured: From the date of radomization to the time of delivery (about 8 - 10 weeks from the radomization)
percentage of mothers with sero-negativity or sero-conversion of HBsAg and/or HBeAg in each group for comparison
Measured: From the date of randomization until 28 weeks of postpartum.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2011 (estimated)
- Study start1 Mar 2012
- Primary completion28 Apr 2014
- Study completion28 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatitis B InfectionStudies 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- New Discovery LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Gilead Sciences
- Responsible party
- Sponsor
- Investigators
- Calvin Q Pan, MD, Study chair, Leading Principle Investigator, Division of Gastroenterology and Hepatology, NYU Langone Medical Center, New YorkZhongping Duan, MD, Study director, Capital Medical UniversityShuqin Zhang, MD, Principal investigator, Hepatobiliary Disease Hospital of Jilin Province, Jilin, ChinaErhei Dai, MD, Principal investigator, The Fifth Hospital of Shijiazhuang, Shijiazhuang, Hebei, ChinaGuorong Han, MD, Principal investigator, The Second Affiliated Hospital of the Southeast University, Nanjing, ChinaHuaihong Zhang, MD, Principal investigator, Nanyang Central Hospital, Nanyang, Henan, ChinaYuming Wang, MD, Principal investigator, Southwest Hospital, Chongqing, Chongqing, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01488526
- Sponsor's protocol ID
- IN-US 174-0174
- Status last verified
- Dec 2019
- First submitted
- 30 Nov 2011
- Last updated
- 9 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Pan CQ, Dai E, Duan Z, Han G, Zhao W, Wang Y, Zhang H, Zhu B, Jiang H, Zhang S, Zhang X, Zou H, Chen X, Chen Y. Long-term safety of infants from mothers with chronic hepatitis B treated with tenofovir disoproxil in China. Gut. 2022 Apr;71(4):798-806. doi: 10.1136/gutjnl-2020-322719. Epub 2021 Mar 31.
PubMed 33789963Pan 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
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tenofovir Disoproxil Fumarate in Late Pregnancy to Prevent Vertical Transmission of Hepatitis B Virus in Highly Viremic Mothers
- ClinicalTrials.gov ID
- NCT01488526
- Acronym / sponsor ID
- IN-US 174-0174
- Conditions
- Hepatitis B Infection, Chronic Infection, Viremia
- Keywords
- Hepatitis B, Vertical transmission, Pregnancy, Antiviral treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- New Discovery LLCIndustry (pharma, biotech, devices)
- Collaborators
- Gilead Sciences
- Study start
- 1 Mar 2012 (actual)
- Primary completion
- 28 Apr 2014 (actual)
- Study completion
- 28 Jun 2018 (actual)
- First posted
- 8 Dec 2011 (estimated)
- 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.
Immunoprophylaxis failure of hepatitis B virus (HBV) leading to vertical transmission remains a concern and has been reported in approximately 8-15% of infants born to hepatitis B e antigen (HBeAg) positive mothers with high levels of HBV DNA. Maternal HBV DNA > 6log10 copies/mL (or >200,000 IU/mL) is the major risk for the mother-to-child transmission. Prior observational studies have shown that antiviral therapy including lamivudine or telbivudine use during late pregnancy can safely reduce the rate of vertical transmission in this special population compared to untreated patients.
Tenofovir Disoproxil (TDF), a pregnancy category B medication, reduces HBV DNA and normalizes serum alanine aminotransferase (ALT) in chronic hepatitis B patients (CHB) with few adverse effects. Two aspects on tenofovir use in pregnancy will be evaluated prospectively in this study:
- The data on its tolerability and safety in HBeAg+ pregnant women with HBV DNA > 6log10 copies/mL (or > 200,000 IU/mL) during late pregnancy and infants.
- Its efficacy in the reduction of HBV vertical transmission rate.
Detailed description
Eligible mothers will be randomized (1:1) to either TDF-treated group or untreated group with about 100 subjects in each arm. The treatment group will receive TDF starting at week 30-32 of gestation until week 4 postpartum; follow up will continue until post-partum week 28 and infants age of 28 weeks. Untreated group will receive the standard of care with similar follow-up schedule as the treatment group.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control arm: HBIG & vaccine for infants | No intervention | –Provide standard of care to mothers and standard immunoprophylaxis to their infants |
| TDF treatment arm | Experimental | Drug: TDF treatmenttenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum for mothers and standard immunoprophylaxis to their infants |
Who may qualify
- Ages
- 20 to 35 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- documented CHB infection with HBsAg positive > 6 months
- HBeAg+ CHB pregnant women
- gestational age between 30-32 weeks
- HBV DNA > 6 log10 copies/mL (or >200,000 IU/mL)
- both mother and father of the child are willing to consent for the study
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| TDF treatmentAlso: Viread, Tenofovir, TDF, Hepatitis B-IgG, Hepatitis B vaccineAbout 100 mothers treated with tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum, then observed to the end of the study at post-partum week 28, paired infants received standard HBV prophylaxis. | Drug | TDF treatment arm |
Primary outcome
Measure the number of infants who have HBV infection at the age of 28 weeks
Time frame: From the date of birth to age of 28 weeks
Assessment of the safety and tolerability of TDF, measure the number of participants and paired infants with adverse events
Time frame: From the date of randomization until 28 weeks of postpartum.
3 secondary outcomes
Measure maternal HBV DNA reduction during the study period when compared to the baseline
Time frame: From the date of radomization to the time of delivery (upto 12 weeks from the radomization)
Measure maternal HBV DNA reduction during the study period when compared to the baseline
Time frame: From the date of radomization to the time of delivery (about 8 - 10 weeks from the radomization)
percentage of mothers with sero-negativity or sero-conversion of HBsAg and/or HBeAg in each group for comparison
Time frame: From the date of randomization until 28 weeks of postpartum.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2019.
- Derived from this study: PubMed 33789963Pan CQ, Dai E, Duan Z, Han G, Zhao W, Wang Y, Zhang H, Zhu B, Jiang H, Zhang S, Zhang X, Zou H, Chen X, Chen Y. Long-term safety of infants from mothers with chronic hepatitis B treated with tenofovir disoproxil in China. Gut. 2022 Apr;71(4):798-806. doi: 10.1136/gutjnl-2020-322719. Epub 2021 Mar 31.
- Derived from this study: 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.
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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.
Calvin Q Pan, MD study chair
Leading Principle Investigator, Division of Gastroenterology and Hepatology, NYU Langone Medical Center, New York
Zhongping Duan, MD study director
Capital Medical University
Shuqin Zhang, MD principal investigator
Hepatobiliary Disease Hospital of Jilin Province, Jilin, China
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing TDF treatment in people with Hepatitis B Infection and Chronic Infection, run by New Discovery LLC at 5 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 17 inclusion and 0 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: finished, as of the sponsor's last update on 9 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure the number of infants who have HBV infection at the age of 28 weeks (time frame: From the date of birth to age of 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 NCT01488526, which also lists 2 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 9 Dec 2019.