Chronic Hepatitis BNCT04864366
Efficacy and Safety of TAF for 48 Weeks in HBeAg Positive CHB Patients
An observational study of Chronic Hepatitis B, run by Huashan Hospital at 3 sites in China.
Trial summary
The objective of this clinical study was to observe the changes of HBsAg levels after a sequential 48 weeks-treatment of TAF in ETV experienced CHB patients and to monitor the levels of cytokines such as IFN-λ3, IP-10, IL-12, IL-10, and IL-21. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- Tenofovir Alafenamide 25 MG [Vemlidy]
- Type of treatment
- Pill or oral medicine
- How many people
- 150 participants
- Where
- 3 sitesChina
- Study dates
- 30 Apr 2021to 31 Dec 2023
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: HBeAg-positive men, non-pregnant women and non-lactating women (over 18 years of age) who are infected with HBV alone, treatment naïve or only ETV treatment experienced at least 48 weeks. participate will only receive TAF treatment after informed consent.
Who may be able to join
None listed.
Who cannot join
- Treatment naive patients
- treated with NA or/or αIFN within 1 year
- Pregnant women, lactating women, or women who plan to become pregnant within 2 years
- Co-infection with Hepatitis C, Hepatitis D or HIV;
- Chronic liver diseases with non-HBV etiology (including but not limited to: autoimmune hepatitis, primary biliary cirrhosis, primary cirrhosis cholangitis, hemochromatosis, etc.
- There is evidence of Child-Pugh grade C decompensated liver disease, or moderate to severe ascites, and grade III-IV hepatic encephalopathy
Show all 17Show fewer
- There are symptoms and signs of hepatocellular carcinoma. If screening for alpha-fetoprotein (AFP) <50 ng / mL, imaging examination are not required; but if screening for AFP> 50 ng / mL, imaging examination are required
- current alcohol or drug abuse may affect compliance
- Patients who recieved solid organ or bone marrow transplantation. Liver or kidney transplantation patients can be enrolled
- malignant tumors within 5 years. Patients being evaluated for possible malignant tumors should be excluded
- Study drugs were used within 3 months prior to screening
- Patients who are participating in other clinical trials, or have been treated with the study drugs within 12 weeks before screening
- Inability or unwillingness to provide informed consent or non-compliance with research requirements
- Patients who are unwilling to purchase TAF on their own
- In addition to the above exclusion criteria, patients who meet any of the contraindications listed in the label of the investigational drug product
- ETV treatment experienced patients
- ●Patients who had received IFN and/or other NA (except entecavir) within 1 year Other exclusion criteria were as same as 2-13 of the exclusion criteria for treatment naive patients.
Trial locations and contacts
3 sites in 1 country.
China3 sites
Huashan Hospital Affiliated to Fudan University
Shanghai
Ruijin Hospital Affiliate to Shanghai Jiao Tong University School of Medicine
Shanghai
Shanghai Public Health Clinical Center
Shanghai
About this study
The objective of this clinical study was to observe the changes of HBsAg levels after a sequential 48 weeks-treatment of TAF in ETV experienced CHB patients and to monitor the levels of cytokines such as IFN-λ3, IP-10, IL-12, IL-10, and IL-21.
Read the detailed description
The first-line NAs include entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). All the NAs mentioned above could achieve complete virologic response. NAs mentioned above are sufficient in inhibiting viral replication. However, there may exist difference in long-term prognosis such as HBsAg level decline, resistance development and HCC development. A prospective study performed by our team previously showed that TDF was better than ETV in HBsAg decline. A Korean research showed that TDF therapy was associated with a significantly lower risk of HCC than ETV therapy; the TDF group showed a distinct reduction in HBsAg level after one-year treatment. Also, a Japanese RCT study indicated that the reduction in HBsAg level was significantly greater in the TDF arm than the ETV arm at week 24. The mechanism of HBsAg decline induced by TDF has not been fully elucidated. Patients treated with nucleotide analogues (adefovir, tenofovir) had higher serum IFN-λ3 levels than those treated with nucleoside analogues (lamivudine, entecavir), according to results recently published in Gut. A team from Japan has found that nucleotide analogues inhibit LPS-mediated IL-10 production and induce IL-12p70 and TNF-α production. We speculated that, compared with entecavir, tenofovir could up-regulate IFN-λ3 and reduce the level of HBsAg more significantly.
As known as the second generation of TDF, TAF has a significantly longer half-life than TDF. A phase 3 study displayed that TAF 25 mg was non-inferior to TDF 300 mg in suppressing HBV replication, with a better performance in renal and bone safety. However, there is lack of study evaluating TAF in reducing HBsAg and induces IFN-λ3.The aim of this study was to investigate whether the TAF can achieve a better antiviral therapeutic endpoint, i.e. a greater reduction in HBsAg levels, or even meet the therapeutic expectation of stopping NAS in a larger number of treated patients.
The objective of this clinical study was to observe the changes of HBsAg levels after a sequential 48 weeks-treatment of TAF in ETV experienced CHB patients and to monitor the levels of cytokines such as IFN-λ3, IP-10, IL-12, IL-10, and IL-21.
- Conditions
- Chronic Hepatitis B
- Being tested
- Tenofovir Alafenamide 25 MG [Vemlidy]
- 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 [Vemlidy]Drug
TAF is administered as a 25mg/tablet, taken orally with food once daily, for 48 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Treatment naive patients | 1. HBV DNA> 20000 IU/ml
2. ALT>2×ULN；or ALT>1×ULN，but liver biopsy showed inflammation greater than or equal to G2, or/and liver fibrosis greater than or equal to S2
3. No treatment with NA or/or αIFN within 1 year Receives: Drug: Tenofovir Alafenamide 25 MG [Vemlidy] | |
| ETV treatment experienced patients | 1. ETV treatment for 1 to 2 years before
2. HBsAg>3000IU/mL
3. HBV DNA<20IU/mL
4. ALT<1×ULN
5. No other NA therapy prior to entecavir treatment
6. Patients had a desire to convert to TAF therapy Receives: Drug: Tenofovir Alafenamide 25 MG [Vemlidy] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of serum HBsAg at week 48 from baseline.
evaluate the changes of serum HBsAg level after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
Secondary outcomes (15)
Change of serum HBeAg level from baseline.
evaluate the of changes serum HBeAg level from baseline after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
Change of serum HBcAb level from baseline.
evaluate the of changes serum HBcAb level from baseline after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
propotion of patients who maintened HBV DNA suppression.
evaluate the propotion of patients who maintened HBV DNA suppression after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
propotion of patients who maintened ALT normalization.
evaluate the propotion of patients who maintened ALT normalization after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
Change of renal markers - eGFR from baseline.
evaluate the change of renal markers -eGFR after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
Change of renal markers - serum phosphate from baseline.
evaluate the change of renal markers -serum phosphate after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
Change of renal markers - UPCR from baseline.
evaluate the change of renal markers - UPCR after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
Change of renal markers- UACR from baseline.
evaluate the change of renal markers - UACR after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
Change of renal markers - RBP:Cr from baseline.
evaluate the change of renal markers -RBP:Cr after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
Change of renal markers - β2MG:Cr from baseline.
evaluate the change of renal markers - β2MG:Cr after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
Change of IFN-λ3 from baseline.
evaluate the change of IFN-λ3 after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
Change of IP-10 from baseline.
evaluate the change of IP-10 after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
Change of IL-12 from baseline.
evaluate the change of IL-12 after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
Change of IL-10 from baseline.
evaluate the change of IL-10 after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
Change of IL-21from baseline.
evaluate the change of IL-21 after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
Measured: from baseline to week 48 after TAF treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2021
- Study start30 Apr 2021
- Primary completion27 Oct 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- More trials run by Huashan HospitalThe sponsor's other registered studies.
- 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
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Huashan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jiming Zhang, Huashan Hospital
- Investigators
- Jiming Zhang, M.D., Principal investigator, Huashan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04864366
- Sponsor's protocol ID
- TAF-HBeAg-CHB
- Status last verified
- Mar 2023
- First submitted
- 9 Apr 2021
- Last updated
- 15 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of TAF for 48 Weeks in HBeAg Positive CHB Patients
- ClinicalTrials.gov ID
- NCT04864366
- Acronym / sponsor ID
- TAF-HBeAg-CHB
- Conditions
- Chronic Hepatitis B
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Huashan HospitalUniversity, hospital or other
- Study start
- 30 Apr 2021 (actual)
- Primary completion
- 27 Oct 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 28 Apr 2021 (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.
The objective of this clinical study was to observe the changes of HBsAg levels after a sequential 48 weeks-treatment of TAF in ETV experienced CHB patients and to monitor the levels of cytokines such as IFN-λ3, IP-10, IL-12, IL-10, and IL-21.
Detailed description
The first-line NAs include entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). All the NAs mentioned above could achieve complete virologic response. NAs mentioned above are sufficient in inhibiting viral replication. However, there may exist difference in long-term prognosis such as HBsAg level decline, resistance development and HCC development. A prospective study performed by our team previously showed that TDF was better than ETV in HBsAg decline. A Korean research showed that TDF therapy was associated with a significantly lower risk of HCC than ETV therapy; the TDF group showed a distinct reduction in HBsAg level after one-year treatment. Also, a Japanese RCT study indicated that the reduction in HBsAg level was significantly greater in the TDF arm than the ETV arm at week 24. The mechanism of HBsAg decline induced by TDF has not been fully elucidated. Patients treated with nucleotide analogues (adefovir, tenofovir) had higher serum IFN-λ3 levels than those treated with nucleoside analogues (lamivudine, entecavir), according to results recently published in Gut. A team from Japan has found that nucleotide analogues inhibit LPS-mediated IL-10 production and induce IL-12p70 and TNF-α production. We speculated that, compared with entecavir, tenofovir could up-regulate IFN-λ3 and reduce the level of HBsAg more significantly.
As known as the second generation of TDF, TAF has a significantly longer half-life than TDF. A phase 3 study displayed that TAF 25 mg was non-inferior to TDF 300 mg in suppressing HBV replication, with a better performance in renal and bone safety. However, there is lack of study evaluating TAF in reducing HBsAg and induces IFN-λ3.The aim of this study was to investigate whether the TAF can achieve a better antiviral therapeutic endpoint, i.e. a greater reduction in HBsAg levels, or even meet the therapeutic expectation of stopping NAS in a larger number of treated patients.
The objective of this clinical study was to observe the changes of HBsAg levels after a sequential 48 weeks-treatment of TAF in ETV experienced CHB patients and to monitor the levels of cytokines such as IFN-λ3, IP-10, IL-12, IL-10, and IL-21.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment naive patients | – | Drug: Tenofovir Alafenamide 25 MG [Vemlidy]1. HBV DNA> 20000 IU/ml 2. ALT>2×ULN；or ALT>1×ULN，but liver biopsy showed inflammation greater than or equal to G2, or/and liver fibrosis greater than or equal to S2 3. No treatment with NA or/or αIFN within 1 year |
| ETV treatment experienced patients | – | Drug: Tenofovir Alafenamide 25 MG [Vemlidy]1. ETV treatment for 1 to 2 years before 2. HBsAg>3000IU/mL 3. HBV DNA<20IU/mL 4. ALT<1×ULN 5. No other NA therapy prior to entecavir treatment 6. Patients had a desire to convert to TAF therapy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HBeAg-positive men, non-pregnant women and non-lactating women (over 18 years of age) who are infected with HBV alone, treatment naïve or only ETV treatment experienced at least 48 weeks. participate will only receive TAF treatment after informed consent.
Key inclusion criteria (0 listed)
Key exclusion criteria (17 listed)
- Treatment naive patients
- treated with NA or/or αIFN within 1 year
- Pregnant women, lactating women, or women who plan to become pregnant within 2 years
- Co-infection with Hepatitis C, Hepatitis D or HIV;
- Chronic liver diseases with non-HBV etiology (including but not limited to: autoimmune hepatitis, primary biliary cirrhosis, primary cirrhosis cholangitis, hemochromatosis, etc.
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 MG [Vemlidy]TAF is administered as a 25mg/tablet, taken orally with food once daily, for 48 weeks. | Drug | ETV treatment experienced patients, Treatment naive patients |
Primary outcome
Change of serum HBsAg at week 48 from baseline.
Time frame: from baseline to week 48 after TAF treatment
evaluate the changes of serum HBsAg level after 48 week-treatment of TAF in TN and ETV experienced CHB patients.
15 secondary outcomes
Change of serum HBeAg level from baseline.
Time frame: from baseline to week 48 after TAF treatment
Change of serum HBcAb level from baseline.
Time frame: from baseline to week 48 after TAF treatment
propotion of patients who maintened HBV DNA suppression.
Time frame: from baseline to week 48 after TAF treatment
propotion of patients who maintened ALT normalization.
Time frame: from baseline to week 48 after TAF treatment
Change of renal markers - eGFR from baseline.
Time frame: from baseline to week 48 after TAF treatment
Change of renal markers - serum phosphate from baseline.
Time frame: from baseline to week 48 after TAF treatment
Change of renal markers - UPCR from baseline.
Time frame: from baseline to week 48 after TAF treatment
Change of renal markers- UACR from baseline.
Time frame: from baseline to week 48 after TAF treatment
Change of renal markers - RBP:Cr from baseline.
Time frame: from baseline to week 48 after TAF treatment
Change of renal markers - β2MG:Cr from baseline.
Time frame: from baseline to week 48 after TAF treatment
Change of IFN-λ3 from baseline.
Time frame: from baseline to week 48 after TAF treatment
Change of IP-10 from baseline.
Time frame: from baseline to week 48 after TAF treatment
Change of IL-12 from baseline.
Time frame: from baseline to week 48 after TAF treatment
Change of IL-10 from baseline.
Time frame: from baseline to week 48 after TAF treatment
Change of IL-21from baseline.
Time frame: from baseline to week 48 after TAF treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2023.
Related trials for Chronic Hepatitis B
Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B
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.
Jiming Zhang, M.D. principal investigator
Huashan Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Hepatitis B, run by Huashan Hospital at 3 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 0 inclusion and 17 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 15 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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?
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?
Change of serum HBsAg at week 48 from baseline. (time frame: from baseline to week 48 after TAF treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Mar 2023.