Chronic Hepatitis bPhase 4NCT04674423
The Effectiveness and Safety of Tenofovir Alafenamide in the Treatment of Chronic Hepatitis B Patients With Mildly Elevated Alanine Aminotransferase and Significant Liver Injury.
A Phase 4 study testing Tenofovir Alafenamide in people with Chronic Hepatitis b, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
Trial summary
In Taiwan, non-cirrhosis CHB patients with mildly elevated ALT are not candidates for antiviral treatment under Taiwan NIH reimbursement criteria. Disease severity could range from mildly liver injury to cirrhosis in this group of patients. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Chronic Hepatitis b
- What is being tested?
- Tenofovir Alafenamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteTaiwan
- Study dates
- 14 May 2020to 31 Dec 2025
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age more than 20 years
- Presence of HBsAg positivity for more than 6 months that indicated chronic HBV infection;
- HBV viral load more than 20000 IU/mL in HBeAg positive or more than 2000 IU/mL in HBeAg Negative CHB patients;
- Presence of liver injury which was defined as histology activity index (HAI) >3 by Knodell necroinflammantion scoring system or liver fibrosis stage 2 or stage 3 by Metavir scoring system; Liver histology available for evaluation 6 months before starting screening is also acceptable. This criteria is limited to subjects enrolling TAF treatment group.
- ALT level between 1-2 folds of ULN for at least one occasion in recent 1 year before screening;
- Treatment naïve;
Who cannot join
- Other etiology of chronic hepatitis; Those patients with spontaneous clearance of HCV defined as presence of anti-HCV antibody but undetectable of HCV RNA at least 3 months before enrollment and without history of anti-viral treatment could be included.
- Severe comorbid disorders;
- Uncontrolled diabetes mellitus (HBA1c > 8.5%);
- Current evidence or suspicious of malignancy;
- Diagnosis of liver cirrhosis;
- eGFR < or = 30 ml/min/1.73m2.
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- Any one of following hematology or biochemical or clinical abnormalities:
- Albumin <3.5g/dL, Total Bilirubin >2.5mg/dL, prothrombin time prolongation >4 sec or INR >1.7, platelet count <100 x 103 uL, and history or presence of ascites or hepatic encephalopathy.
- Child-bearing age women without the willing to contraceptive control, or lactating or pregnant women.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
National Cheng-Kung University Hospital
Tainan, 704
Pin-Nan Cheng, PhD, +886-972401223, pncheng@mail.ncku.edu.tw
Li-Chen Lin, +886-910819731, lichenlin516@gmail.com
About this study
Official title: The Effectiveness and Safety of Tenofovir Alafenamide in the Treatment of Chronic Hepatitis B Patients With Mildly Elevated Alanine Aminotransferase and Significant Liver Injury
In Taiwan, non-cirrhosis CHB patients with mildly elevated ALT are not candidates for antiviral treatment under Taiwan NIH reimbursement criteria. Disease severity could range from mildly liver injury to cirrhosis in this group of patients. There is a substantial population of patients required antiviral treatment, but not fulfill the criteria of reimbursement treatment.
For the 2 phase 3 trials of TAF, the treatment criteria of ALT were more than 2x of ULN and did not included liver biopsy as a pre-treatment assessment. In this study, CHB patient with ALT level of 1-2x ULN and significant liver injury evaluated by liver biopsy is the target study population.
Read the detailed description
- INTRODUCTION 1.1. Overview Hepatitis B virus (HBV) infection could lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Liver diseases and its complications remains one of the leading causes of death in Taiwan. Epidemiology study shows that HBV viral load is positively associated with incidence of cirrhosis and HCC in the long-term follow-up. Several lines of evidence also revealed that effective control of HBV could reduce the risk of liver decompensation and HCC. Currently, treatment of chronic hepatitis B (CHB) includes pegylated interferon (IFN) and nucleoside or nucleotide analogues (NUC). NUC treatment exhibits the advantages of easy, safe, wide ranges of indications, and strong viral suppression when compared with IFN. 1.2. Clinical experience of NUC treatment The first line of NUC treatment currently are entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF). All these drugs are effective in viral suppression, maintain normal aminotransferase, and exhibit long term safety and minimal viral resistance in treatment for HBeAg positive, HBeAg negative, and cirrhosis patients. Fibrosis improvement and cirrhosis reversion could be achieved in a significant proportion of patients treated with 5-year of ETV or TDF. Some safety concern raised. Renal function deterioration and decreased bone mineral density are present in patient with human immunodeficiency virus (HIV) infection and treated with TDF containing regimen. In CHB patients, impairment of renal function occurs in 1-2% of 8-years TDF treatment. There are controversies in relationship between TDF and bone mineral density. The safety issues of long-term TDF treatment, except its high efficacy in viral suppression, still remains and needs to monitor during treatment course. 1.3. Clinical experience of TAF TAF is a new nucleotide analogue. Two phase III trials, study 108 and 110, were designed to compare the efficacy and safety of TAF and TDF in HBeAg positive and HBeAg negative chronic hepatitis B patients. After two years of treatment, similar viral suppression, but more rapid and higher percentages achieved normalization of alanine aminotransferase (ALT) were observed in TAF group. In addition, renal function measured by estimated glomerular filtration rate (eGFR) was maintained in TAF group. In contrast, TDF group exhibited decline of eGFR. Similarly, bone mineral measured by dual-energy x-ray absorptiometry (DEXA) was maintained TAF group, but decreased in TDF group. In EASL practical guideline for management of chronic hepatitis C suggests that patients with age more than 60 years, bone diseases, and renal alterations should select TAF over TDF. 1.4. Current treatment criteria for non-cirrhosis CHB In APASL and AASLD treatment guideline for CHB, both suggested that non-cirrhosis patients with significant viral load and ALT >2x upper limit of normal range (ULN) in either HBeAg positive or HBeAg negative should be treated. The significant viral load is defined as HBV DNA >20000 IU/mL in HBeAg positive and HBV DNA >2000 IU/mL in HBeAg negative. Current reimbursement criteria of Taiwan NIH also follow these conditions. For those non-cirrhotic patients with significant HBV viral load and ALT level between 1-2x of ULN, treatment is not reimbursed under the NIH criteria. However, treatment should be commenced by liver histology severity which is defined as significant liver inflammation or fibrosis according to APASL and AASLD guidelines. 1.5. Rationale of study In Taiwan, non-cirrhosis CHB patients with mildly elevated ALT are not candidates for antiviral treatment under Taiwan NIH reimbursement criteria. Disease severity could range from mildly liver injury to cirrhosis in this group of patients. There is a substantial population of patients required antiviral treatment, but not fulfill the criteria of reimbursement treatment. For the 2 phase 3 trials of TAF, the treatment criteria of ALT were more than 2x of ULN and did not included liver biopsy as a pre-treatment assessment. In this study, CHB patient with ALT level of 1-2x ULN and significant liver injury evaluated by liver biopsy is the target study population.
- STUDY DESIGN 2.1. Study population This is a phase 4, multicenter, open label study at 12 academic hospitals in Taiwan. Treatment naïve CHB patients with mildly elevated ALT (1-2x of ULN) and significant liver injury evaluated by liver biopsy will be enrolled. The study will be approved by Institutional Review Board (IRB) and will be conducted in accordance with the principles of Declaration of Helsinki and the international Conference on Harmonization for Good Clinical Practice. Informed consent will be provided before enrollment for each patient.
- Conditions
- Chronic Hepatitis b
- Being tested
- Tenofovir Alafenamide
- Keywords
- Chronic hepatitis B, tenofovir Alafenamide, ALT, liver injury
- 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 AlafenamideDrug
Tenofovir Alafenamide treatment for 144 weeks
| Study group | Role | What they receive |
|---|---|---|
| TAF Treatment | Experimental | TAF treatment for 144 weeks and followed for 48 weeks after 144-week TAF treatment Receives: Drug: Tenofovir Alafenamide |
| Observation arm | No intervention | Observation for 144 weeks |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver histological response
Histological response is defined as an improvement of at least two points in the HAI inflammation score of Knodell necro-inflammation scoring system with no worsening of fibrosis or an improvement of at least one point in the fibrosis score of Metavir scoring system.
Measured: Histological response between baseline and after 144-week TAF Treatment
Secondary outcomes (1)
Virology response
Virological response is defined as the percentage of patients achieve HBV DNA lower than lower detection limit.
Measured: Virological response of 1, 2, 3 years of TAF treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2020
- Study start14 May 2020
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (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 National Cheng-Kung University 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cheng-Kung University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04674423
- Sponsor's protocol ID
- AB-CR 108-062
- Status last verified
- Jul 2020
- First submitted
- 14 Dec 2020
- Last updated
- 22 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will be shared after study completion
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effectiveness and Safety of Tenofovir Alafenamide in the Treatment of Chronic Hepatitis B Patients With Mildly Elevated Alanine Aminotransferase and Significant Liver Injury
- ClinicalTrials.gov ID
- NCT04674423
- Acronym / sponsor ID
- AB-CR 108-062
- Conditions
- Chronic Hepatitis b
- Keywords
- Chronic hepatitis B, tenofovir Alafenamide, ALT, liver injury
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- National Cheng-Kung University HospitalUniversity, hospital or other
- Study start
- 14 May 2020 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 19 Dec 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.
In Taiwan, non-cirrhosis CHB patients with mildly elevated ALT are not candidates for antiviral treatment under Taiwan NIH reimbursement criteria. Disease severity could range from mildly liver injury to cirrhosis in this group of patients. There is a substantial population of patients required antiviral treatment, but not fulfill the criteria of reimbursement treatment.
For the 2 phase 3 trials of TAF, the treatment criteria of ALT were more than 2x of ULN and did not included liver biopsy as a pre-treatment assessment. In this study, CHB patient with ALT level of 1-2x ULN and significant liver injury evaluated by liver biopsy is the target study population.
Detailed description
- INTRODUCTION 1.1. Overview Hepatitis B virus (HBV) infection could lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Liver diseases and its complications remains one of the leading causes of death in Taiwan. Epidemiology study shows that HBV viral load is positively associated with incidence of cirrhosis and HCC in the long-term follow-up. Several lines of evidence also revealed that effective control of HBV could reduce the risk of liver decompensation and HCC. Currently, treatment of chronic hepatitis B (CHB) includes pegylated interferon (IFN) and nucleoside or nucleotide analogues (NUC). NUC treatment exhibits the advantages of easy, safe, wide ranges of indications, and strong viral suppression when compared with IFN. 1.2. Clinical experience of NUC treatment The first line of NUC treatment currently are entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF). All these drugs are effective in viral suppression, maintain normal aminotransferase, and exhibit long term safety and minimal viral resistance in treatment for HBeAg positive, HBeAg negative, and cirrhosis patients. Fibrosis improvement and cirrhosis reversion could be achieved in a significant proportion of patients treated with 5-year of ETV or TDF. Some safety concern raised. Renal function deterioration and decreased bone mineral density are present in patient with human immunodeficiency virus (HIV) infection and treated with TDF containing regimen. In CHB patients, impairment of renal function occurs in 1-2% of 8-years TDF treatment. There are controversies in relationship between TDF and bone mineral density. The safety issues of long-term TDF treatment, except its high efficacy in viral suppression, still remains and needs to monitor during treatment course. 1.3. Clinical experience of TAF TAF is a new nucleotide analogue. Two phase III trials, study 108 and 110, were designed to compare the efficacy and safety of TAF and TDF in HBeAg positive and HBeAg negative chronic hepatitis B patients. After two years of treatment, similar viral suppression, but more rapid and higher percentages achieved normalization of alanine aminotransferase (ALT) were observed in TAF group. In addition, renal function measured by estimated glomerular filtration rate (eGFR) was maintained in TAF group. In contrast, TDF group exhibited decline of eGFR. Similarly, bone mineral measured by dual-energy x-ray absorptiometry (DEXA) was maintained TAF group, but decreased in TDF group. In EASL practical guideline for management of chronic hepatitis C suggests that patients with age more than 60 years, bone diseases, and renal alterations should select TAF over TDF. 1.4. Current treatment criteria for non-cirrhosis CHB In APASL and AASLD treatment guideline for CHB, both suggested that non-cirrhosis patients with significant viral load and ALT >2x upper limit of normal range (ULN) in either HBeAg positive or HBeAg negative should be treated. The significant viral load is defined as HBV DNA >20000 IU/mL in HBeAg positive and HBV DNA >2000 IU/mL in HBeAg negative. Current reimbursement criteria of Taiwan NIH also follow these conditions. For those non-cirrhotic patients with significant HBV viral load and ALT level between 1-2x of ULN, treatment is not reimbursed under the NIH criteria. However, treatment should be commenced by liver histology severity which is defined as significant liver inflammation or fibrosis according to APASL and AASLD guidelines. 1.5. Rationale of study In Taiwan, non-cirrhosis CHB patients with mildly elevated ALT are not candidates for antiviral treatment under Taiwan NIH reimbursement criteria. Disease severity could range from mildly liver injury to cirrhosis in this group of patients. There is a substantial population of patients required antiviral treatment, but not fulfill the criteria of reimbursement treatment. For the 2 phase 3 trials of TAF, the treatment criteria of ALT were more than 2x of ULN and did not included liver biopsy as a pre-treatment assessment. In this study, CHB patient with ALT level of 1-2x ULN and significant liver injury evaluated by liver biopsy is the target study population.
- STUDY DESIGN 2.1. Study population This is a phase 4, multicenter, open label study at 12 academic hospitals in Taiwan. Treatment naïve CHB patients with mildly elevated ALT (1-2x of ULN) and significant liver injury evaluated by liver biopsy will be enrolled. The study will be approved by Institutional Review Board (IRB) and will be conducted in accordance with the principles of Declaration of Helsinki and the international Conference on Harmonization for Good Clinical Practice. Informed consent will be provided before enrollment for each patient.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TAF Treatment | Experimental | Drug: Tenofovir AlafenamideTAF treatment for 144 weeks and followed for 48 weeks after 144-week TAF treatment |
| Observation arm | No intervention | –Observation for 144 weeks |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age more than 20 years
- Presence of HBsAg positivity for more than 6 months that indicated chronic HBV infection;
- HBV viral load more than 20000 IU/mL in HBeAg positive or more than 2000 IU/mL in HBeAg Negative CHB patients;
- Presence of liver injury which was defined as histology activity index (HAI) >3 by Knodell necroinflammantion scoring system or liver fibrosis stage 2 or stage 3 by Metavir scoring system; Liver histology available for evaluation 6 months before starting screening is also acceptable. This criteria is limited to subjects enrolling TAF treatment group.
- ALT level between 1-2 folds of ULN for at least one occasion in recent 1 year before screening;
Key exclusion criteria (9 listed)
- Other etiology of chronic hepatitis; Those patients with spontaneous clearance of HCV defined as presence of anti-HCV antibody but undetectable of HCV RNA at least 3 months before enrollment and without history of anti-viral treatment could be included.
- Severe comorbid disorders;
- Uncontrolled diabetes mellitus (HBA1c > 8.5%);
- Current evidence or suspicious of malignancy;
- Diagnosis of liver cirrhosis;
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 AlafenamideTenofovir Alafenamide treatment for 144 weeks | Drug | TAF Treatment |
Primary outcome
Liver histological response
Time frame: Histological response between baseline and after 144-week TAF Treatment
Histological response is defined as an improvement of at least two points in the HAI inflammation score of Knodell necro-inflammation scoring system with no worsening of fibrosis or an improvement of at least one point in the fibrosis score of Metavir scoring system.
1 secondary outcome
Virology response
Time frame: Virological response of 1, 2, 3 years of TAF treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2020.
- Individual participant dataSharing planned: No. IPD will be shared after study completion
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tenofovir Alafenamide in people with Chronic Hepatitis b, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
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 9 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 22 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pin-Nan Cheng, MD (886-6-2353535 ext. 2679, pncheng@mail.ncku.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Liver histological response (time frame: Histological response between baseline and after 144-week 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 22 Dec 2020.