The Effectiveness and Safety of Tenofovir Alafenamide in the Treatment of Chronic Hepatitis B Patients With Mildly Elevated Alanine Aminotransferase and Significant Liver Injury.
NCT ID: NCT04674423
Last Updated: 2020-12-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE4
40 participants
INTERVENTIONAL
2020-05-14
2025-12-31
Brief Summary
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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
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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.
2. 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
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Keywords
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Treatment groups:
1. TAF treatment group (144 weeks)
2. Controlled group (144 weeks)
Study Groups
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TAF Treatment
TAF treatment for 144 weeks and followed for 48 weeks after 144-week TAF treatment
Tenofovir Alafenamide
Tenofovir Alafenamide treatment for 144 weeks
Observation arm
Observation for 144 weeks
No interventions assigned to this group
Interventions
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Tenofovir Alafenamide
Tenofovir Alafenamide treatment for 144 weeks
Eligibility Criteria
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Inclusion Criteria
* 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;
Exclusion Criteria
* 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.
* 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.
20 Years
ALL
No
Sponsors
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National Cheng-Kung University Hospital
OTHER
Responsible Party
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Locations
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National Cheng-Kung University Hospital
Tainan City, , Taiwan
Countries
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Central Contacts
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Facility Contacts
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Pin-Nan Cheng, PhD
Role: primary
Li-Chen Lin
Role: backup
Other Identifiers
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AB-CR 108-062
Identifier Type: -
Identifier Source: org_study_id