Non-cirrhotic, Chronic Hepatitis BNCT05195450
TAF (Tenofovir Alafenamide) for Preventing Progression of Liver Disease in Non-cirrhotic Chronic HBV Infection With Normal ALT and Low Viral Load.
A study testing Tenofovir alafenamide fumarate in people with Non-cirrhotic, Chronic Hepatitis B, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
Trial summary
The main goal of therapy for patients with chronic HBV infection with no significant liver disease is to improve survival and quality of life by preventing disease progression, development of liver cirrhosis and consequently HCC development. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Non-cirrhotic, Chronic Hepatitis B
- What is being tested?
- Tenofovir alafenamide fumarate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteIndia
- Study dates
- 23 Feb 2022to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
Who may be able to join
- HBsAg+
- Persistent normal ALT 3-6m apart (<30 IU/ml in male and <20 IU/ml in female)
- HBV DNA < 2000 IU/ml
- LSM <8 Kpa
Who cannot join
- Prior NUC/IFN exposure
- Renal dysfunction (Serum Creatinine >1.5 mg/dl)
- Known liver cirrhosis/ esophageal varices
- Any clinical decompensation (CD)
- Pre-existing hepatocellular carcinoma
- Pregnancy
Show all 9Show fewer
- Healthcare workers (HCW)
- Post transplant, patients with advance malignancy or on chemotherapy
- Co-infections - Hepatitis C, Hepatitis D, Human immunodeficiency virus
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
India1 site, 1 recruiting
- Recruiting
Institute of Liver & Biliary Sciences (ILBS)
New Delhi, National Capital Territory of Delhi, 110070
Dr Ankur Jindal, DM, 01146300000, ankur.jindal3@gmail.com
About this study
Official title: TAF (Tenofovir Alafenamide) for Preventing Progression of Liver Disease in Non-cirrhotic Chronic HBV Infection With Normal ALT and Low Viral Load - a Randomized Controlled Trial
The main goal of therapy for patients with chronic HBV infection with no significant liver disease is to improve survival and quality of life by preventing disease progression, development of liver cirrhosis and consequently HCC development. The likelihood of achieving these goals depends on the timing of therapy during the natural course of the infection but also on the stage of the disease and the patients' age when treatment is started. The inhibition of viral replication and normalization of ALT by antiviral treatment has been shown to achieve the elimination of chronic HBV-induced necroinflammatory activity and progressive fibrotic liver progression in the vast majority of patients, in turn reducing the risk of HCC. Even in HBeAg positive patients, treatment-induced HBeAg loss and seroconversion to antiHBe characterizes the induction of a partial immune control often leading to a low replicative phase of the chronic HBV infection and good outcomes.
Treatment in chronic HBV infection is indicated in - presence of advanced fibrosis/cirrhosis (LSM >11 KPA) or patients with significant fibrosis (LSM >8 or APRI >1.5 or >F2 on liver biopsy) with high viral load (>2000 IU/ml) or significantly elevated ALT (x2 ULN). Presence of any of these factors is known to increase the risk of development of cirrhosis and hepatocellular carcinoma. TAF in non-cirrhotic patients (LSM <8 KPA) with normal ALT and low viral load (HBV DNA <2000 IU/ml) (currently treatment ineligible) as compared to delayed initiation (on demand) might reduce HCC risk, progression of liver fibrosis and reduction in HBsAg levels. As TAF is known to have favorable effects on the overall long-term outcome, the main clinical challenge is to identify the patients at risk of HCC and cirrhosis who warrant early antiviral therapy.
Read the detailed description
Aim and Objective - To study the safety and efficacy of TAF as compared to initiation based on current criteria in patients with non-cirrhotic chronic HBV infection and normal ALT and low viral load.
Methodology:
Study population: The study will be conducted on the treatment naïve consecutive patients having non-cirrhotic chronic HBV infection and normal ALT and low viral load seen at the outpatient clinics/wards of Department of Hepatology, ILBS, New Delhi.
Study design:
- A prospective, randomized, single center open label study.
Study period: 5 years from the last patient enrollment
Sample size with justification: All consecutive cases consenting to be a participant in this study and meeting inclusion and exclusion criteria will be enrolled. Considering the incidence of 20% for the composite end-point in patients without TAF and 5% for patients on TAF, with power of 80% and alpha error of 5%, 176 patients (88 patients in each arm) need to be enrolled. Considering the attrition rate of ~15%, we decide to enroll 100 patients in each arm.
Intervention
- TAF 25 mg OD vs no treatment x 5 years and beyond
- Tests - Baseline - USG abdomen, ALT, Creatinine, DEXA, HBVDNA, HBeAg, HBsAg (quant), Fibroscan
- 6 monthly - ALT
- 1 yearly - USG abdomen, ALT, Creatinine, DEXA, HBVDNA, HBeAg, HBsAg (quant), Fibroscan
- No liver biopsy
Statistical Analysis:
Data will be reported as mean + SD. Categorical variables will be compared using the chi-square test or Fisher exact test. Normal continuous variables will be compared using the Student's t test Non normal continuous variables will be compared using the Mann Whitney rank-sum test (unpaired data) or the Wilcoxon test (paired data). The actuarial probability of survival will be calculated by the Kaplan-Meier method and compared using the log-rank test. A Cox regression analysis will be performed to identify independent prognostic factors for survival. Univariate and multivariate analysis will be used whenever applicable.
Adverse effects:
Most common- headache, nausea, and fatigue; (1% to 10%): Abdominal pain, nausea, diarrhea, dyspepsia, elevated serum amylase, vomiting, flatulence, abdominal distension; Common (1% to 10%): Rash, pruritus, elevated ALT; Uncommon (0.1% to 1%): Treatment ALT flares.
- Conditions
- Non-cirrhotic, Chronic Hepatitis B
- Being tested
- Tenofovir alafenamide fumarate
- 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 fumarateDrug
- TAF 25 mg OD vs no treatment x 5 years and beyond
| Study group | Role | What they receive |
|---|---|---|
| Tenofovir Alafenamide Fumarate | Experimental | • TAF 25 mg OD vs no treatment x 5 years and beyond Receives: Drug: Tenofovir alafenamide fumarate |
| No Treatment Arm | No intervention | No treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients with HBV DNA <2000 IU/ml, normal ALT and no significant fibrosis (as per APASL 2015).
Any two of the following -
- Significant fibrosis (LSM >8 Kpa or APRI >1.5)
- Persistently elevated ALT (2 consecutive ALT >30 U/ml 3-6m apart)
- HBV DNA >2000 IU/ml
Measured: upto 5 Years
Secondary outcomes (16)
Incidence of HCC
Measured: upto 3 years
Incidence of HCC
Measured: upto 5 years
Percentage of patients with LSM >8 Kpa
Measured: upto 5 Years
Percentage of patients with LSM >11 Kpa
Measured: upto 5 Years
Number of subjects with no progression of fibrosis
Measured: upto 5 Years
Percentage of patients with APRI score >1.5 and >2
Measured: upto 5 Years
Percentage of patients with HBV DNA >2000 IU/ml
Measured: upto 5 Years
Percentage of patients with undetectable HBV DNA
Measured: upto 5 Years
Percentage of patients with HBsAg loss and HBsAg seroconversion
Measured: upto 5 Years
Log HBsAg reduction
Measured: upto 5 Years
Percentage of patients with HBeAg loss and HBeAg seroconversion in HBeAg+ chronic hepatitis B
Measured: upto 5 Years
Percentage of patients with ALT > ULN, >2 times and 5 times ULN
Measured: upto 5 Years
Treatment related adverse effects of TAF
Measured: upto 5 Years
Non-compliant to treatment or monitoring
Measured: upto 5 years
Death
Measured: upto 5 years
Treatment related severe adverse effects
Measured: upto 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2022
- Study start23 Feb 2022
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-cirrhotic, Chronic Hepatitis BStudies of the same condition, open and under way.
- More trials run by Institute of Liver and Biliary Sciences, IndiaThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute of Liver and Biliary Sciences, India
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05195450
- Sponsor's protocol ID
- ILBS-HBV-02
- Status last verified
- Feb 2022
- First submitted
- 4 Jan 2022
- Last updated
- 28 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TAF (Tenofovir Alafenamide) for Preventing Progression of Liver Disease in Non-cirrhotic Chronic HBV Infection With Normal ALT and Low Viral Load - a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05195450
- Acronym / sponsor ID
- ILBS-HBV-02
- Conditions
- Non-cirrhotic, Chronic Hepatitis B
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Institute of Liver and Biliary Sciences, IndiaUniversity, hospital or other
- Study start
- 23 Feb 2022 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 19 Jan 2022 (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 main goal of therapy for patients with chronic HBV infection with no significant liver disease is to improve survival and quality of life by preventing disease progression, development of liver cirrhosis and consequently HCC development. The likelihood of achieving these goals depends on the timing of therapy during the natural course of the infection but also on the stage of the disease and the patients' age when treatment is started. The inhibition of viral replication and normalization of ALT by antiviral treatment has been shown to achieve the elimination of chronic HBV-induced necroinflammatory activity and progressive fibrotic liver progression in the vast majority of patients, in turn reducing the risk of HCC. Even in HBeAg positive patients, treatment-induced HBeAg loss and seroconversion to antiHBe characterizes the induction of a partial immune control often leading to a low replicative phase of the chronic HBV infection and good outcomes.
Treatment in chronic HBV infection is indicated in - presence of advanced fibrosis/cirrhosis (LSM >11 KPA) or patients with significant fibrosis (LSM >8 or APRI >1.5 or >F2 on liver biopsy) with high viral load (>2000 IU/ml) or significantly elevated ALT (x2 ULN). Presence of any of these factors is known to increase the risk of development of cirrhosis and hepatocellular carcinoma. TAF in non-cirrhotic patients (LSM <8 KPA) with normal ALT and low viral load (HBV DNA <2000 IU/ml) (currently treatment ineligible) as compared to delayed initiation (on demand) might reduce HCC risk, progression of liver fibrosis and reduction in HBsAg levels. As TAF is known to have favorable effects on the overall long-term outcome, the main clinical challenge is to identify the patients at risk of HCC and cirrhosis who warrant early antiviral therapy.
Detailed description
Aim and Objective - To study the safety and efficacy of TAF as compared to initiation based on current criteria in patients with non-cirrhotic chronic HBV infection and normal ALT and low viral load.
Methodology:
Study population: The study will be conducted on the treatment naïve consecutive patients having non-cirrhotic chronic HBV infection and normal ALT and low viral load seen at the outpatient clinics/wards of Department of Hepatology, ILBS, New Delhi.
Study design:
- A prospective, randomized, single center open label study.
Study period: 5 years from the last patient enrollment
Sample size with justification: All consecutive cases consenting to be a participant in this study and meeting inclusion and exclusion criteria will be enrolled. Considering the incidence of 20% for the composite end-point in patients without TAF and 5% for patients on TAF, with power of 80% and alpha error of 5%, 176 patients (88 patients in each arm) need to be enrolled. Considering the attrition rate of ~15%, we decide to enroll 100 patients in each arm.
Intervention
- TAF 25 mg OD vs no treatment x 5 years and beyond
- Tests - Baseline - USG abdomen, ALT, Creatinine, DEXA, HBVDNA, HBeAg, HBsAg (quant), Fibroscan
- 6 monthly - ALT
- 1 yearly - USG abdomen, ALT, Creatinine, DEXA, HBVDNA, HBeAg, HBsAg (quant), Fibroscan
- No liver biopsy
Statistical Analysis:
Data will be reported as mean + SD. Categorical variables will be compared using the chi-square test or Fisher exact test. Normal continuous variables will be compared using the Student's t test Non normal continuous variables will be compared using the Mann Whitney rank-sum test (unpaired data) or the Wilcoxon test (paired data). The actuarial probability of survival will be calculated by the Kaplan-Meier method and compared using the log-rank test. A Cox regression analysis will be performed to identify independent prognostic factors for survival. Univariate and multivariate analysis will be used whenever applicable.
Adverse effects:
Most common- headache, nausea, and fatigue; (1% to 10%): Abdominal pain, nausea, diarrhea, dyspepsia, elevated serum amylase, vomiting, flatulence, abdominal distension; Common (1% to 10%): Rash, pruritus, elevated ALT; Uncommon (0.1% to 1%): Treatment ALT flares.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tenofovir Alafenamide Fumarate | Experimental | Drug: Tenofovir alafenamide fumarate• TAF 25 mg OD vs no treatment x 5 years and beyond |
| No Treatment Arm | No intervention | –No treatment |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- HBsAg+
- Persistent normal ALT 3-6m apart (<30 IU/ml in male and <20 IU/ml in female)
- HBV DNA < 2000 IU/ml
- LSM <8 Kpa
Key exclusion criteria (9 listed)
- Prior NUC/IFN exposure
- Renal dysfunction (Serum Creatinine >1.5 mg/dl)
- Known liver cirrhosis/ esophageal varices
- Any clinical decompensation (CD)
- Pre-existing hepatocellular carcinoma
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 fumarate• TAF 25 mg OD vs no treatment x 5 years and beyond | Drug | Tenofovir Alafenamide Fumarate |
Primary outcome
Percentage of patients with HBV DNA <2000 IU/ml, normal ALT and no significant fibrosis (as per APASL 2015).
Time frame: upto 5 Years
Any two of the following - 1. Significant fibrosis (LSM >8 Kpa or APRI >1.5) 2. Persistently elevated ALT (2 consecutive ALT >30 U/ml 3-6m apart) 3. HBV DNA >2000 IU/ml
16 secondary outcomes
Incidence of HCC
Time frame: upto 3 years
Incidence of HCC
Time frame: upto 5 years
Percentage of patients with LSM >8 Kpa
Time frame: upto 5 Years
Percentage of patients with LSM >11 Kpa
Time frame: upto 5 Years
Number of subjects with no progression of fibrosis
Time frame: upto 5 Years
Percentage of patients with APRI score >1.5 and >2
Time frame: upto 5 Years
Percentage of patients with HBV DNA >2000 IU/ml
Time frame: upto 5 Years
Percentage of patients with undetectable HBV DNA
Time frame: upto 5 Years
Percentage of patients with HBsAg loss and HBsAg seroconversion
Time frame: upto 5 Years
Log HBsAg reduction
Time frame: upto 5 Years
Percentage of patients with HBeAg loss and HBeAg seroconversion in HBeAg+ chronic hepatitis B
Time frame: upto 5 Years
Percentage of patients with ALT > ULN, >2 times and 5 times ULN
Time frame: upto 5 Years
Treatment related adverse effects of TAF
Time frame: upto 5 Years
Non-compliant to treatment or monitoring
Time frame: upto 5 years
Death
Time frame: upto 5 years
Treatment related severe adverse effects
Time frame: upto 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2022.
- Individual participant dataSharing planned: No
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tenofovir alafenamide fumarate in people with Non-cirrhotic, Chronic Hepatitis B, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
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 4 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: looking for participants now, as of the sponsor's last update on 28 Feb 2022. 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 India. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr Ankur Jindal, DM (01146300000, ankur.jindal3@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients with HBV DNA <2000 IU/ml, normal ALT and no significant fibrosis (as per APASL 2015). (time frame: upto 5 Years). 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 28 Feb 2022.