Tenofovir Alafenamide With Fine Needle Aspiration Biopsy in Chronic Hepatitis B:

August 23, 2019 updated by: Harry Janssen, University Health Network, Toronto

Evaluation of Intrahepatic Immune and Virological Response to Tenofovir Alafenamide With Fine Needle Aspiration Biopsy in Chronic Hepatitis B: an Investigator-Initiated, Cohort Study

The objective of this study is to identify immunological mechanisms that contribute to normalization of liver inflammation in chronic hepatitis B (CHB) patients starting the antiviral nucleoside analogue, Tenofovir alafenamide (TAF).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Investigator-initiated, phase 4 study in which recruited patients will receive, TAF 25mg once daily, for 48 weeks (Figure 1 and Table 1). The total duration of the study to End of Follow-up (EOF) will be 48 weeks. After Week 48, participants will be offered 2 years of TAF therapy. Sample collection 0, 12, 24 w was chosen to analyze immune responses based on ALT normalization rates. This mono-center study will be conducted at Toronto Centre for Liver Disease, Canada.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M3G 2C4
        • Recruiting
        • Toronto General Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • • Age >18 years

    • Chronic hepatitis B (HBsAg positive ≥ six months)
    • HBeAg positive or negative
    • ALT >19 for females and >30 for males (AASLD criteria)
    • HBV DNA>4 log IU/mL for HBeAg positive and >3 log for HBeAg negative patients
    • No oral antiviral treatment or IFN for ≥6 months
    • Adequate contraception. For males, at least one method of contraception should be used and for females, a barrier contraception method should be used in combination with one other form of contraception.
    • Written informed consent

Exclusion Criteria:

  • • Treatment with any investigational drug within 60 days of entry into this protocol

    • Immune-suppressive treatment within the previous 6 months
    • History of decompensated cirrhosis (defined as direct (conjugated)
    • bilirubin > 1.2 × ULN,
    • prothrombin time (PT) > 1.2 × ULN
    • platelets < 100,000/mm3
    • serum albumin < 3.5 g/dL
    • prior history of clinical hepatic decompensation (jaundice in the presence of cirrhosis, ascites, gastric bleeding, oesophageal varices or encephalopathy)
    • Liver transplantation
    • Co-infection with hepatitis C virus, hepatitis D virus or HIV
    • Other significant liver disease: alcoholic liver disease, drug-related liver disease, auto-immune hepatitis, hemochromatosis, Wilson's disease or alpha-1 antitrypsin deficiency
    • Estimated glomerular filtration rate <50 mL/min/1.73m2 or any significant renal disease.
    • Alpha-fetoprotein > 50 ng/ml
    • Pregnancy, breast-feeding
    • Other significant medical illness that might interfere with this study: significant pulmonary dysfunction in previous 6 months, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g. HIV positivity, auto-immune diseases, organ transplants other than cornea and hair transplant)
    • Substance abuse, such as alcohol (≥80 g/day), I.V. drugs and inhaled drugs in past 2 years. Current methadone usage is allowed.
    • Any other condition which in the opinion of the investigator would make the patient unsuitable for enrolment, or could interfere with the patient participating in and completing the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Tenofovir Alafenamide
Tenofovir Alafenamide 25mg, Dosed orally, once daily with or without food.
Drug: Tenofovir Alafenamide
TAF 25mg once daily orally, for 48 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
TAF-mediated reduction of inflammatory gene expression in intraheaptic immune cells
Time Frame: 3 years
Longitudinal samples collected from each patient will be used to measure changes in intrahepatic and peripheral innate and adaptive immune composition, function and gene expression from baseline to ALT normalization after starting TAF.
3 years
TAF-mediated reduction of serological markers of HBV replication
Time Frame: 3 years

Existing and experimental biomarkers of HBV replication will be measured to compare the viral response to the immune response

  1. HBsAg/HBeAg seroclearance
  2. HBsAg/HBeAg seroconversion,
  3. Serum quantitative HBsAg/HBeAg levels,
  4. Serum HBV DNA levels
  5. HBV RNA levels
  6. Hepatitis B core-related Antigen (HBcrAg) levels;
  7. ALT levels.
3 years
TAF-mediated reduction of intrahepatic HBV replication intermediates and cccDNA levels
Time Frame: 3 years
HBV replication intermediates and cccDNA measured as copies/mg of liver tissue
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Health Network, Toronto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 29, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 30, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 29, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 23, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 28, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 28, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 23, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CO-US-320-4667

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

It is undecided yet.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hepatitis B, Chronic

Clinical Trials on Tenofovir Alafenamide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings