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

Recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

15

Phase

  • 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

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
Intervention / Treatment
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

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

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)

January 29, 2019

Primary Completion (Anticipated)

August 30, 2022

Study Completion (Anticipated)

December 31, 2022

Study Registration Dates

First Submitted

March 29, 2019

First Submitted That Met QC Criteria

August 23, 2019

First Posted (Actual)

August 28, 2019

Study Record Updates

Last Update Posted (Actual)

August 28, 2019

Last Update Submitted That Met QC Criteria

August 23, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID 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.

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