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

Primary Purpose

Hepatitis B, Chronic

Status
Unknown status
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Tenofovir Alafenamide
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Toronto General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Tenofovir Alafenamide

Arm Description

Tenofovir Alafenamide 25mg, Dosed orally, once daily with or without food.

Outcomes

Primary Outcome Measures

TAF-mediated reduction of inflammatory gene expression in intraheaptic immune cells
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.
TAF-mediated reduction of serological markers of HBV replication
Existing and experimental biomarkers of HBV replication will be measured to compare the viral response to the immune response HBsAg/HBeAg seroclearance HBsAg/HBeAg seroconversion, Serum quantitative HBsAg/HBeAg levels, Serum HBV DNA levels HBV RNA levels Hepatitis B core-related Antigen (HBcrAg) levels; ALT levels.
TAF-mediated reduction of intrahepatic HBV replication intermediates and cccDNA levels
HBV replication intermediates and cccDNA measured as copies/mg of liver tissue

Secondary Outcome Measures

Full Information

First Posted
March 29, 2019
Last Updated
August 23, 2019
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT04070079
Brief Title
Tenofovir Alafenamide With Fine Needle Aspiration Biopsy in Chronic Hepatitis B:
Official Title
Evaluation of Intrahepatic Immune and Virological Response to Tenofovir Alafenamide With Fine Needle Aspiration Biopsy in Chronic Hepatitis B: an Investigator-Initiated, Cohort Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Unknown status
Study Start Date
January 29, 2019 (Actual)
Primary Completion Date
August 30, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tenofovir Alafenamide
Arm Type
Other
Arm Description
Tenofovir Alafenamide 25mg, Dosed orally, once daily with or without food.
Intervention Type
Drug
Intervention Name(s)
Tenofovir Alafenamide
Intervention Description
TAF 25mg once daily orally, for 48 weeks
Primary Outcome Measure Information:
Title
TAF-mediated reduction of inflammatory gene expression in intraheaptic immune cells
Description
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.
Time Frame
3 years
Title
TAF-mediated reduction of serological markers of HBV replication
Description
Existing and experimental biomarkers of HBV replication will be measured to compare the viral response to the immune response HBsAg/HBeAg seroclearance HBsAg/HBeAg seroconversion, Serum quantitative HBsAg/HBeAg levels, Serum HBV DNA levels HBV RNA levels Hepatitis B core-related Antigen (HBcrAg) levels; ALT levels.
Time Frame
3 years
Title
TAF-mediated reduction of intrahepatic HBV replication intermediates and cccDNA levels
Description
HBV replication intermediates and cccDNA measured as copies/mg of liver tissue
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M3G 2C4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pujitha Rao
Phone
4163404800
Ext
6651
Email
pujitha.rao@uhn.ca

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
It is undecided yet.

Learn more about this trial

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

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