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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04070079
Recruitment Status : Recruiting
First Posted : August 28, 2019
Last Update Posted : August 28, 2019
Information provided by (Responsible Party):
Harry Janssen, University Health Network, Toronto

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).

Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Drug: Tenofovir Alafenamide Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 29, 2019
Estimated Primary Completion Date : August 30, 2022
Estimated Study Completion Date : December 31, 2022

Arm Intervention/treatment
Tenofovir Alafenamide
Tenofovir Alafenamide 25mg, Dosed orally, once daily with or without food.
Drug: Tenofovir Alafenamide
TAF 25mg once daily orally, for 48 weeks

Primary Outcome Measures :
  1. 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.

  2. 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. 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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04070079

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Canada, Ontario
Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M3G 2C4
Contact: Pujitha Rao    4163404800 ext 6651   
Sponsors and Collaborators
University Health Network, Toronto
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Responsible Party: Harry Janssen, Chief of Hepatology | Director Toronto Centre for Liver Disease | Director Viral Hepatitis Care Network (VIRCAN) | Professor of Medicine, University of Toronto |, University Health Network, Toronto Identifier: NCT04070079    
Other Study ID Numbers: CO-US-320-4667
First Posted: August 28, 2019    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: It is undecided yet.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents