- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04070079
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
-
-
Ontario
-
Toronto, Ontario, Canada, M3G 2C4
- Recruiting
- Toronto General Hospital
-
Contact:
- Pujitha Rao
- Phone Number: 6651 4163404800
- Email: pujitha.rao@uhn.ca
-
-
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.
|
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
|
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.
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
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis, Chronic
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Tenofovir
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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