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

Sponsor

University Health Network, Toronto (Other)

Overall Status

Recruiting

CT.gov ID

NCT04070079

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

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).

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.

Study Design

Study Type:

Interventional

Anticipated 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 :

Jan 29, 2019

Anticipated Primary Completion Date :

Aug 30, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

TAF-mediated reduction of inflammatory gene expression in intraheaptic immune cells [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.
TAF-mediated reduction of serological markers of HBV replication [3 years]
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 [3 years]
HBV replication intermediates and cccDNA measured as copies/mg of liver tissue

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Toronto General Hospital	Toronto	Ontario	Canada	M3G 2C4

Sponsors and Collaborators

University Health Network, Toronto

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

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

ClinicalTrials.gov Identifier:

NCT04070079

Other Study ID Numbers: