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

Hepatitis B, Chronic Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04070079
• Other study ID #: CO-US-320-4667
• Status: Recruiting
• Phase: Phase 4
• Start date: January 29, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: August 2019
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 31, 2022
• Est. primary completion date: August 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• Tenofovir Alafenamide
TAF 25mg once daily orally, for 48 weeks

Locations

Country	Name	City	State
Canada	Toronto General Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3 years
Primary	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.	3 years
Primary	TAF-mediated reduction of intrahepatic HBV replication intermediates and cccDNA levels	HBV replication intermediates and cccDNA measured as copies/mg of liver tissue	3 years