Clinical trial NCT04070079: 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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hepatitis B, Chronic
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2019-08-28
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: TAF-mediated reduction of inflammatory gene expression in intraheaptic immune cells
timeFrame: 3 years
measure: TAF-mediated reduction of serological markers of HBV replication
timeFrame: 3 years
measure: TAF-mediated reduction of intrahepatic HBV replication intermediates and cccDNA levels
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
References: