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

University Health Network, Toronto

Status and phase

Unknown

Phase 4

Conditions

Hepatitis B, Chronic

Treatments

Drug: Tenofovir Alafenamide

Study type

Interventional

Funder types

Other

Identifiers

NCT04070079

CO-US-320-4667

Details and patient eligibility

About

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).

Full 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.

Enrollment

15 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No 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