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

NCT04070079 | Unknown Phase 4 DMC

• 1 other identifier: CO-US-320-4667
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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).

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (3)

• 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

• 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 1. HBsAg/HBeAg seroclearance 2. HBsAg/HBeAg seroconversion, 3. Serum quantitative HBsAg/HBeAg levels, 4. Serum HBV DNA levels 5. HBV RNA levels 6. Hepatitis B core-related Antigen (HBcrAg) levels; 7. ALT levels.

  3 years

• 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

Study Arms (1)

Tenofovir Alafenamide

OTHER

Tenofovir Alafenamide 25mg, Dosed orally, once daily with or without food.

Drug: Tenofovir Alafenamide

Interventions

Tenofovir Alafenamide DRUG

TAF 25mg once daily orally, for 48 weeks

Tenofovir Alafenamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Toronto General Hospital

Toronto, Ontario, M3G 2C4, Canada

RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

tenofovir alafenamide

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Hepatology | Director Toronto Centre for Liver Disease | Director Viral Hepatitis Care Network (VIRCAN) | Professor of Medicine, University of Toronto |

Study Record Dates

• First Submitted: March 29, 2019
• First Posted: August 28, 2019
• Study Start: January 29, 2019
• Primary Completion: August 30, 2022
• Study Completion: December 31, 2022
• Last Updated: August 28, 2019

Record last verified: 2019-08

Locations

CA (1)