Hepatitis B, Chronic
Conditions
Brief summary
This is a Phase II Investigator-Initiated Study to understand the vaccinal effect of HBsAg monoclonal Ab VIR-3434 in chronic hepatitis B infection. The purpose of this study is to test VIR-3434, an experimental drug that specifically targets the HBsAg of hepatitis B virus, to clear it from the body. This is an open label study and there is no placebo used in this study. All participants will receive the VIR-3434 for 48 weeks and then follow up in the study for 48 weeks. A total duration of approximately 104 weeks including screening period for the entire study.
Detailed description
The objective of this study is to evaluate the vaccinal effect of VIR-3434 in chronic HBeAg-negative hepatitis B (CHB) patients suppressed on nucleos(t)ide analogue therapy. Total 15 patients will be enrolled at single site. The participants will receive VIR-3434 300 mg subcutaneous injection every 4 weeks x 48 weeks and then follow up for 48 weeks. Total three Fine-needle aspiration (FNA) procedure will be performed during the study: before treatment, 3 days after the first injection and 3 days after the week24 injection.
Interventions
DRUGVIR-3434
VIR-3434 is a human monoclonal antibody that binds the antigenic loop present in all forms of the surface envelope protein (small, middle, and large HBsAg).
Sponsors
University Health Network, Toronto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 to ≤65 years 2. Chronic HBV infection with evidence of HBsAg-positivity x \> 6 months 3. Quantitative HBsAg 300 - 10,000 IU/mL 4. On stable nucleos(t)ide therapy \>1 year 5. HBV DNA \< 60 IU/mL on 2 occasions at least 12 weeks apart 6. ALT ≤ 45 U/L on 2 occasions at least 12 weeks apart 7. Female subjects must have a negative pregnancy test or confirmation of postmenopausal status. Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and on Day 1, cannot be breast feeding, and must be willing to use highly effective methods of contraception 14 days before study drug administration through the study participation. Female subjects must also agree to refrain from egg donation and in vitro fertilization from the time of study drug administration through the study participation. 8. Male subjects with female partners of child-bearing potential must agree to meet 1 of the following contraception requirements from the time of study drug administration through the study participation: documentation of vasectomy or azoospermia, or male condom use plus partner use of 1 of the contraceptive options listed for contraception for WOCBP. Male subjects must also agree to not donate sperm from the time of study drug administration through the study participation. 9. Able and willing to sign informed consent
Exclusion criteria
1. History of cirrhosis as evidenced by prior Liver Elastography (Fibroscan) \> 12 kilopascals (kPa), liver biopsy (F4 by METAVIR) or clinical evidence of decompensation (ascites, hepatic encephalopathy) 2. History of or current hepatocellular carcinoma 3. Hepatitis C Virus (HCV) RNA or anti-Hepatitis D Virus (HDV) positive 4. HIV co-infection 5. Pregnancy or lactation 6. Alanine Aminotransferase (ALT) \> 45 U/L 7. History of chronic liver disease other than HBV aside from fatty liver documented only on US 8. Use of peginterferon therapy for HBV infection within past 12 months 9. Use of chronic immunosuppressive medications at a dose equivalent to 10 mg daily of prednisone or greater within past 6 months 10. Other significant medical illness that might interfere with this study: significant pulmonary dysfunction in previous 6 months, malignancy other than non-melanoma skin cancer in previous 5 years, immunodeficiency syndrome 11. Subject has received any investigational drug (including any investigational vaccines) within 90 days or 5 half-lives (whatever is longer) before screening for this study or is currently enrolled in an investigational study 12. Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments, such as liver FNAs 13. Platelet count \< 120,000,000,000/L 14. The International Normalised Ratio (INR) \> 1.3 15. Bilirubin \> 40 µmol/L 16. Hemoglobin \< 110 g/dL for women or 120 g/dL for men 17. estimated Glomerular Filtration Rate (eGFR) \< 45 cc/min 18. Alpha Fetoprotein (AFP) \> 50 ng/mL 19. Prior liver or other solid organ transplantation 20. Patients on anticoagulation therapy or with any bleeding diathesis 21. Patients with hemoglobinopathy (thalassemia, sickle cell disease etc) 22. Other significant liver disease: alcoholic liver disease, autoimmune hepatitis, hemochromatosis, primary biliary cholangitis, primary sclerosing cholangitis, Wilson Disease or alpha-1 antitrypsin deficiency - as documented in clinical history 23. Unable to provide informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in log Quantitative HBsAg | from baseline through study completion, an average of 2 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute and change of HBV core-related Ag | from baseline through study completion, an average of 2 year | — |
| Proportion of subjects with HBsAg loss | from baseline through study completion, an average of 2 year | — |
| Absolute and change of Hepatitis B Virus (HBV) RNA | from baseline through study completion, an average of 2 year | — |
| Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) with study treatment | from baseline through study completion, an average of 2 year | Frequency of AEs and SAEs with VIR-3434 administration in combination with NA therapy for CHB |
| Frequency of AEs and SAEs due to hepatic FNA | from baseline through study completion, an average of 2 year | — |
| HBeAg seroconversion | from baseline through study completion, an average of 2 year | Proportion of subject with HBeAg seroconversion |
Countries
Canada
Contacts
Primary ContactJordan Feld, MD
Backup ContactJiayun Chen
Outcome results
None listed