Testing a new drug for chronic hepatitis B infection

Phase II Investigator-Initiated Study to Understand the Vaccinal Effect of HBsAg Monoclonal Ab VIR-3434 in Chronic Hepatitis B Infection

This study is testing a new drug called VIR-3434 to see if it can help people with chronic hepatitis B infection improve their condition over a year of treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: University Health Network, Toronto (other)
• Drugs / interventions: prednisone
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT06216470 on ClinicalTrials.gov

What this trial studies

This Phase II interventional study aims to evaluate the vaccinal effect of VIR-3434, a monoclonal antibody targeting HBsAg, in patients with chronic hepatitis B infection. Participants will receive subcutaneous injections of VIR-3434 every four weeks for 48 weeks, followed by a 48-week follow-up period. The study will enroll 15 patients who have been on stable nucleos(t)ide therapy and will undergo fine-needle aspiration procedures at specified intervals to assess the drug's effectiveness. The study is open-label, meaning all participants will receive the treatment without a placebo group.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with chronic hepatitis B infection who have been on stable nucleos(t)ide therapy for over a year.

Not a fit: Patients with acute hepatitis B infection or those not on stable nucleos(t)ide therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could lead to a significant reduction or clearance of hepatitis B virus in affected patients.

How similar studies have performed: While this approach is novel, previous studies targeting HBsAg have shown promise, indicating potential for success.

Eligibility criteria

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

Where this trial is running

Toronto, Ontario

• University Health Network — Toronto, Ontario, Canada (RECRUITING)

Study contacts

• Principal investigator: Jordan Feld, MD — University Health Network, Toronto
• Study coordinator: Jordan Feld, MD

Conditions: Hepatitis B, Chronic