Testing VIR-2218 and Peginterferon Alfa-2a for Chronic Hepatitis B

A Pilot Study of the Combination of VIR-2218 and Peginterferon Alfa-2a for Chronic Hepatitis B

This study is testing if a combination of two drugs, VIR-2218 and peginterferon alfa-2a, can help adults with mild chronic hepatitis B feel better and possibly achieve a functional cure.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: prednisone
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT06092333 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of two drugs, VIR-2218 and peginterferon alfa-2a, in treating adults with mild or inactive chronic hepatitis B virus (HBV) infection. Participants aged 18 to 65 will undergo screening, including blood tests and liver imaging, before receiving monthly injections of VIR-2218 for six months, followed by weekly injections of peginterferon for an additional twelve weeks. The primary goal is to measure the decline in hepatitis B surface antigen levels, while secondary objectives include assessing safety and the potential for a functional cure. The study will last over two years, with follow-up assessments to monitor treatment response and durability.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with mild or inactive chronic hepatitis B infection and specific viral load criteria.

Not a fit: Patients with active hepatitis B infection, cirrhosis, or those who are pregnant or lactating may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to a functional cure for chronic hepatitis B, significantly improving patient outcomes.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific combination is being tested for the first time.

Eligibility criteria

* INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Age \>=18-65 years
2. HBsAg positive with a level \<2,000 IU/mL at the time of screening
3. Hepatitis B e antigen negative
4. HBV DNA levels \<10,000 IU/mL on two occasions at least 24 weeks apart with the second being at time of screening
5. ALT level \<=2 ULN (using sex-specific cut-offs of normal 35 U/L for males and 25 U/L for females) based on at least two determinations taken at least 24 weeks apart with the second being at time of screening

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Pregnancy or lactation
2. For women of childbearing potential, inability, or unwillingness to use highly effective contraception during study drug dosing and for an additional 24 weeks after the end of study drug administration.
3. For males of reproductive potential: Unable or unwilling to use condoms consistently in addition to female partner using another adequate contraceptive method to ensure effective contraception with partner during study participation and for an additional 24 weeks after the end of study medication administration. Patients who have underwent surgical sterilization (vasectomy) will still require female partner to utilize an additional adequate contraception method.
4. Known history of hypersensitivity or contraindication to an siRNA, oligonucleotide, or GalNAc or any interferon product
5. Current use of oral theophylline and methadone
6. Any treatment for HBV within the last 24 weeks
7. Prior exposure to a siRNA
8. Co-infection with HDV as defined by the presence of anti-HDV in serum.
9. Co-infection with HCV as defined by the presence of anti-HCV and HCV RNA in serum.
10. Co-infection with HIV as defined by the presence of anti-HIV in serum
11. Cirrhosis either diagnosed by a prior liver biopsy at any time or, if not available, by a transient elastography score \>13 kPa
12. Decompensated liver disease as defined by serum bilirubin \>2.5 mg/dL (with direct bilirubin \> 1.5 mg/dL), prothrombin time of greater than 2 seconds prolonged, a serum albumin of less than 3.5 g/dL, or a history of ascites, variceal bleeding or hepatic encephalopathy
13. Hepatocellular carcinoma (HCC), or the presence of a mass on imaging studies of the liver that is suggestive of HCC, or an alpha-fetoprotein level of greater than 500 ng/mL
14. Presence of other causes of liver disease, (i.e. hemochromatosis, Wilson disease, alcoholic liver disease, severe steatosis, alpha-1-anti-trypsin deficiency)
15. A history of solid organ or bone marrow transplant
16. Any current medical condition requiring the chronic use of more than 10 mg of prednisone (or its equivalent) daily or biologics (e.g. monoclonal antibody, interferon) within 3 months of screening.
17. Significant systemic illness other than liver diseases including congestive heart failure, renal failure, chronic pancreatitis and diabetes mellitus with poor control (hemoglobin A 1C (HgbA1C \>8.5)), that in the opinion of the investigator may interfere with therapy.
18. eGFR \< 60 ml/min, serum creatinine \> 1.3 mg/dl
19. Platelet count \<90 mm3/dL
20. Hgb \<12 g/dL for males and \<11 g/dL for females
21. White Blood cell count \< 2500 cells/mm3
22. Neutrophil count \< 1500 cell/mm3 (or \< 1000 cell/mm3 if considered a physiological variant in a subject of African descent)
23. Active ethanol/drug abuse/psychiatric problems such as major depression, schizophrenia, bipolar illness, obsessive-compulsive disorder, severe anxiety, or personality disorder that, in the investigator s opinion, might interfere with participation in the study.
24. History of malignancy or treatment for a malignancy within the past 3 years (except adequately treated carcinoma in situ or basal cell carcinoma of the skin).
25. History of immune-mediated disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune hepatitis, sarcoidosis, psoriasis of greater than mild severity, autoimmune uveitis), or cerebrovascular, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, (TSH \>10 or \<0.4mU/L) or uncontrolled seizure disorder, as determined by a study physician.
26. Use of another investigational agent within 90 days of screening
27. Use of any prohibited immunosuppressants (except short term use of prednisone as a steroid burst \[\<= 1 week of use\]) or cytotoxic medications
28. Presence of conditions that, in the opinion of the investigators, would not allow the patient to be followed in the current study.
29. Inability of subject to understand and the unwillingness to sign a written informed consent document

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Marc G Ghany, M.D. — National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Study coordinator: Elenita M Rivera, R.N.

Conditions Chronic Hepatitis B; Treatment; Functional Cure; Immune Response