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

NCT06092333 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10001606001606-DK
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Chronic hepatitis B virus (HBV) infection affects 292 million people worldwide; 887,000 die each year from cirrhosis, liver cancer, and related issues. Treatment options are limited. Objective: To test 2 drugs (VIR-2218 and peginterferon) in people with mild or inactive HBV infection. Eligibility: People aged 18 to 65 years with mild or inactive HBV infection. Design: Participants will be screened. They will have blood tests and an eye exam. They will have imaging scans of the liver to check the health of the liver. Participants will be in the study for over 2 years. VIR-2218 is an injection given under the skin of the stomach, upper arm, or thigh. Participants will come to the clinic to receive this injection once a month for 6 months. Peginterferon is also injected under the skin. Participants will have this shot once a week for 6 months. They may either inject themselves at home or come to the clinic to get the injections. Participants will get just the VIR-2218 for 3 months, then both shots for 3 months, then just the peginterferon for 3 months. Participants will have two 3-day stays in the hospital. Tests will include: Liver biopsy. A sample of tissue will be taken from their liver. After the procedure, participants will lie on their right side for 2 hours and then on their back for 4 hours. Fine needle aspiration. A small needle will be used to collect cells from the liver. After the last injection of peginterferon, follow-up visits will continue in the outpatient clinic every 4 to 12 weeks.

Conditions

Chronic Hepatitis B

Keywords

Chronic Hepatitis B; Treatment; Functional Cure; Immune Response

Outcome Measures

Primary Outcomes (1)

• Decline in log quantitative HBsAg level

  To evaluate the effect of administration of VIR-2218 in combination with peginterferon alfa-2a on qHBsAg levels

  6 months after discontinuation of all treatment

Secondary Outcomes (4)

• Changes in innate and adaptive host immune responses to HBV during and after treatment.

  Within the first 6 hours after peginterferon injection; Baseline to week 12, from Baseline to week 36 and from Baseline to week 84

• HBV DNA <10 IU/ml at end of treatment and 6 months off treatment. The response will be reported as HBV DNA <LLOQ target detected (TD) or target not detected (TND)

  6 months off-treatment

• Functional cure which is defined as undetectable HBsAg (<0.085 IU/ml) AND sustained suppression of HBV DNA [< LLOQ], <10 IU/ml)] for more than 6 months after discontinuation of all treatment

  > 6 months after discontinuation of all treatment

• Safety

  End of treatment 6 months off-treatment

Study Arms (1)

Single arm, open label

OTHER

open label

Drug: VIR-2218 and peginterferon alfa-2a

Interventions

VIR-2218 and peginterferon alfa-2a DRUG

(VIR-2218) administered as a lead-in followed by combination with peginterferon alfa-2a

Single arm, open label

Eligibility Criteria

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

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Age \>=18-65 years
• HBsAg positive with a level \<2,000 IU/mL at the time of screening
• Hepatitis B e antigen negative
• HBV DNA levels \<10,000 IU/mL on two occasions at least 24 weeks apart with the second being at time of screening
• 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

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Pregnancy or lactation
• 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.
• 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.
• Known history of hypersensitivity or contraindication to an siRNA, oligonucleotide, or GalNAc or any interferon product
• Current use of oral theophylline and methadone
• Any treatment for HBV within the last 24 weeks
• Prior exposure to a siRNA
• Co-infection with HDV as defined by the presence of anti-HDV in serum.
• Co-infection with HCV as defined by the presence of anti-HCV and HCV RNA in serum.
• Co-infection with HIV as defined by the presence of anti-HIV in serum
• Cirrhosis either diagnosed by a prior liver biopsy at any time or, if not available, by a transient elastography score \>13 kPa
• 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
• 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
• Presence of other causes of liver disease, (i.e. hemochromatosis, Wilson disease, alcoholic liver disease, severe steatosis, alpha-1-anti-trypsin deficiency)

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

peginterferon alfa-2a

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 Officials

• Marc G Ghany, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elenita M Rivera, R.N.

CONTACT

(301) 435-6125; erivera@cc.nih.gov

Marc G Ghany, M.D.

CONTACT

(301) 402-5115; mg228m@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2023
• First Posted: October 23, 2023
• Study Start: January 31, 2025
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: March 18, 2026

Record last verified: 2026-03-13

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)