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.
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
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
Single group
VIR-2218 and peginterferon alfa-2a
Drug(VIR-2218) administered as a lead-in followed by combination with peginterferon alfa-2a
Decline in log quantitative HBsAg level
To evaluate the effect of administration of VIR-2218 in combination with peginterferon alfa-2a on qHBsAg levels
Changes in innate and adaptive host immune responses to HBV during and after treatment.
To evaluate the effects of VIR-2218 in combination with peginterferon alfa-2a on peripheral and intrahepatic immune responses in non-cirrhotic adults with chronic HBV infection
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)
Partial cure. An alternative goal of treatment of chronic hepatitis B
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
The goal of treatment of chronic hepatitis B
Safety
To evaluate the safety and tolerability of VIR-2218 in combination with peginterferon alfa-2a in non-cirrhotic adults with chronic HBV infection
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