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

Chronic Hepatitis B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06092333
• Other study ID #: 10001606
• Secondary ID: 001606-DK
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 19, 2024
• Est. completion date: June 30, 2026

Study information

• Verified date: May 6, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Jaha F Norman-Wheeler
• Phone: (301) 435-6122
• Email: jaha.norman-wheeler[@]nih.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Study Description: Up to 50 untreated, adult, male and female subjects with hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) with low level viremia and antigenemia (hepatitis B surface antigen (HBsAg)) without cirrhosis will be screened in order to enroll 10 subjects in an open-label, phase 2a, single site (NIH Clinical Center), single arm, proof-of-concept study of a siRNA (VIR-2218) administered as a lead-in followed by combination with peginterferon alfa-2a. The primary endpoint of the study is log decline in quantitative HBsAg (qHBsAg) level. Secondary objectives include safety, functional cure defined as undetectable HBsAg (

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

• 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. Any treatment for HBV within the last 24 weeks.

6. Prior exposure to a siRNA

7. Co-infection with HDV as defined by the presence of anti-HDV in serum.

8. Co-infection with HCV as defined by the presence of anti-HCV and HCV RNA in serum.

9. Co-infection with HIV as defined by the presence of anti-HIV in serum

10. Cirrhosis either diagnosed by a prior liver biopsy at any time or, if not available, by a transient elastography score >13 kPa

11. 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

12. 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

13. Presence of other causes of liver disease, (i.e. hemochromatosis, Wilson disease, alcoholic liver disease, severe steatosis, alpha-1-anti-trypsin deficiency)

14. A history of solid organ or bone marrow transplant

15. 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.

16. 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.

17. eGFR < 60 ml/min, serum creatinine > 1.3 mg/dl

18. Platelet count <90 mm3/dL

19. Hgb <12 g/dL for males and <11 g/dL for females

20. White Blood cell count < 2500 cells/mm3

21. Neutrophil count < 1500 cell/mm3 (or < 1000 cell/mm3 if considered a physiological variant in a subject of African descent)

22. 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.

23. 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).

24. 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.

25. Use of another investigational agent within 90 days of screening

26. Use of any prohibited immunosuppressants (except short term use of prednisone as a steroid burst [<= 1 week of use]) or cytotoxic medications

27. Presence of conditions that, in the opinion of the investigators, would not allow the patient to be followed in the current study.

28. Inability of subject to understand and the unwillingness to sign a written informed consent document

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

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

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Decline in log quantitative HBsAg level	To evaluate the effect of administration of VIR-2218 incombination with peginterferon alfa-2a on qHBsAg levels	6 months after discontinuation of all treatment
Secondary	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	Within the first 6 hours after peginterferon injection; Baseline to week 12, from Baseline to week 36 and from Baseline to week 84
Secondary	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	6 months off-treatment
Secondary	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	> 6 months after discontinuation of all treatment
Secondary	Safety	To evaluate the safety and tolerability of VIR-2218 in combination with peginterferon alfa-2a in non-cirrhotic adults with chronic HBV infection	End of treatment 6 months off-treatment

External Links

•   NIH Clinical Center Detailed Web Page