This study is NOT currently recruiting participants.
Number
001606-DK
Sponsoring Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Recruitment Detail
Type: Recruitment has not started Gender: Male & Female Min Age: 18 Years Max Age: 65 Years
Referral Letter Required
No
Population Exclusion(s)
Adults who are or may become unable to consent;Children;Fetuses;Neonates;Pregnant Women
Keywords
Chronic Hepatitis B; Treatment; Functional Cure; Immune Response
Recruitment Keyword(s)
None
Condition(s)
Chronic Hepatitis B
Investigational Drug(s)
VIR-2218 Peginterferon alfa-2a
Investigational Device(s)
Intervention(s)
Drug: VIR-2218 and peginterferon alfa-2a
Supporting Site
National Institute of Diabetes and Digestive and Kidney Diseases
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.
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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
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
Principal Investigator
Referral Contact
For more information: