This study is NOT currently recruiting participants.
Number
12-DK-0071
Sponsoring Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 18 Max Age: 40
Referral Letter Required
No
Population Exclusion(s)
Children
Keywords
Chronic Hepatitis B
Recruitment Keyword(s)
Hepatitis B
Condition(s)
Hepatitis B; Chronic Hepatitis B e Antigen Positive
Investigational Drug(s)
Entecavir, Peginterferon Peginterferon alfa-2a
Investigational Device(s)
None
Intervention(s)
Drug: Entecavir and Peginterferon
Supporting Site
National Institute of Diabetes and Digestive and Kidney Diseases
- Chronic hepatitis B generally has two phases. The first phase has a high virus count and active liver disease, and the second phase has a low virus count and inactive liver disease. However, people who have the hepatitis B virus at birth or get it as an infant often have a phase with a high virus count but no liver disease. This is called the immune-tolerant phase. These people may stay healthy for years, but in their 20s or 30s they will start to develop liver disease.
- Earlier attempts to treat the virus before it causes liver disease have not been successful. However, researchers want to test a new combination of drugs for this condition. Entecavir is designed to reduce the levels of the hepatitis B virus in the blood. Peginterferon is designed to enhance the immune response against the virus These two drugs may prevent people with immune-tolerant hepatitis B from developing active liver disease later in life.
Objectives:
- To determine whether entecavir and peginterferon can be used to treat people in the immune-tolerant phase of chronic hepatitis B.
Eligibility:
- Individuals at least 18 years of age who have chronic hepatitis B and are in the immune-tolerant phase of infection.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
- Participants will be divided into two groups. One group will receive the study drugs. The other group will be monitored, but will have no treatment.
- Study drug participants will receive entecavir alone for the first 8 weeks. They will then have peginterferon weekly and entecavir daily for 40 weeks, for a total of 48 weeks.
- Both groups will be monitored with frequent blood tests and other studies.
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INCLUSION CRITERIA: 1. Enrolled in the Hepatitis B Research Network (HBRN) Cohort Study or completed the necessary components of the Cohort baseline evaluation by the end of the baseline visit for this study 2. greater than or equal to 18 years of age at the baseline visit (day 0). Patients >50 years of age at the baseline visit need to have a liver biopsy as standard of care with HAI less than or equal to 3 and Ishak fibrosis score less than or equal to 1 within 96 weeks prior to the baseline visit. 3. Documented chronic HBV infection as evidenced by detection of HBsAg in serum for greater than or equal to 24 weeks prior to the baseline visit OR at least one positive HBsAg and negative anti-HBc IgM within 24 weeks prior to the baseline visit OR at least one positive HBsAg and two positive HBV DNA over a period of greater than or equal to 24 weeks prior to the baseline visit. 4. Presence of HBeAg in serum at the last screening visit within 6 weeks of the baseline visit . 5. Serum HBV DNA level >10(7) IU/mL on at least two occasions at least 12 weeks apart during the 52 weeks before the baseline visit. One of the two HBV DNA levels must be within 6 weeks of the baseline visit. 6. ALT levels persistently less than or equal to 45 U/L in males, less than or equal to 30 U/L in females (approximately 1.5 times the upper limit of normal [ULN] range) as documented by at least three 7. Values: one taken 28-52 weeks before the baseline visit, one taken 6 to 28 weeks before the baseline visit, and the final value within 6 weeks prior to the baseline visit. No evidence of HCC based upon alpha-fetoprotein (AFP) less than or equal to 20 ng/mL at the screening visit (up to 6 weeks prior to the baseline visit): a. Participants who meet AASLD criteria for HCC surveillance must have negative liver imaging as shown by ultrasound (US), computerized tomography (CT) or magnetic resonance imaging (MRI) within 28 weeks prior to the baseline visit as part of standard of care. b. Participants with AFP >20 ng/mL must be evaluated clinically with additional imaging and shown not to have HCC on CT or MRI before they can be enrolled. 8. Provide informed consent and agree to adhere to the requirements of the study. EXCLUSION CRITERIA: 1. History of hepatic decompensation, including but not limited to ascites, variceal bleeding, or hepatic encephalopathy. 2. Evidence of decompensated liver disease prior to or during screening, including direct bilirubin >0.5 mg/dL, INR >1.5, or serum albumin <3.5 g/dL. 3. Platelet count <120,000/mm3, hemoglobin <13 g/dl (males) or <12 g/dl (females), absolute neutrophil count < 1500 /mm3 (<1000/mm3 for African-Americans) at the last screening visit. 4.Previous treatment with medications that have established activity against HBV including, but not limited to, interferon and nucleos(t)ide analogs greater than or equal to 24 weeks. Patients with <24 weeks of prior HBV treatment and a wash-out period >24 weeks are not excluded. Brief and episodic use of famciclovir or valacyclovir for herpes infection is not exclusionary. 5. Known allergy or intolerance to any of the study medications. 6. Females who are pregnant or breastfeeding. 7. Females of childbearing potential unable or unwilling to use a reliable method of contraception during the treatment period. 8. Renal insufficiency with calculated creatinine clearance <50 mL/min at the last screening visit. 9. History of alcohol or drug abuse within 48 weeks of the baseline visit. 10. Previous liver or other organ transplantation including engrafted bone marrow transplant. 11. Any other concomitant liver disease, including hepatitis C or D. Non-alcoholic fatty liver disease (NAFLD) with steatosis and/or mild to moderate steatohepatitis is acceptable but NALFD with severe steatohepatitis is exclusionary. 12. Presence of anti-HDV or anti-HCV (unless HCV RNA negative) in serum on any occasion in the 144 weeks prior to the baseline visit. 13. Presence of anti-HIV (test to be completed within 6 weeks prior to the baseline visit). 14. Pre-existing psychiatric condition(s), including, but not limited to: a. Current moderate or severe depression as determined by the study physician b. History of depression requiring hospitalization within past 10 years c. History of suicidal or homicidal attempt within the past 10 years d. History of severe psychiatric disorders including, but not limited to schizophrenia, psychosis, bipolar disorder as determined by a study physician. 15. History of immune-mediated or cerebrovascular disease, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, poorly controlled diabetes or uncontrolled seizure disorder, as determined by a study physician. 16. Any medical condition that would, in the opinion of a study physician, be predicted to be exacerbated by therapy or that would limit study participation. 17. Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids or other immunosuppressive medications during the course of this study. 18. Evidence of active or suspected malignancy, or a history of malignancy within the 144 weeks prior to the baseline visit (except adequately treated carcinoma in situ or basal cell carcinoma of the skin). 19. Expected need for ongoing use of any antivirals with activity against HBV during the course of the study. 20. Concomitant use of complementary or alternative medications purported to have antiviral activity. 21.Participation in any other clinical trial involving investigational drugs within 30 days of the baseline visit or intention to participate in another clinical trial involving investigational drugs during participation in this study. 22. Any other condition or situation that in the opinion of a study physician would make the participant unsuitable for enrollment or could interfere with the participant participating in and completing the study.
1. Enrolled in the Hepatitis B Research Network (HBRN) Cohort Study or completed the necessary components of the Cohort baseline evaluation by the end of the baseline visit for this study
2. greater than or equal to 18 years of age at the baseline visit (day 0). Patients >50 years of age at the baseline visit need to have a liver biopsy as standard of care with HAI less than or equal to 3 and Ishak fibrosis score less than or equal to 1 within 96 weeks prior to the baseline visit.
3. Documented chronic HBV infection as evidenced by detection of HBsAg in serum for greater than or equal to 24 weeks prior to the baseline visit OR at least one positive HBsAg and negative anti-HBc IgM within 24 weeks prior to the baseline visit OR at least one positive HBsAg and two positive HBV DNA over a period of greater than or equal to 24 weeks prior to the baseline visit.
4. Presence of HBeAg in serum at the last screening visit within 6 weeks of the baseline visit .
5. Serum HBV DNA level >10(7) IU/mL on at least two occasions at least 12 weeks apart during the 52 weeks before the baseline visit. One of the two HBV DNA levels must be within 6 weeks of the baseline visit.
6. ALT levels persistently less than or equal to 45 U/L in males, less than or equal to 30 U/L in females (approximately 1.5 times the upper limit of normal [ULN] range) as documented by at least three
7. Values: one taken 28-52 weeks before the baseline visit, one taken 6 to 28 weeks before the baseline visit, and the final value within 6 weeks prior to the baseline visit. No evidence of HCC based upon alpha-fetoprotein (AFP) less than or equal to 20 ng/mL at the screening visit (up to 6 weeks prior to the baseline visit):
a. Participants who meet AASLD criteria for HCC surveillance must have negative liver imaging as shown by ultrasound (US), computerized tomography (CT) or magnetic resonance imaging (MRI) within 28 weeks prior to the baseline visit as part of standard of care.
b. Participants with AFP >20 ng/mL must be evaluated clinically with additional imaging and shown not to have HCC on CT or MRI before they can be enrolled.
8. Provide informed consent and agree to adhere to the requirements of the study.
EXCLUSION CRITERIA:
1. History of hepatic decompensation, including but not limited to ascites, variceal bleeding, or hepatic encephalopathy.
2. Evidence of decompensated liver disease prior to or during screening, including direct bilirubin >0.5 mg/dL, INR >1.5, or serum albumin <3.5 g/dL.
3. Platelet count <120,000/mm3, hemoglobin <13 g/dl (males) or <12 g/dl (females), absolute neutrophil count < 1500 /mm3 (<1000/mm3 for African-Americans) at the last screening visit.
4.Previous treatment with medications that have established activity against HBV including, but not limited to, interferon and nucleos(t)ide analogs greater than or equal to 24 weeks. Patients with <24 weeks of prior HBV treatment and a wash-out period >24 weeks are not excluded. Brief and episodic use of famciclovir or valacyclovir for herpes infection is not exclusionary.
5. Known allergy or intolerance to any of the study medications.
6. Females who are pregnant or breastfeeding.
7. Females of childbearing potential unable or unwilling to use a reliable method of contraception during the treatment period.
8. Renal insufficiency with calculated creatinine clearance <50 mL/min at the last screening visit.
9. History of alcohol or drug abuse within 48 weeks of the baseline visit.
10. Previous liver or other organ transplantation including engrafted bone marrow transplant.
11. Any other concomitant liver disease, including hepatitis C or D. Non-alcoholic fatty liver disease (NAFLD) with steatosis and/or mild to moderate steatohepatitis is acceptable but NALFD with severe steatohepatitis is exclusionary.
12. Presence of anti-HDV or anti-HCV (unless HCV RNA negative) in serum on any occasion in the 144 weeks prior to the baseline visit.
13. Presence of anti-HIV (test to be completed within 6 weeks prior to the baseline visit).
14. Pre-existing psychiatric condition(s), including, but not limited to:
a. Current moderate or severe depression as determined by the study physician
b. History of depression requiring hospitalization within past 10 years
c. History of suicidal or homicidal attempt within the past 10 years
d. History of severe psychiatric disorders including, but not limited to schizophrenia, psychosis, bipolar disorder as determined by a study physician.
15. History of immune-mediated or cerebrovascular disease, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, poorly controlled diabetes or uncontrolled seizure disorder, as determined by a study physician.
16. Any medical condition that would, in the opinion of a study physician, be predicted to be exacerbated by therapy or that would limit study participation.
17. Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids or other immunosuppressive medications during the course of this study.
18. Evidence of active or suspected malignancy, or a history of malignancy within the 144 weeks prior to the baseline visit (except adequately treated carcinoma in situ or basal cell carcinoma of the skin).
19. Expected need for ongoing use of any antivirals with activity against HBV during the course of the study.
20. Concomitant use of complementary or alternative medications purported to have antiviral activity.
21.Participation in any other clinical trial involving investigational drugs within 30 days of the baseline visit or intention to participate in another clinical trial involving investigational drugs during participation in this study.
22. Any other condition or situation that in the opinion of a study physician would make the participant unsuitable for enrollment or could interfere with the participant participating in and completing the study.
Principal Investigator
Referral Contact
For more information: