Response and markers of response in chronic hepatitis B patients treated with peg-interferon alfa-2a and adefovir

Not Applicable

Completed

Conditions: Chronic Hepatitis B Virus (HBV)
Infections and Infestations
Hepatitis B

Registration Number: ISRCTN77073364

Lead Sponsor: Academic Medical Center (AMC) (The Netherlands)

Brief Summary: 2011 Results article in http://www.ncbi.nlm.nih.gov/pubmed/21557773 results 2017 Results article in http://www.ncbi.nlm.nih.gov/pubmed/28632898 results 2021 Results article in https://pubmed.ncbi.nlm.nih.gov/34583061/ results (added 29/09/2021)

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 92

Inclusion Criteria

1. Male and female patients over 18 years of age
2. Positive Hepatitis B surface Antigens (HBsAg) for more than six months
3. a. for Hepatitis B 'e' Antigen (HBeAg) positive patients: HBeAg positive, anti-HBe negative and Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) more than 100,000 cop/mL (more than 17,000 IU/mL) as measured by Polymerase Chain Reaction (PCR)
b. for HBeAg negative patients: HBeAg negative for more than six months, and anti-HBeAg positive, HBV DNA (more than 100,000 cop/mL [more than 17,000 IU/mL]) as measured by PCR
4. Patients with Chronic Hepatitis B (CHB) who are either naÏve to HBV treatment, or have received and have not responded/relapsed to either conventional Interferon (IFN) or Lamivudine (LAM) in the past
5. If the patient has used LAM, the patient must have been on LAM for a period of at least six months
6. Elevated serum Alanine Aminotransferase (ALAT) more than Upper Limit of Normal (ULN) but less than or equal to 10 x ULN as determined by two abnormal values taken more than 14 days apart during the six months before the first dose of study drug with at least one of the determinations obtained during the screening period
7. A liver biopsy obtained at a maximum of one year prior to study enrollment, demonstrating liver disease consistent with chronic hepatitis B and/or more than fibrosis stage 2 (Ishak classification). Patients with cirrhosis or marked fibrosis on liver biopsy must also have a liver imaging study to rule out hepatic carcinoma.

Exclusion Criteria

1. Patients co-infected with Hepatitis C Virus (HCV), Hepatitis D Virus (HDV), Human Immunodeficiency Virus (HIV) or who have decompensated liver disease, hepato-cellular carcinoma, pre-existing severe depression or other psychiatric disease, significant cardiac disease, significant renal disease, seizure disorders or severe retinopathy will be excluded
2. Patients who have received LAM therapy for their chronic hepatitis B within six weeks before enrolment or any other antiviral therapy for their chronic hepatitis B within six months before enrolment (e.g. IFN)
3. Patients must not have received any other systemic anti-viral, anti-neoplastic or immuno-modulatory treatment (including supraphysiologic doses of steroids or radiation)
4. Positive test at screening for anti-Hepatitis A Virus Immunoglobulin M (HAV IgM), anti-HIV, anti-HCV, HCV Ribonucleic Acid (RNA) or anti-HDV
5. Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded.
Exception: patients who have had a limited (less than or equal to seven day) course of acyclovir for herpetic lesions more than one month prior to the first administration of test drug are not excluded
6. Evidence of decompensated liver disease (Child B-C)
7. Serum total bilirubin more than twice the upper limit of normal at screening
8. History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
9. History or other evidence of a medical condition associated with chronic liver disease other than HBV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver diseases including Wilson?s disease and alfa1-antitrypsin deficiency, alcoholic liver disease, toxin exposures, thalassemia)
10. Women with ongoing pregnancy or who are breast feeding
11. Neutrophil count less than 1500 cells/mm^3 or platelet count less than 90,000 cells/mm^3 at screening
12. Hemoglobin less than 7.1 mmol/L (less than 11.5 g/dL) for females and less than 7.8 mmol/L (less than 12.5 g/dL) for men at screening
13. Serum creatinine level more than 1.5 times the ULN at screening
14. History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as major depression or psychosis, a period of treatment with an antidepressant medication or major tranquiliser at therapeutic doses for depression or psychosis for at least three months, a suicidal attempt, hospitalisation for psychiatric disease, or a period of disability due to a psychiatric disease
15. History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis)
16. History or other evidence of chronic pulmonary disease associated with functional limitation. Severe cardiac disease (e.g., New York Heart Association [NYHA] Functional Class III or IV, myocardial infarction within six months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases)
17. History of a severe seizure disorder

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To establish the rate of response (HBV-DNA levels less than 100,000 cop/mL [17,000 IU/mL]) at end of follow-up and to determine if markers at base line and early during treatment can predict response.

Secondary Outcome Measures

Name	Time	Method
<br> 1. To establish rate of response at levels HBV-DNA less than 10,000 cop/mL (1,700 IU/mL), less than 400 cop/mL (72 IU/mL) and at limit of detection (less than 300 cop/mL [54 IU/mL]) at end of follow-up.<br> 2. To establish predictive markers for response of primary and secondary end points.<br> 3. To establish the rate of HBeAg seroconversion at end of follow-up in HBeAg positive patients only.<br>

Related Trials