Chronic hepatitis due to hepatitis B virus MedDRA version: 9.1 Level: LLT Classification code 10008910 Term: Chronic hepatitis B
Conditions
Sponsors
Pharmasset, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or non-pregnant and non-lactating female subjects who are 16 years of age or older (or the legal age of consent as allowed by local regulations). There is no upper age limit imposed. The investigator should consider the individual risk/benefit assessment with the subject before considering elderly subjects eligible. 2. Female subjects may be enrolled if they are: a) Surgically sterile, or b) Using a reliable and appropriate contraceptive method (see Section 11.4), and must be c) Negative for a serum pregnancy test, or d) Post-menopausal (amenorrhea >1 year; they may be enrolled with an FSH test result of > 30 IU/L, without the need for a serum pregnancy test). Subjects diagnosed with chronic hepatitis B. 3. Subjects who have received previous monotherapy treatment with any form of alpha interferon must have: a) ceased alpha interferon monotherapy at least 12 months prior to the baseline visit, and b) received 1.0X ULN and = 10X ULN; and b) One additional documented elevated ALT value within the range of > 1.0X ULN and = 10X ULN, dated less than 6 months prior to baseline. 7. HBsAg+ or other lab evidence of HBV infection dated more than 6 months prior to baseline. 8. Absence of HBeAg. 9. Current liver biopsy (or a historical biopsy obtained within 6 months prior to baseline) with evidence of chronic hepatic inflammatory injury at screening (equivalent to a Knodell HAI grade = 4 and modified Ishak fibrosis score = 5). 10. Total bilirubin of 3 g/dL. 13. Platelet count > 90,000 /mm3. 14. Absolute neutrophil count > 1200 /mm3. 15. Hepatic ultrasound or MRI/CT within the last 6 months without evidence of hepatocellular carcinoma. 16. ANA titer =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects who are coinfected with HIV, HCV or HDV. Note: Although subjects with anti-HCV antibodies who have responded to previous antiviral treatment may be considered cured of chronic hepatitis C infection and have no circulating HCV RNA, these subjects are not eligible for this trial. 2. Previous or current treatment with antivirals, including approved and investigational nucleosides/nucleotides (e.g., lamivudine, adefovir, entecavir, lobucavir, famciclovir, tenofovir, telbivudine) for any duration. 3. Other chronic hepatic disease (e.g., chronic alcoholism, Wilson’s disease) by medical history OR significant non-alcoholic steatohepatitis or other pathology on liver biopsy that is significant enough to interfere with the ability to detect improvement of necroinflammation due to chronic hepatitis B infection. 4. Subjects with a history of ascites, variceal hemorrhage, hepatic encephalopathy, or other conditions consistent with decompensated liver disease. 5. History of lactic acidosis. 6. Concurrent use of nephrotoxic agents (e.g., aminoglycosides, amphotericin B, vancomycin, foscarnet, cisplatinum, pentamidine, cyclosporine, tacrolimus) or competitors of renal tubular excretion (e.g., probenecid) within 60 days prior to study screening or the expectation that the subject will receive these medications during the course of the study. 7. Poorly controlled Type 1 or Type 2 diabetes mellitus (fasting blood glucose > 300 mg/dL and/or HbA1c = 8) within 3 months prior to screening. 8. Severe chronic disease or immunocompromised subjects (including bone marrow and organ transplant subjects). 9. History of pancreatitis (other than an episode related to a documented gallstone followed by cholecystectomy, without complications of pseudocyst, etc.). 10. Use of systemic corticosteroids, or other immunomodulatory agents, including Prednisone >10 mg/day within 30 days of baseline or the expectation that the subject will receive these medications during the course of the study. 11. Significant chronic gastrointestinal (e.g., malabsorption syndrome) or bronchopulmonary disease (e.g., emphysema) requiring chronic therapy. 12. History or evidence of severe cardiac disease (e.g., NYHA Functional Class III or IV; see Appendix B), myocardial infarction within 6 months prior to baseline, ventricular tachyarrythmias requiring ongoing treatment or unstable angina. 13. Malignancy diagnosed or treated within the past 5 years except for squamous cell carcinoma or basal cell carcinoma and those presenting no limitation to cancer-free survival. 14. Any medical, severe psychiatric, occupational, or social condition (including alcohol and drug abuse) currently or within 1 year prior to screening that, in the judgment of the investigator, would interfere with, or serve as a contraindication to protocol adherence, assessment of safety or treatment compliance, or a participant's ability to give informed consent (See Appendix A for alcohol abuse criteria.). Severe psychiatric condition is defined as major depression or psychosis, suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease. 15. Participation in a clinical trial or receipt of an investigational agent, for any reason, within 60 days of baseline. 16. Known serious allergies to nucleoside/nucleotide analogs, including adefovir or clevudine. 17. Donation or loss of more than 400 mL blood within 60 days prior to anticipated baseline visit. 18. Sub
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary efficacy endpoint is the composite response rate defined as the proportion of subjects with both serum HBV DNA <300 copies/mL and normalized ALT at Week 48.;Main Objective: To compare, in nucleoside treatment-naïve subjects with chronic HBeAg- HBV infection, the efficacy of clevudine 30 mg once daily and adefovir 10 mg once daily, each as monotherapy, by assessing the proportion of subjects with serum HBV DNA levels (<300 copies/mL) and ALT normalization at 48 weeks.;Secondary Objective: The secondary objectives characterize other aspects of the subjects’ responses to treatment. Comparisons will be made between the clevudine 30 mg once daily and adefovir 10 mg once daily treatment groups. These secondary objectives are: • To provide supportive efficacy characterization of the primary objective through the use of histological, virological, and biochemical responses at different times throughout the study; • To assess the safety and tolerability of the study treatments; and • To investigate the pharmacokinetics of clevudine in patients. The objectives of the non-responder option are to: • Provide an on-study treatment option for subjects who met criteria for treatment failure in spite of their adherence with the requirements and procedures of the blinded portion of Study 306; • Explore the safety and efficacy and obtain pharmacokinetic data on clevudine used in combination with another locally approved antiviral drug with established activity against HBV | — |
Countries
Czech Republic, Greece, Spain, United Kingdom
Outcome results
None listed