A Multi-center, Randomized, Double-Blind, Active-Control, 96 Week, Phase III Trial of the Efficacy and Safety of Clevudine Compared with Adefovir at Weeks 48 and 96 in Nucleoside Treatment-Naïve Patients with HBeAg Negative Chronic Hepatitis due to Hepatitis B Virus

• Conditions: Chronic hepatitis due to hepatitis B virus; MedDRA version: 9.1Level: LLTClassification code 10008910Term: Chronic hepatitis B

• Registration Number: EUCTR2007-001063-30-CZ
• Lead Sponsor: Pharmasset, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-05-23
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 480

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 <12 weeks of alpha interferon, and
c) developed rebound chronic hepatitis B following withdrawal of interferon monotherapy due
to tolerability issues.
4. Subjects who have compensated hepatic function despite chronic hepatitis B infection.
5. HBV DNA = 5.0 log10 (= 10,000) copies/mL using the Roche COBAS Taqman Assay.
6. Subjects must have both:
a) An ALT value > 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 < 2 mg/dL.
11. INR =1.5
12. Serum albumin > 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 <1:320.
17. Normal electrocardiogram (ECG) or clinically non-significant changes at screening.
18. Adequate renal function to take adefovir without any dose modifications; creatinine clearance must
be = 50 mL/min (based on the Cockcroft-Gault equation, see Section 13.5).
19. Able and willing to undergo protocol-specified liver biopsies at Screening and Week 48. Note:
subjects who have had a liver biopsy within six months prior to the baseline visit need not have a
biopsy performed at screening.
20. Able to participate and willing to give written informed consent.
21. Able and willing to comply with study assessments and restrictions.
22. Able and willing to participate in the patient-reported outcomes

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified