For chronic HBV infection, an optimal pharmacological agent to promote recovery from chronic HBV infection would be one that inhibits HBV DNA polymerase, combined with the clearance from the liver of cccDNA to block HBV reactivation after the circulating viral burden has been eliminated by therapy The activity of clevudine on cccDNA in combination with its potent antiviral activity on HBV polymerase makes it the optimal agent in combination with tenofovir for this protocol. MedDRA version: 9.1
Conditions
Interventions
Product Name: Clevudine
Product Code: PSI-5268
Pharmaceutical Form: Capsule*
INN or Proposed INN: Clevudine
CAS Number: 163252-36-6
Current Sponsor code: PSI-5268
Other descriptive name: L-FMAU, LFMAU
Sponsors
ANRS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria 1. Male and female patients ? 18 years of age 2. Chronic hepatitis B, HBs Ag-positive for ? 6 months, anti HBs negative 3. Patients with HBeAg- negative chronic hepatitis B (CHB) and anti HBe positive at screen 4. Patients naïve to anti-HBV nucleoside or nucleotide therapy and any other experimental nucleoside/nucleotide analog for HBV 5. Serum HBV-DNA quantifiable at ? 2000 IU/mL at screening 6. ALT = 1.25 ULN and = 10 ULN 7. Liver biopsy (baseline or within prior 6 months) with evidence of chronic hepatic inflammatory injury (Metavir Activity score = 1, Knodell necroinflammatory score = 3, Ishak score = 1) Are the trial subjects under 18? no 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
Exclusion criteria: 1. Cirrhosis or bridging fibrosis on liver fibrosis 2. Subjects who have received any form of alpha interferon in the past 6 months prior to the first administration of randomized treatment 3. Any systemic anti-viral, anti-neoplastic or immuno-modulatory treatment (including supraphysiologic doses of steroids and radiation) ? 6 months prior to the first dose of randomized treatment and during the study (except for ? 10 days of acyclovir for herpetic lesions, or prednisone = 10 mg/days for = 10 days more than 1 month) 4. Women with ongoing pregnancy or breast feeding 5. Positive test at screening for anti-HAV IgM Ab, anti-HIV Ab, anti-HCV Ab, HCV RNA, anti-HDV Ab 6. History or other evidence of a medical condition associated with chronic liver disease other than HBV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease including Wilson’s disease and alpha1-antitrypsin deficiency, alcoholic liver disease, toxin exposures, toxic thalassemia, NASH) 7. History or other evidence of bleeding from oesophageal varices or other clinical conditions consistent with decompensated liver disease (defined by one of the following criteria being met : serum albumin 4 seconds prolonged, serum bilirubin > 34 µmol/L, history of encephalopathy, history of ascites) 8. Neutrophil count 130µmol/l or calculated creatinine clearance 100 ng/mL are excluded, unless stability (less than 10 % increase) has been documented over at least the previous 3 months 18. Patients included in another trial within 8 weeks prior to screening 19. Inability or unwillingness to provide informed consent or abide by the requirements of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective To compare the long term efficacy of new anti-HBV strategies of CLV monotherapy versus TDF monotherapy versus the combination of CLV + TDF for 96 weeks in HBeAg negative patients with CHB, naïve to anti-HBV-therapy, at 24 weeks post-treatment. ;Secondary Objective: Secondary Objectives To compare the safety profile of CLV + TDF compared to that of CLV and TDF in HBeAg negative patients with CHB, naïve to anti-HBV-therapy. To compare perceived toxicity as expressed by the nature and the number of self-reported side effects and perception of fatigue impact on physical, cognitive and psychosocial functioning. ;Primary end point(s): Primary Endpoints Proportion of patients with HBV DNA <50 IU/mL using the Roche TaqMan® Assay at 24 weeks following cessation of 96 Weeks of study treatment. | — |
Countries
France
Outcome results
None listed