ANRS HB 05 Multicenter Study Evaluating Efficacy and Safety of Clevudine Monotherapy Versus Tenofovir Monotherapy Versus Combination Therapy of Clevudine and Tenofovir for 96 Weeks in HBeAg Negative Patients With Chronic Hepatitis B, naïve to Anti-VHB Therapy

NCT ID: NCT00823342

Last Updated: 2023-01-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-14
• Study Completion Date: 2008-12-14

Brief Summary

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 clearence 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.

Conditions

HBe Negative Chronic Hepatitis B; Hepatitis B Viral Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group A

CLEVUDINE 30 mg qd + TENOFOVIR Placebo

Group Type: PLACEBO_COMPARATOR

CLEVUDINE + TENOFOVIR PLACEBO

Intervention Type: DRUG

30 MG

Group B

TENOFOVIR 300 mg qd in association with CLEVUDINE 30 mg qd

Group Type: ACTIVE_COMPARATOR

CLEVUDINE IN ASSOCIATION TENOFOVIR

Intervention Type: DRUG

TENOFOVIR 300 mg qd in association with CLEVUDINE 30 mg qd

Group C

TENOFOVIR 300 mg qd + CLEVUDINE Placebo

Group Type: PLACEBO_COMPARATOR

TENOFOVIR + CLEVUDINE PLACEBO

Intervention Type: DRUG

TENOFOVIR 300 mg qd + CLEVUDINE Placebo

Interventions

CLEVUDINE + TENOFOVIR PLACEBO

30 MG

Intervention Type: DRUG

CLEVUDINE IN ASSOCIATION TENOFOVIR

TENOFOVIR 300 mg qd in association with CLEVUDINE 30 mg qd

Intervention Type: DRUG

TENOFOVIR + CLEVUDINE PLACEBO

TENOFOVIR 300 mg qd + CLEVUDINE Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and female patients over 18 years of age
• Chronic hepatitis B, HBs Ag-positive for over 6 months, anti HBs negative
• Patients with HBeAg- negative chronic hepatitis B (CHB) and anti-HBe positive at screen
• Patients naïve to anti-HBV nucleoside or nucleotide and any other experimental nucleoside/nucleotide analog for HBV
• Serum HBV-DNA quantifiable over 2000 IU/mL at screening
• ALT over 1.25 ULN and below 10 ULN
• Liver biopsy (baseline or within prior 6 months) with evidence of chronic hepatic inflammatory injury (Metavir Activity score over 1 ; Knodell necroinflammatory score over 3, Ishak score over 1)

Exclusion Criteria

• Cirrhosis or bridging fibrosis on liver biopsy
• Subjects who have received any form of alpha interferon in the past 6 months prior to the first administration of randomized treatment
• Any systemic anti-viral, anti-neoplastic or immuno-modulatory treatment (including supraphysiologic doses of steroids and radiation) below 6 months prior to the first dose of randomized treatment and during the study (except for below 10 days of acyclovir for herpetic lesions, or prednisone below 10 mg/days for below 10 days more than 1 month)
• Women with ongoing pregnancy or breast feeding
• Positive test at screening for anti-HAV IgM Ab, anti-HIV Ab, anti-HCV Ab, HCV RNA, anti-HDV Ab
• 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)
• History or other evidence of bleeding from esophageal varices or other clinical conditions consistent with decompensated liver disease (defined by one of the following criteria being met: serum albumin below 3.5 g/L, prothrombin time over 4 seconds prolonged, serum bilirubin over 34 µmol/L, history of encephalopathy, history of ascites)
• Neutrophil count below 1200 cells/mm3 or platelet count below 90,000 cells/mm3 at screening
• Serum creatinine level over 130µmol/l or calculated creatinine clearance below 70 ml/min (Cockcroft-Gault)
• Evidence or history of tubular nephropathy , Fanconi syndrom or hypophosphoremia.
• Evidence of drug abuse (including excessive alcohol consumption) within one year of study entry
• History of a severe seizure disorder or current anticonvulsant use
• History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis etc.)
• History of major organ transplantation with an existing functional graft
• History or other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
• Evidence of an active or suspected cancer or a history of malignancy where the risk of recurrence is over 20 % within 2 years
• Patients with a value of alpha-fetoprotein over 100 ng/mL are excluded, unless stability (less than 10 % increase) has been documented over at least the previous 3 months
• Patients included in another trial within 8 weeks prior to screening

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

Pharmasset

INDUSTRY

Sponsor Role: collaborator

French National Agency for Research on AIDS and Viral Hepatitis

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MARC BOURLIERE, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint Joseph, marseille, France

Locations

Hôpital Saint Joseph

Marseille, , France

Countries

France

Other Identifiers

ANRS HB 05

Identifier Type: -

Identifier Source: secondary_id

2008-000733-21

Identifier Type: -

Identifier Source: org_study_id