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

NCT00823342 | Terminated Phase 3 DMC

• 2 other identifiers: 2008-000733-21ANRS HB 05
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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

Keywords

HBe, Hepatitis, Vireda (TENOFOVIR, CLEVUDINE), HBV, HBe Ag negative

Outcome Measures

Primary Outcomes (1)

• Compare the long term efficacy of new anti-HBV strategies of CLV monotherapy VS TDF monotherapy VS the combination of CLV + TDF for 96 weeks in HBeAg negative patients with CHB, naïve to anti-HBV-therapy, at 24 weeks post-treatment

  At 120 week

Secondary Outcomes (1)

• 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, percept

  At 24 week, 48 week and 96 week

Study Arms (3)

Group A

PLACEBO COMPARATOR

CLEVUDINE 30 mg qd + TENOFOVIR Placebo

Drug: CLEVUDINE + TENOFOVIR PLACEBO

Group B

ACTIVE COMPARATOR

TENOFOVIR 300 mg qd in association with CLEVUDINE 30 mg qd

Drug: CLEVUDINE IN ASSOCIATION TENOFOVIR

Group C

PLACEBO COMPARATOR

TENOFOVIR 300 mg qd + CLEVUDINE Placebo

Drug: TENOFOVIR + CLEVUDINE PLACEBO

Interventions

CLEVUDINE + TENOFOVIR PLACEBO DRUG

30 MG

Group A

CLEVUDINE IN ASSOCIATION TENOFOVIR DRUG

TENOFOVIR 300 mg qd in association with CLEVUDINE 30 mg qd

Group B

TENOFOVIR + CLEVUDINE PLACEBO DRUG

TENOFOVIR 300 mg qd + CLEVUDINE Placebo

Group C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• French National Agency for Research on AIDS and Viral Hepatitis: lead
• Gilead Sciences: collaborator
• Pharmasset: collaborator

Study Sites (1)

Hôpital Saint Joseph

Marseille, 13285, France

Location

MeSH Terms

Conditions

Hepatitis; Hepatitis B

Interventions

clevudine; Tenofovir

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• MARC BOURLIERE, MD

  Hôpital Saint Joseph, marseille, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2009
• First Posted: January 15, 2009
• Study Start: December 14, 2008
• Primary Completion: December 14, 2008
• Study Completion: December 14, 2008
• Last Updated: January 31, 2023

Record last verified: 2023-01

Locations

FR (1)