- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00823342
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
January 30, 2023 updated by: French National Agency for Research on AIDS and Viral Hepatitis
ANRS HB 05 : A Randomized, Double Blind, 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
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.
Study Overview
Status
Terminated
Study Type
Interventional
Enrollment (Anticipated)
150
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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-
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Marseille, France, 13285
- Hôpital Saint Joseph
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
- Inability or unwillingness to provide informed consent or abide by the requirements of the study Reassessments : If a patient fails to meet the above inclusion /exclusion criteria for a reason thought to be reversible, that patient may be reassessed for entry on two additional occasions at most. If the parameter out of range for inclusion was ALT over 10 x ULN, the patient should be reassessed over 4 weeks after the date corresponding to the value that was over 10 x ULN.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
PLACEBO_COMPARATOR: Group A
CLEVUDINE 30 mg qd + TENOFOVIR Placebo
|
30 MG
|
ACTIVE_COMPARATOR: Group B
TENOFOVIR 300 mg qd in association with CLEVUDINE 30 mg qd
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TENOFOVIR 300 mg qd in association with CLEVUDINE 30 mg qd
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PLACEBO_COMPARATOR: Group C
TENOFOVIR 300 mg qd + CLEVUDINE Placebo
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TENOFOVIR 300 mg qd + CLEVUDINE Placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
Time Frame: At 120 week
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At 120 week
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
Time Frame: At 24 week, 48 week and 96 week
|
At 24 week, 48 week and 96 week
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: MARC BOURLIERE, MD, Hôpital Saint Joseph, marseille, France
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
December 14, 2008
Primary Completion (ACTUAL)
December 14, 2008
Study Completion (ACTUAL)
December 14, 2008
Study Registration Dates
First Submitted
January 14, 2009
First Submitted That Met QC Criteria
January 14, 2009
First Posted (ESTIMATE)
January 15, 2009
Study Record Updates
Last Update Posted (ACTUAL)
January 31, 2023
Last Update Submitted That Met QC Criteria
January 30, 2023
Last Verified
January 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis B
- Hepatitis
- Hepatitis A
- Virus Diseases
- Hepatitis B, Chronic
- Hepatitis, Chronic
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Tenofovir
- Clevudine
Other Study ID Numbers
- 2008-000733-21
- ANRS HB 05
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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