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

This study has been terminated.
Sponsor:
Collaborators:
Gilead Sciences
Pharmasset
Information provided by:
French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:
NCT00823342
First received: January 14, 2009
Last updated: May 7, 2009
Last verified: May 2009
  Purpose

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.


Condition Intervention Phase
HBe Negative Chronic Hepatitis B
Hepatitis B Viral Infection
Drug: CLEVUDINE + TENOFOVIR PLACEBO
Drug: CLEVUDINE IN ASSOCIATION TENOFOVIR
Drug: TENOFOVIR + CLEVUDINE PLACEBO
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 150
Study Start Date: December 2008
Estimated Study Completion Date: September 2011
Estimated Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Group A
CLEVUDINE 30 mg qd + TENOFOVIR Placebo
Drug: CLEVUDINE + TENOFOVIR PLACEBO
30 MG
Active Comparator: Group B
TENOFOVIR 300 mg qd in association with CLEVUDINE 30 mg qd
Drug: CLEVUDINE IN ASSOCIATION TENOFOVIR
TENOFOVIR 300 mg qd in association with CLEVUDINE 30 mg qd
Placebo Comparator: Group C
TENOFOVIR 300 mg qd + CLEVUDINE Placebo
Drug: TENOFOVIR + CLEVUDINE PLACEBO
TENOFOVIR 300 mg qd + CLEVUDINE Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00823342

Locations
France
Hôpital Saint Joseph
Marseille, France, 13285
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Gilead Sciences
Pharmasset
Investigators
Principal Investigator: MARC BOURLIERE, MD Hôpital Saint Joseph, marseille, France
  More Information

No publications provided

Responsible Party: Karim Kaabeche/regulatory affairs, ANRS
ClinicalTrials.gov Identifier: NCT00823342     History of Changes
Other Study ID Numbers: 2008-000733-21, ANRS HB 05
Study First Received: January 14, 2009
Last Updated: May 7, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:
HBe, Hepatitis, Vireda (TENOFOVIR, CLEVUDINE), HBV, HBe Ag negative

Additional relevant MeSH terms:
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Hepatitis A
Hepatitis, Chronic
Virus Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Clevudine
Tenofovir
Tenofovir disoproxil
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 14, 2014