HBe Negative Chronic Hepatitis BPhase 3NCT00823342
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
A Phase 3 study testing CLEVUDINE IN ASSOCIATION TENOFOVIR in people with HBe Negative Chronic Hepatitis B and Hepatitis B Viral Infection, run by French National Agency for Research on AIDS and Viral Hepatitis at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HBe Negative Chronic Hepatitis B, Hepatitis B Viral Infection
- What is being tested?
- CLEVUDINE IN ASSOCIATION TENOFOVIR
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteFrance
- Study dates
- 14 Dec 2008to 14 Dec 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Being tested
- CLEVUDINE + TENOFOVIR PLACEBO, CLEVUDINE IN ASSOCIATION TENOFOVIR, TENOFOVIR + CLEVUDINE PLACEBO
- Keywords
- HBe, Hepatitis, Vireda (TENOFOVIR, CLEVUDINE), HBV, HBe Ag negative
- Medical subject headings
- Hepatitis, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CLEVUDINE + TENOFOVIR PLACEBODrug
30 MG
CLEVUDINE IN ASSOCIATION TENOFOVIRDrug
TENOFOVIR 300 mg qd in association with CLEVUDINE 30 mg qd
TENOFOVIR + CLEVUDINE PLACEBODrug
TENOFOVIR 300 mg qd + CLEVUDINE Placebo
| Study group | Role | What they receive |
|---|---|---|
| Group A | Placebo comparator | CLEVUDINE 30 mg qd + TENOFOVIR Placebo Receives: Drug: CLEVUDINE + TENOFOVIR PLACEBO |
| Group B | Active comparator | TENOFOVIR 300 mg qd in association with CLEVUDINE 30 mg qd Receives: Drug: CLEVUDINE IN ASSOCIATION TENOFOVIR |
| Group C | Placebo comparator | TENOFOVIR 300 mg qd + CLEVUDINE Placebo Receives: Drug: TENOFOVIR + CLEVUDINE PLACEBO |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: At 24 week, 48 week and 96 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2009 (estimated)
- Study start14 Dec 2008
- Primary completion14 Dec 2008
- Study completion14 Dec 2008
Why it stopped: safety aspects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HBe Negative Chronic Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- French National Agency for Research on AIDS and Viral Hepatitis
- Sponsor type
- Other government
- Collaborators
- Gilead Sciences, Pharmasset
- Responsible party
- Sponsor
- Investigators
- MARC BOURLIERE, MD, Principal investigator, Hôpital Saint Joseph, marseille, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00823342
- Sponsor's protocol ID
- ANRS HB 05 CLEVUDINE
- Other IDs
- 2008-000733-21, 2008
- Status last verified
- Jan 2023
- First submitted
- 14 Jan 2009
- Last updated
- 6 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00823342
- Acronym / sponsor ID
- ANRS HB 05 CLEVUDINE
- Keywords
- HBe, Hepatitis, Vireda (TENOFOVIR, CLEVUDINE), HBV, HBe Ag negative
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: safety aspects
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- French National Agency for Research on AIDS and Viral HepatitisOther government
- Collaborators
- Gilead Sciences, Pharmasset
- Study start
- 14 Dec 2008 (actual)
- Primary completion
- 14 Dec 2008 (actual)
- Study completion
- 14 Dec 2008 (actual)
- First posted
- 15 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A | Placebo comparator | Drug: CLEVUDINE + TENOFOVIR PLACEBOCLEVUDINE 30 mg qd + TENOFOVIR Placebo |
| Group B | Active comparator | Drug: CLEVUDINE IN ASSOCIATION TENOFOVIRTENOFOVIR 300 mg qd in association with CLEVUDINE 30 mg qd |
| Group C | Placebo comparator | Drug: TENOFOVIR + CLEVUDINE PLACEBOTENOFOVIR 300 mg qd + CLEVUDINE Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CLEVUDINE + TENOFOVIR PLACEBO30 MG | Drug | Group A |
| CLEVUDINE IN ASSOCIATION TENOFOVIRTENOFOVIR 300 mg qd in association with CLEVUDINE 30 mg qd | Drug | Group B |
| TENOFOVIR + CLEVUDINE PLACEBOTENOFOVIR 300 mg qd + CLEVUDINE Placebo | Drug | Group C |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study was stopped early (reason given: safety aspects). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2026.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MARC BOURLIERE, MD principal investigator
Hôpital Saint Joseph, marseille, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CLEVUDINE IN ASSOCIATION TENOFOVIR in people with HBe Negative Chronic Hepatitis B and Hepatitis B Viral Infection, run by French National Agency for Research on AIDS and Viral Hepatitis at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: safety aspects). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2026.