Chronic Hepatitis BPhase 1/2VAC-ADNNCT00536627
Efficacy and Tolerance of Naked DNA Vaccine in Patients With Chronic B Hepatitis
A Phase 1/2 study testing DNA vaccine pCMVS2.S in people with Chronic Hepatitis B, run by French National Agency for Research on AIDS and Viral Hepatitis at 1 site in France.
Trial summary
The purpose of this study is to determine if DNA vaccination of chronic HBV patients under treatment with NRTI can restore T-cell responsiveness and delay virologic reactivation after treatment discontinuation. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- DNA vaccine pCMVS2.S
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2008to Nov 2010
- Phase
- Phase 1/2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- chronic hepatitis B with or without AgHBe
- no cirrhosis and no hepatocellular carcinoma
- treatment with NRTI unchanged for at least 3 months
- undetectable HBV viral load for 12 months
- HBV viral load < 12 IU/ml at screening
- sGPT < 5N
Show all 10Show fewer
- tetanus immunization or booster dose for less than 8 years
- accurate birth control or menopausal women or sterility
- sickness insurance
- signed informed consent
Who cannot join
- HLA-DR 15/16
- coinfections with HDV, HCV and/or HIV
- treatment with immunomodulators
- immunosuppressors
- long-term corticotherapy (over 4 weeks)
- active intravenous drug-users
Show all 14Show fewer
- prolonged and excessive consumption of alcohol (men > 40g/day ; women > 30g/day ; for more than 5 years)
- medical history of autoimmune disease or presence of autoantibodies
- previous immunization by HBV vaccine of less than 5 years
- previous immunization by DNA vaccine against HBV
- personal or family medical history of demyelinising diseases
- uncontrolled hypophosphatemia
- renal failure, renal transplantation, haemodialysis
- pregnancy, breast-feeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomised, Opened, Multicentre Phase I/II Trial in Patients With Chronic Hepatitis B With HBV VL < 12 IU/ml and Under Treatment With NRTI, Which Evaluated Efficacy and Tolerance of Vaccination With Naked DNA on Viral Replication After Analogs' Treatment Interruption. ANRS HB02 VAC-ADN
The purpose of this study is to determine if DNA vaccination of chronic HBV patients under treatment with NRTI can restore T-cell responsiveness and delay virologic reactivation after treatment discontinuation.
Read the detailed description
Despite the availability of effective vaccines against hepatitis B, over 370 million people worldwide remain persistently infected with HBV. Persistent infection is associated with chronic liver disease that can lead to the developement of cirrhosis and hepatocellular carcinoma in two-third of persons. Treatment of chronic hepatitis B relies on the use of analogs such as lamivudine, adefovir, entecavir or immunostimulators such as interferons. Although analogs are efficient, genotypic resistance occurs after one year of treatment and the rate of virologic relapse is high after treatment discontinuation.
HBV is a non cytopathic virus and liver damage is caused by immune response against infected hepatocytes and to a non specific inflammatory response. Immune response contributes to the virus clearance. In acute hepatitis B infection, T cell response is polyclonal, specific and vigorous, whereas in patients with chronic infection, responses remain weak, less specific and hardly detectable in peripheral blood.
T cell responses could be induced or restored by antigenic stimulation such as vaccination. In a previous phase I clinical trial, we showed that DNA vaccination with plasmid pCMVS2.S is safe and can specifically, but transiently activate T-cell responses in chronic HBV-carriers not responding to current antiviral therapies.
Analogs such as lamivudine and adefovir were shown to enhance T cell responses concomitantly with viral load decrease. In this phase I/II clinical trial, we would like to determine if DNA vaccination of chronic HBV patients under treatment with NRTI can restore T-cell responsiveness and delay virologic reactivation after treatment discontinuation.
- Conditions
- Chronic Hepatitis B
- Being tested
- DNA vaccine pCMVS2.S
- Keywords
- DNA vaccine
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNA vaccine pCMVS2.SBiological
Patients will receive injections of 1 ml of vaccine (1 mg/ml) at weeks 0, 8, 16, 40 and 44
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Patients will receive 5 injections of DNA vaccine at weeks 0, 8, 16, 40, 44. Receives: Biological: DNA vaccine pCMVS2.S |
| 2 | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary endpoint is virologic failure defined by 1) reactivation after analogs' treatment interruption, 2) virologic breakthrough during treatment with analogs, 3) the impossibility for the patients to interrupt treatment at week 48
Measured: at week 72
Secondary outcomes (4)
Delay of appearance of virologic failure
Measured: at Week 72
Biological and clinical tolerance of DNA vaccine
Measured: all along the trial
Immunological responses
Measured: At weeks 18, 40, 46, 60, 72
Clinical progression of hepatitis B
Measured: all along the trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2007 (estimated)
- Study startJan 2008
- Primary completionNov 2010
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- French National Agency for Research on AIDS and Viral Hepatitis
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Hélène FONTAINE, MD, Principal investigator, Pôle d'Hépatologie, Hôpital COCHIN, PARIS, FRANCEJean-Pierre ABOULKER, MD, Study chair, INSERM SC-10, VILLEJUIF, FRANCE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00536627
- Sponsor's protocol ID
- ANRS HB02 VAC-ADN
- Other IDs
- 2007-001682-15
- Acronym
- VAC-ADN
- Status last verified
- Dec 2011
- First submitted
- 26 Sep 2007
- Last updated
- 2 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mancini-Bourgine M, Fontaine H, Brechot C, Pol S, Michel ML. Immunogenicity of a hepatitis B DNA vaccine administered to chronic HBV carriers. Vaccine. 2006 May 22;24(21):4482-9. doi: 10.1016/j.vaccine.2005.08.013. Epub 2005 Aug 18.
PubMed 16310901Mancini-Bourgine M, Fontaine H, Scott-Algara D, Pol S, Brechot C, Michel ML. Induction or expansion of T-cell responses by a hepatitis B DNA vaccine administered to chronic HBV carriers. Hepatology. 2004 Oct;40(4):874-82. doi: 10.1002/hep.20408.
PubMed 15382173Fontaine H, Kahi S, Chazallon C, Bourgine M, Varaut A, Buffet C, Godon O, Meritet JF, Saidi Y, Michel ML, Scott-Algara D, Aboulker JP, Pol S; ANRS HB02 study group. Anti-HBV DNA vaccination does not prevent relapse after discontinuation of analogues in the treatment of chronic hepatitis B: a randomised trial--ANRS HB02 VAC-ADN. Gut. 2015 Jan;64(1):139-47. doi: 10.1136/gutjnl-2013-305707. Epub 2014 Feb 20.
PubMed 24555998Godon O, Fontaine H, Kahi S, Meritet JF, Scott-Algara D, Pol S, Michel ML, Bourgine M; ANRS HB02 study group. Immunological and antiviral responses after therapeutic DNA immunization in chronic hepatitis B patients efficiently treated by analogues. Mol Ther. 2014 Mar;22(3):675-684. doi: 10.1038/mt.2013.274. Epub 2013 Dec 5.
PubMed 24394187
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised, Opened, Multicentre Phase I/II Trial in Patients With Chronic Hepatitis B With HBV VL < 12 IU/ml and Under Treatment With NRTI, Which Evaluated Efficacy and Tolerance of Vaccination With Naked DNA on Viral Replication After Analogs' Treatment Interruption. ANRS HB02 VAC-ADN
- ClinicalTrials.gov ID
- NCT00536627
- Acronym / sponsor ID
- VAC-ADN / ANRS HB02 VAC-ADN
- Conditions
- Chronic Hepatitis B
- Keywords
- DNA vaccine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- French National Agency for Research on AIDS and Viral HepatitisOther government
- Study start
- Jan 2008
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 28 Sep 2007 (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.
The purpose of this study is to determine if DNA vaccination of chronic HBV patients under treatment with NRTI can restore T-cell responsiveness and delay virologic reactivation after treatment discontinuation.
Detailed description
Despite the availability of effective vaccines against hepatitis B, over 370 million people worldwide remain persistently infected with HBV. Persistent infection is associated with chronic liver disease that can lead to the developement of cirrhosis and hepatocellular carcinoma in two-third of persons. Treatment of chronic hepatitis B relies on the use of analogs such as lamivudine, adefovir, entecavir or immunostimulators such as interferons. Although analogs are efficient, genotypic resistance occurs after one year of treatment and the rate of virologic relapse is high after treatment discontinuation.
HBV is a non cytopathic virus and liver damage is caused by immune response against infected hepatocytes and to a non specific inflammatory response. Immune response contributes to the virus clearance. In acute hepatitis B infection, T cell response is polyclonal, specific and vigorous, whereas in patients with chronic infection, responses remain weak, less specific and hardly detectable in peripheral blood.
T cell responses could be induced or restored by antigenic stimulation such as vaccination. In a previous phase I clinical trial, we showed that DNA vaccination with plasmid pCMVS2.S is safe and can specifically, but transiently activate T-cell responses in chronic HBV-carriers not responding to current antiviral therapies.
Analogs such as lamivudine and adefovir were shown to enhance T cell responses concomitantly with viral load decrease. In this phase I/II clinical trial, we would like to determine if DNA vaccination of chronic HBV patients under treatment with NRTI can restore T-cell responsiveness and delay virologic reactivation after treatment discontinuation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: DNA vaccine pCMVS2.SPatients will receive 5 injections of DNA vaccine at weeks 0, 8, 16, 40, 44. |
| 2 | No intervention | – |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- chronic hepatitis B with or without AgHBe
- no cirrhosis and no hepatocellular carcinoma
- treatment with NRTI unchanged for at least 3 months
- undetectable HBV viral load for 12 months
- HBV viral load < 12 IU/ml at screening
Key exclusion criteria (14 listed)
- HLA-DR 15/16
- coinfections with HDV, HCV and/or HIV
- treatment with immunomodulators
- immunosuppressors
- long-term corticotherapy (over 4 weeks)
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 |
|---|---|---|
| DNA vaccine pCMVS2.SPatients will receive injections of 1 ml of vaccine (1 mg/ml) at weeks 0, 8, 16, 40 and 44 | Biological | 1 |
Primary outcome
Primary endpoint is virologic failure defined by 1) reactivation after analogs' treatment interruption, 2) virologic breakthrough during treatment with analogs, 3) the impossibility for the patients to interrupt treatment at week 48
Time frame: at week 72
4 secondary outcomes
Delay of appearance of virologic failure
Time frame: at Week 72
Biological and clinical tolerance of DNA vaccine
Time frame: all along the trial
Immunological responses
Time frame: At weeks 18, 40, 46, 60, 72
Clinical progression of hepatitis B
Time frame: all along the trial
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
- Background: PubMed 16310901Mancini-Bourgine M, Fontaine H, Brechot C, Pol S, Michel ML. Immunogenicity of a hepatitis B DNA vaccine administered to chronic HBV carriers. Vaccine. 2006 May 22;24(21):4482-9. doi: 10.1016/j.vaccine.2005.08.013. Epub 2005 Aug 18.
- Background: PubMed 15382173Mancini-Bourgine M, Fontaine H, Scott-Algara D, Pol S, Brechot C, Michel ML. Induction or expansion of T-cell responses by a hepatitis B DNA vaccine administered to chronic HBV carriers. Hepatology. 2004 Oct;40(4):874-82. doi: 10.1002/hep.20408.
- Derived from this study: PubMed 24555998Fontaine H, Kahi S, Chazallon C, Bourgine M, Varaut A, Buffet C, Godon O, Meritet JF, Saidi Y, Michel ML, Scott-Algara D, Aboulker JP, Pol S; ANRS HB02 study group. Anti-HBV DNA vaccination does not prevent relapse after discontinuation of analogues in the treatment of chronic hepatitis B: a randomised trial--ANRS HB02 VAC-ADN. Gut. 2015 Jan;64(1):139-47. doi: 10.1136/gutjnl-2013-305707. Epub 2014 Feb 20.
- Derived from this study: PubMed 24394187Godon O, Fontaine H, Kahi S, Meritet JF, Scott-Algara D, Pol S, Michel ML, Bourgine M; ANRS HB02 study group. Immunological and antiviral responses after therapeutic DNA immunization in chronic hepatitis B patients efficiently treated by analogues. Mol Ther. 2014 Mar;22(3):675-684. doi: 10.1038/mt.2013.274. Epub 2013 Dec 5.
Related trials for Chronic Hepatitis B
Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B
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.
Hélène FONTAINE, MD principal investigator
Pôle d'Hépatologie, Hôpital COCHIN, PARIS, FRANCE
Jean-Pierre ABOULKER, MD study chair
INSERM SC-10, VILLEJUIF, FRANCE
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DNA vaccine pCMVS2.S in people with Chronic Hepatitis B, 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 10 inclusion and 14 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: finished, as of the sponsor's last update on 2 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Primary endpoint is virologic failure defined by 1) reactivation after analogs' treatment interruption, 2) virologic breakthrough during treatment with analogs, 3) the impossibility for the patients to interrupt treatment at week 48 (time frame: at week 72). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00536627, which also lists 4 linked publications.
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 2 Apr 2026.