Chronic Hepatitis BPhase 1RBM99026NCT00988767
Safety and Immunogenicity of a Naked DNA-based Vaccine Therapy in Patients With Chronic Hepatitis B
A Phase 1 study testing DNA vaccine in people with Chronic Hepatitis B, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
Trial summary
The purpose of this study was to investigate whether HBV-DNA vaccination is safe and could restore immune responses in patients with chronic hepatitis B non responder to available therapies. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- DNA vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteFrance
- Study dates
- Feb 2001to Oct 2004
- Phase
- Phase 1
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- chronic HBV carriers
- biopsy proven chronic hepatitis
- active HBV replication for > 6 months
- non responding to Interferon-alpha or lamivudine treatment
Who cannot join
- co-infection with HIV, HCV, delta hepatitis virus
- alcohol consumption> 40g/day
- decompensated liver disease
- HLA DR2
Trial locations and contacts
1 site in 1 country.
France1 site
Service d'Hepatologie, Hopital Necker Enfants Malades
Paris, 75015
About this study
Official title: Specific Vaccine Therapy in Chronic Hepatitis B Using a Naked DNA: Phase I Study Using a GMO
The purpose of this study was to investigate whether HBV-DNA vaccination is safe and could restore immune responses in patients with chronic hepatitis B non responder to available therapies.
Read the detailed description
- Despite the availability of effective hepatitis B vaccines for many years, over 370 million people remain persistently infected with hepatitis B virus (HBV). Persistent infection is associated with chronic liver disease that can lead to the development of cirrhosis and hepatocellular carcinoma in some patients. Viral persistence is thought to be related to poor HBV-specific immune responses.
- Interferon (IFN)-alpha treatment significantly decreases HBV replication in only one third of patients with hepatitis B e antigen (HBeAg)-positive chronic active hepatitis B. Nucleoside analogues, such as lamivudine and adefovir dipivoxil, inhibit HBV replication and improve histological signs of liver disease,but their use is limited by the risk of relapse after treatment discontinuation and the emergence of drug-resistant viral variants.
- Patients with acute self-limited hepatitis B display detectable polyclonal and multispecific cytotoxic T lymphocyte and T helper (Th) responses to viral antigens,whereas these responses are weak or absent in chronic HBV carriers.
- Increasing the strength of HBV-specific T-cell responses to the levels found in patients recovering from infection is therefore a goal in the treatment of patients with chronic hepatitis.
- Immunization with a nucleic acid vaccine (DNA vaccine) usually elicits antibody responses and T lymphocytes with a Th1 cytokine profile. In animal models of chronic hepatitis B infection, including nonhuman primates, intramuscular injection of a plasmid encoding HBV envelope proteins induces rapid, strong, and sustained humoral and cell-mediated immune responses. Clinical trials of DNA vaccines for hepatitis B conducted in healthy adult volunteers using a plasmid encoding hepatitis B surface antigen and the gene gun as a delivery system showed good tolerance.
- We carried out a phase I trial of a HBV DNA vaccine in patients with chronic active viral hepatitis, aiming to restore HBV-specific immune responses and to assess safety regarding liver disease.
- Conditions
- Chronic Hepatitis B
- Being tested
- DNA vaccine
- Keywords
- Hepatitis B, DNA vaccine, immunotherapy
- Medical subject headings
- Hepatitis B, Chronic, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNA vaccineBiological
Also called pCMV-S2.S DNA
patients received 1ml of DNA vaccine (1mg/ml) at Months 0,2,4,10
| Study group | Role | What they receive |
|---|---|---|
| intramuscular injections | Experimental | Patients received 4 injections of DNA vaccine at M0, M2, M4 and M10 Receives: Biological: DNA vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability (local and general) of the DNA vaccine injections
Measured: every Months from month 0 to month 12 and then M15, M18, M21 and M22
Secondary outcomes (1)
Immunological responses
Measured: before DNA injection (M0), after DNA injection and during follow-up (M1, M3, M5, M10, M11, M15)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2009 (estimated)
- Study startFeb 2001
- Primary completionNov 2003
- Study completionOct 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Helene FONTAINE, MD, Principal investigator, Assistance Publique des Hopitaux de paris, AP-HP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00988767
- Sponsor's protocol ID
- INSERM RBM99.026
- Acronym
- RBM99026
- Status last verified
- Oct 2009
- First submitted
- 1 Oct 2009
- Last updated
- 26 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mancini-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 15382173Mancini-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 16310901Scott-Algara D, Mancini-Bourgine M, Fontaine H, Pol S, Michel ML. Changes to the natural killer cell repertoire after therapeutic hepatitis B DNA vaccination. PLoS One. 2010 Jan 18;5(1):e8761. doi: 10.1371/journal.pone.0008761.
PubMed 20090916
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Specific Vaccine Therapy in Chronic Hepatitis B Using a Naked DNA: Phase I Study Using a GMO
- ClinicalTrials.gov ID
- NCT00988767
- Acronym / sponsor ID
- RBM99026 / INSERM RBM99.026
- Conditions
- Chronic Hepatitis B
- Keywords
- Hepatitis B, DNA vaccine, immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Study start
- Feb 2001
- Primary completion
- Nov 2003 (actual)
- Study completion
- Oct 2004 (actual)
- First posted
- 2 Oct 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.
The purpose of this study was to investigate whether HBV-DNA vaccination is safe and could restore immune responses in patients with chronic hepatitis B non responder to available therapies.
Detailed description
- Despite the availability of effective hepatitis B vaccines for many years, over 370 million people remain persistently infected with hepatitis B virus (HBV). Persistent infection is associated with chronic liver disease that can lead to the development of cirrhosis and hepatocellular carcinoma in some patients. Viral persistence is thought to be related to poor HBV-specific immune responses.
- Interferon (IFN)-alpha treatment significantly decreases HBV replication in only one third of patients with hepatitis B e antigen (HBeAg)-positive chronic active hepatitis B. Nucleoside analogues, such as lamivudine and adefovir dipivoxil, inhibit HBV replication and improve histological signs of liver disease,but their use is limited by the risk of relapse after treatment discontinuation and the emergence of drug-resistant viral variants.
- Patients with acute self-limited hepatitis B display detectable polyclonal and multispecific cytotoxic T lymphocyte and T helper (Th) responses to viral antigens,whereas these responses are weak or absent in chronic HBV carriers.
- Increasing the strength of HBV-specific T-cell responses to the levels found in patients recovering from infection is therefore a goal in the treatment of patients with chronic hepatitis.
- Immunization with a nucleic acid vaccine (DNA vaccine) usually elicits antibody responses and T lymphocytes with a Th1 cytokine profile. In animal models of chronic hepatitis B infection, including nonhuman primates, intramuscular injection of a plasmid encoding HBV envelope proteins induces rapid, strong, and sustained humoral and cell-mediated immune responses. Clinical trials of DNA vaccines for hepatitis B conducted in healthy adult volunteers using a plasmid encoding hepatitis B surface antigen and the gene gun as a delivery system showed good tolerance.
- We carried out a phase I trial of a HBV DNA vaccine in patients with chronic active viral hepatitis, aiming to restore HBV-specific immune responses and to assess safety regarding liver disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| intramuscular injections | Experimental | Biological: DNA vaccinePatients received 4 injections of DNA vaccine at M0, M2, M4 and M10 |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- chronic HBV carriers
- biopsy proven chronic hepatitis
- active HBV replication for > 6 months
- non responding to Interferon-alpha or lamivudine treatment
Key exclusion criteria (4 listed)
- co-infection with HIV, HCV, delta hepatitis virus
- alcohol consumption> 40g/day
- decompensated liver disease
- HLA DR2
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 vaccineAlso: pCMV-S2.S DNApatients received 1ml of DNA vaccine (1mg/ml) at Months 0,2,4,10 | Biological | intramuscular injections |
Primary outcome
Safety and tolerability (local and general) of the DNA vaccine injections
Time frame: every Months from month 0 to month 12 and then M15, M18, M21 and M22
1 secondary outcome
Immunological responses
Time frame: before DNA injection (M0), after DNA injection and during follow-up (M1, M3, M5, M10, M11, M15)
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 26 Sep 2025.
- 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.
- Results publication: 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.
- Derived from this study: PubMed 20090916Scott-Algara D, Mancini-Bourgine M, Fontaine H, Pol S, Michel ML. Changes to the natural killer cell repertoire after therapeutic hepatitis B DNA vaccination. PLoS One. 2010 Jan 18;5(1):e8761. doi: 10.1371/journal.pone.0008761.
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.
Helene FONTAINE, MD principal investigator
Assistance Publique des Hopitaux de paris, AP-HP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DNA vaccine in people with Chronic Hepatitis B, run by Institut National de la Santé Et de la Recherche Médicale, France 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 4 inclusion and 4 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 26 Sep 2025. 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 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.
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?
Safety and tolerability (local and general) of the DNA vaccine injections (time frame: every Months from month 0 to month 12 and then M15, M18, M21 and M22). 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 NCT00988767, which also lists 3 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 26 Sep 2025.