Immunization With HIV-1 Peptides in Adjuvant for Treatment of Patients With Chronic HIV-infection
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Purpose
Treatment: Immunization with peptide-mix of 17 CD8 T cell minimal epitopes and 3 CD4 T cell epitopes and a new adjuvant (CAF01). The vaccine should induce cellular immunity against HIV-1.
Target group: Untreated healthy individuals with chronic HIV-1 infection not in antiretroviral treatment.
Purpose: The primary purpose is to evaluate tolerability and safety of the vaccine.
The secondary purpose is to evaluate the clinical effect of the vaccination treatment as measured by induction of new immunity, lowering of viral load, induction of escape mutations in the virus and improvement in the patient CD4 lymphocyte blood counts.
Design: The experiment is designed as a single-blinded, placebo-controlled phase 1 clinical trial in HIV-1 infected individuals in Denmark.
Numbers of individuals: 20 fully evaluable HIV-1-infected patients should enter the study (15 vaccine treated and 5 placebo(saline) treated controls).
The hypothesis is that a redirection of CTL immunity to selected relatively immune silent (subdominant) but conserved targets on multiple sites in HIV-1 could provide a better immune control of the virus replication. This could result in lowering of viral load thereby prolonging the time to antiretroviral therapy.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV Infections |
Biological: peptide vaccine (AFO-18) |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment |
| Official Title: | Immunization With HIV-1 Peptides in Adjuvant for Treatment of Patients With |
- Primary end point: Maximum of 3 patients out of the 15 vaccinated showing treatment related side effects (DLT = reaction 3 or more) related to the treatment. [ Time Frame: up to 6 months after end of treatment ] [ Designated as safety issue: Yes ]
- Induction of T-CD8 cell mediated immunity against one or more of the vaccine epitopes in half or more of the patients receiving the vaccine. [ Time Frame: 10-14 days after last immunisation ] [ Designated as safety issue: No ]
- Significant lowering of RNA or DNA viral load in at last half of the patients who responded with a new immun response on epitopes present in their virus 3 and/or 6 months after treatment stop and/or appearance of escape mutations in their virus RNA [ Time Frame: up to 6 months after treatment stop ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 20 |
| Study Start Date: | September 2009 |
| Estimated Study Completion Date: | December 2010 |
| Estimated Primary Completion Date: | July 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Placebo Comparator: Saline
Sterile saline for injection is used as placebo arm. It is administered i.m. in the same way as for the active vaccine, week 0, 2, 4, 8.
|
Biological: peptide vaccine (AFO-18)
18 Peptides (250 ug of each peptide) in Adjuvant CAF01 (= 625/125 ug DDA/TDB), i.m. injection week 0, 2, 4, 8.
Other Names:
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Active Comparator: AFO-18 vaccinated
Patients receiving the experimental therapeutic vaccine
|
Biological: peptide vaccine (AFO-18)
18 Peptides (250 ug of each peptide) in Adjuvant CAF01 (= 625/125 ug DDA/TDB), i.m. injection week 0, 2, 4, 8.
Other Names:
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Detailed Description:
The HIV-1 vaccine in this trial is designed to prevent disease in healthy already HIV-1 infected individuals not in anti-retroviral treatment by inducing a strong cellular immune response against several immune subdominant selected target points in the patient's HIV-1 virus. The vaccine treatment is not harmful but could potentially lower viral load and thus delay the time to AIDS disease or to the need of antiviral medicine and thereby limit the spread of HIV-1 in the population.
The patient's cellular immune response can only partly control the HIV-1 infection and eventually leads to a destruction of the immune system, opportunistic infections, and ultimately death. Normally the natural HIV-1 infection does not provide adequate immunity and vaccines must therefore induce a more potent and broader and more rationally directed immunity. Individuals that have this kind of strong immunity have lower viral-load and live longer. The vaccine in this study is designed to develop this kind of potent cellular immunity against HIV-1, so the virus is controlled better by the individual and spread in the population is limited.
This vaccine is designed to match most individual's cellular immune system (HLA tissue types) and several conserved target points in the individual's own HIV-1 virus. On the basis of our previous vaccine trial of HIV vaccination of HIV-infected individuals in Denmark and years of research, we have been able to develop this HIV-1 vaccine. Our vaccine contains 18 peptides (15 MHC-I restricted CD8-t-cell epitopes and 3 MHC II restricted CD4 T-cell epitopes) in a mix and should induce cellular immune responses to several conserved target points identified in HIV-1. Our vaccine is composed of 18 peptides in a lipid based adjuvant (CAF01) composed of DDA and TDB and is deemed safe and the technique is simple and also called 'peptide vaccination'. This and similar techniques have been tried in several studies against virus diseases around the world.
We want to know to which degree it is possible to immunize already HIV¬ 1 infected individuals to prolong the healthy period and prevent disease before initiation of antiviral medicine or other treatments of AIDS. In the present immunization study, healthy HIV-1 infected individuals not in treatment in Denmark will be invited to participate. This vaccine study will examine the immune responses and effects of the vaccine on these healthy HIV-1-infected individuals. The first purpose is first to determine if there are any side-effects of the vaccine. From several trials on animals and humans and in our own recent HIV vaccination trial on HIV-1 infected individuals in Denmark, with very similar vaccine techniques (peptides in autologous DC cells) no serious side-effects has been observed. The second purpose is to examine if the vaccine induces the expected immune responses in HIV-1 infected individuals and how it enforces and supplements the already existing 'own' immune response of the infected individual. Finally, a clinical beneficial effect (on viral load and CD4 counts) of our vaccine will be evaluated.
Eligibility| Ages Eligible for Study: | 18 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- HIV-1 seropositive with measurable viral load >10e3 copies/ml and CD4+ T-cell count >400 CD4+ cells/µl.
- Not in Antiretroviral Therapy (>1 year).
- Male or female with age between 18 and 60 years, where females are not breastfeeding, are not pregnant and use contraception until at least 3 months after end of vaccinations.
- Normal values for the area of liver and kidney enzymes, blood cell count with differential counts (e.g. white blood cells, lymphocytes, platelets/thrombocytes) and Hemoglobin
- Expected to follow the instructions.
- Written informed consent after oral and written information.
Exclusion criteria
- Vaccinated with other experimental vaccines within 3 months before the first vaccination.
- Treated with immune modulating medicine within 3 month before the first immunization.
- Other significant active chronic infectious diseases likely to influence the HIV-1 infection, like HBV, HCV
- Significant medical disease as judged by the investigators, for example severe asthma/COLD, badly regulated heart disease, insulin-dependent diabetes mellitus.
- Severe allergy or earlier anaphylactic reactions.
- Active autoimmune diseases.
- Simultaneous treatment with other experimental drugs.
- Laboratory parameters outside the 'normal' range for the area and which are considered clinically significant.
- Pregnancy and/or brest feeding
Contacts and Locations| Denmark | |
| Department Infectious Diseases, Hvidovre university hospital | |
| Copenhagen, Denmark, DK-2650 | |
| Principal Investigator: | Gitte Kronborg, MD | Hvidovre University Hospital |
| Study Director: | Anders Fomsgaard, MD | Statens Serum Institut |
| Study Chair: | Jan Gerstoft, MD | University Hospital Copenhagen |
More Information
Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Gitte Kronborg, Hvidovre University Hospital |
| ClinicalTrials.gov Identifier: | NCT01009762 History of Changes |
| Other Study ID Numbers: | EudraCT 2008-002980-15 |
| Study First Received: | November 6, 2009 |
| Last Updated: | November 12, 2009 |
| Health Authority: | Denmark: Danish Medicines Agency Denmark: Ethics Committee |
Keywords provided by Hvidovre University Hospital:
|
VACCINE THERAPY CELLULAR IMMUNITY IMMUNITY |
Additional relevant MeSH terms:
|
HIV Infections Acquired Immunodeficiency Syndrome Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases |
Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 19, 2013