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| ID | Type | Description | Link |
|---|---|---|---|
| 2008-002980-15 | EudraCT Number |
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| Name | Class |
|---|---|
| Statens Serum Institut | OTHER |
| Rigshospitalet, Denmark | OTHER |
| Hvidovre University Hospital | OTHER |
| Ministry of the Interior and Health, Denmark |
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Treatment: Immunization with a peptide-mix of 17 Clusters of Differentiation number 8 (CD8) T cell minimal epitopes and 3 Clusters of Differentiation number 4 (CD4) T cell epitopes and a new adjuvant (CAF01). The vaccine should induce cellular immunity against human immuno-deficiency virus type-1 (HIV-1).
Target group: Untreated healthy individuals with chronic HIV-1 infection who are 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 T cell immunity, lowering of HIV-1 ribonucleic acid (RNA) viral load in plasma, 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 cytotoxic T lymphocyte (CTL) immunity to selected relatively immune silent (subdominant) but conserved CTL 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.
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 acquired immuno deficiency syndrome (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 major histocompatibility complex class 1 (MHC-I) restricted CD8-t-cell epitopes and 3 MHC class-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 Cationic Adjuvant Formulation number 1 (CAF01) composed of dimethyl-deoctadecylammonium (DDA) and trehalose-dibehenate (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 Dendritic Cells (DC) 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Saline | Placebo Comparator | 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. | |
| AFO-18 vaccine | Active Comparator | the intervention is injection of the experimental therapeutic peptide vaccine (AFO-18) consisting of 18 peptides in CAF01 adjuvant intra muscularly (i.m.) week 0, 2, 4, 8 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| peptide vaccine (AFO-18) | Biological | 18 Peptides (250 ug of each peptide) in Adjuvant CAF01 (= 625/125 ug DDA/TDB), i.m. injection week 0, 2, 4, 8. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Numbers of Treatment Related Side Effects (DLT = Reaction 3 or More) | the numbers of treatment related side effects (DLT = reaction 3 or more) are registered for participants | up to 6 months after end of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With New T Cell Response to the Vaccine Target Epitopes | Number of Participants with New T Cell Response to the Vaccine Target Epitopes as Measured by Intracellular Cytokine Stain Flowcytometry (IC-FACS) and/or IFNg-ELISPOT Analysis. Criteria's for meeting anticipated secondary end-point was that >50% of vaccinees reacted with new Clusters of differentiation 8 (CD8) T-cell and/or Clusters of differentiation 4 (CD4) T-cell response to al least one of the vaccine target epitopes as measured by IC-Facs and/or interferon-gamma (IFNg) - Enzyme-Linked ImmunoSpot (ELISPOT) assays. |
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Inclusion Criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gitte Kronborg, MD | Hvidovre University Hospital | Principal Investigator |
| Anders Fomsgaard, MD | Statens Serum Institut | Study Director |
| Jan Gerstoft, MD | University of Copenhagen | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department Infectious Diseases, Hvidovre university hospital | Copenhagen | DK-2650 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19528789 | Background | Kloverpris H, Karlsson I, Bonde J, Thorn M, Vinner L, Pedersen AE, Hentze JL, Andresen BS, Svane IM, Gerstoft J, Kronborg G, Fomsgaard A. Induction of novel CD8+ T-cell responses during chronic untreated HIV-1 infection by immunization with subdominant cytotoxic T-lymphocyte epitopes. AIDS. 2009 Jul 17;23(11):1329-40. doi: 10.1097/QAD.0b013e32832d9b00. | |
| 23314272 |
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20 participant numbers were randomised to vaccine or placebo but at the deadline for expiring of the vaccine only 11 participants were enrolled but all 11 completed the study
Participants were recruited at the infectious disease department at the University hospitals
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | AFO-18 Vaccinated | Patients receiving the experimental therapeutic vaccine |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | AFO-18 Vaccinated | Patients receiving the experimental therapeutic vaccine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Numbers of Treatment Related Side Effects (DLT = Reaction 3 or More) | the numbers of treatment related side effects (DLT = reaction 3 or more) are registered for participants | Interview, questionaire, objective examination by medical doctor, blood testing for hematology, clinical chemistry, CD4 counts, HIV-1 viral load | Posted | Number | side effects | up to 6 months after end of treatment |
|
6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vaccinee | participants receiving the vaccine called "AFO-18" |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Anders Fomsgaard | Statens Serum Institut | +45-32683460 | afo@ssi.dk |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| D000096202 | Protein Subunit Vaccines |
| D010455 | Peptides |
| ID | Term |
|---|---|
| D022282 | Vaccines, Acellular |
| D022223 | Vaccines, Subunit |
| D014612 | Vaccines |
| D001688 | Biological Products |
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| OTHER_GOV |
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|
| 10-14 days or 3 months or 6 months after last immunisation |
| Numbers of Participants With Lowering of HIV RNA Viral-load | HIV-1 RNA Viral load was measured by Quantitative-PCR in plasma as numbers of virus RNA copies/mm^3 relative to baseline viral-load for each participant. The numbers of participant with lowering of HIV RNA plasma Viral-load is counted at base-line and at 6 months (end of study) and provided in the table (analysis population description) and the number of participants that showed lowering of viral-load was counted. Criteria for this anticipated end-point was a significant lowering of HIV RNA viral-load in >50% of responders (defined as participants with new T-cell responses). | up to 6 months after treatment stop |
| Karlsson I, Brandt L, Vinner L, Kromann I, Andreasen LV, Andersen P, Gerstoft J, Kronborg G, Fomsgaard A. Adjuvanted HLA-supertype restricted subdominant peptides induce new T-cell immunity during untreated HIV-1-infection. Clin Immunol. 2013 Feb;146(2):120-30. doi: 10.1016/j.clim.2012.12.005. Epub 2012 Dec 21. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Clusters of Differentiation 4 (CD4) T-cells >400 cells/mm^3 | Number | participants |
|
| Absence of T cell reaction to all vaccine peptides | Number | participants |
|
| Viral load >10^3/mm^3 plasma | Numbers of participants with Viral Load in plasma above 1000 copies per ml | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Number of Participants With New T Cell Response to the Vaccine Target Epitopes | Number of Participants with New T Cell Response to the Vaccine Target Epitopes as Measured by Intracellular Cytokine Stain Flowcytometry (IC-FACS) and/or IFNg-ELISPOT Analysis. Criteria's for meeting anticipated secondary end-point was that >50% of vaccinees reacted with new Clusters of differentiation 8 (CD8) T-cell and/or Clusters of differentiation 4 (CD4) T-cell response to al least one of the vaccine target epitopes as measured by IC-Facs and/or interferon-gamma (IFNg) - Enzyme-Linked ImmunoSpot (ELISPOT) assays. | Peripheral Blood Mononuclear Cells (PBMC) from blood was measured in IFNg-ELISPOT and/or Intracellular Cytokines (ICS) Flowcytometry for T cell responses. All 10 vaccinee developed a new T cell immune response to at least one vaccine epitope. The saline placebo did not develop any new t cell responses. | Posted | Number | participants | 10-14 days or 3 months or 6 months after last immunisation |
|
|
|
| Secondary | Numbers of Participants With Lowering of HIV RNA Viral-load | HIV-1 RNA Viral load was measured by Quantitative-PCR in plasma as numbers of virus RNA copies/mm^3 relative to baseline viral-load for each participant. The numbers of participant with lowering of HIV RNA plasma Viral-load is counted at base-line and at 6 months (end of study) and provided in the table (analysis population description) and the number of participants that showed lowering of viral-load was counted. Criteria for this anticipated end-point was a significant lowering of HIV RNA viral-load in >50% of responders (defined as participants with new T-cell responses). | the numbers of participants that showed changes (lowering of) in Viral load (measured as HIV-1 RNA copies/mm^3 plasma in commercial quantitative PCR) at end of study (6 months after vaccination) relative to base-line viral-load was counted at 6 month after vaccination (end of study) | Posted | Number | participants | up to 6 months after treatment stop |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | Placebo | Participants receiving placebo (saline) | 0 | 1 | 0 | 1 |
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| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D045424 |
| Complex Mixtures |
| D000602 | Amino Acids, Peptides, and Proteins |