Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Immunization With HIV-1 Peptides in Adjuvant for Treatment of Patients With Chronic HIV-infection (HIV-VAC)

This study has been completed.
Sponsor:
Collaborators:
Statens Serum Institut
Rigshospitalet, Denmark
Hvidovre University Hospital
Ministry of the Interior and Health, Denmark
Information provided by (Responsible Party):
Gitte Kronborg, Hvidovre University Hospital
ClinicalTrials.gov Identifier:
NCT01009762
First received: November 6, 2009
Last updated: February 27, 2014
Last verified: February 2014

November 6, 2009
February 27, 2014
September 2009
March 2012   (final data collection date for primary outcome measure)
Numbers of Treatment Related Side Effects (DLT = Reaction 3 or More) [ Time Frame: up to 6 months after end of treatment ] [ Designated as safety issue: Yes ]
the numbers of treatment related side effects (DLT = reaction 3 or more) are registered for participants
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 ]
Complete list of historical versions of study NCT01009762 on ClinicalTrials.gov Archive Site
  • Number of Participants With New T Cell Response to the Vaccine Target Epitopes [ Time Frame: 10-14 days or 3 months or 6 months after last immunisation ] [ Designated as safety issue: No ]

    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.

  • Numbers of Participants With Lowering of HIV RNA Viral-load [ Time Frame: up to 6 months after treatment stop ] [ Designated as safety issue: No ]

    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).

  • 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 ]
Not Provided
Not Provided
 
Immunization With HIV-1 Peptides in Adjuvant for Treatment of Patients With Chronic HIV-infection
Immunization With HIV-1 Peptides in Adjuvant for Treatment of Patients With

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
HIV INFECTIONS
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:
  • DDA/TDB
  • peptides
  • 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.
  • Active Comparator: AFO-18 vaccine
    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
    Intervention: Biological: peptide vaccine (AFO-18)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
11
March 2012
March 2012   (final data collection date for primary outcome measure)

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 Hepatitis B Virus (HBV), Hepatitis C Virus (HCV)
  • Significant medical disease as judged by the investigators, for example severe asthma/chronic obstructive lung disease (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
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT01009762
EudraCT 2008-002980-15, 2008-002980-15
Yes
Gitte Kronborg, Hvidovre University Hospital
Gitte Kronborg
  • Statens Serum Institut
  • Rigshospitalet, Denmark
  • Hvidovre University Hospital
  • Ministry of the Interior and Health, Denmark
Principal Investigator: Gitte Kronborg, MD Hvidovre University Hospital
Study Director: Anders Fomsgaard, MD Statens Serum Institut
Study Chair: Jan Gerstoft, MD University Hospital Copenhagen
Hvidovre University Hospital
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP