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

February 27, 2014 updated by: Gitte Kronborg

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 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.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark, DK-2650
        • Department Infectious Diseases, Hvidovre university hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Numbers of Treatment Related Side Effects (DLT = Reaction 3 or More)
Time Frame: up to 6 months after end of treatment
the numbers of treatment related side effects (DLT = reaction 3 or more) are registered for participants
up to 6 months after end of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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

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.
10-14 days or 3 months or 6 months after last immunisation
Numbers of Participants With Lowering of HIV RNA Viral-load
Time Frame: up to 6 months after treatment stop

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gitte Kronborg

Collaborators

Rigshospitalet, Denmark
Hvidovre University Hospital
Statens Serum Institut
Ministry of the Interior and Health, Denmark

Investigators

  • Principal Investigator: Gitte Kronborg, MD, Hvidovre University Hospital
  • Study Director: Anders Fomsgaard, MD, Statens Serum Institut
  • Study Chair: Jan Gerstoft, MD, University Hospital Copenhagen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (ACTUAL)

March 1, 2012

Study Completion (ACTUAL)

March 1, 2012

Study Registration Dates

First Submitted

November 6, 2009

First Submitted That Met QC Criteria

November 6, 2009

First Posted (ESTIMATE)

November 9, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

March 27, 2014

Last Update Submitted That Met QC Criteria

February 27, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EudraCT 2008-002980-15
  • 2008-002980-15 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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