Intranasal Modified Vacc-4x Gag Peptides With Endocine as Adjuvant

June 19, 2012 updated by: Oslo University Hospital

Immunotherapy of HIV-infected Patients: A Single-blinded, Randomized, Immunogenicity, Pilot Study of Intranasal Administration of Vacc-4x With Endocine as Adjuvant

HIV-specific cellular immunity is hampered in most HIV-infected individuals. Therapeutic immunization in HIV aims to strengthen the HIV-specific cellular immunity, usually in the absence of replicating HIV with antiretroviral drugs. The aims of this strategy can be to decrease the mass of latently infected CD4+ T cells, better tolerance of drug-free periods, and better select candidates for preventive HIV vaccines.

Vacc-4x is one of the few peptide-based therapeutic vaccines tested, and consists of four, slightly modified HIV Gag p24 consensus peptides. Vacc-4x was first tested by intradermal injections using GM-CSF as adjuvant. A recent multinational placebo-controlled study found improvement of vaccine-specific T cell immunity and decrease in viral loads (presented at the AIDS vaccine 2011 conference, Bangkok).

In this study the investigators hypothesize that the Vacc-4x peptides, deposited on the nasal mucosal surfaces in conjunction with Endocine, a newly developed and documented mucosal adjuvant, will induce T cell responses to HIV and improve HIV-specific immunity both systemically and at mucosal surfaces (oral, rectal, vaginal).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

HIV-specific cellular immunity is hampered in most HIV-infected individuals, partly because the virus infects CD4+ T cells, the key cell subset in all immune responses. CD4 is the primary HIV receptor (CD4), but infection requires a co-receptor (CCR5) which is carried mainly by activated T cells. During primary HIV-infection, two types of CD4+ T cells mainly become infected: (i) Sub-activated T cells of all specificities within the mucosal linings, particularly in the gut; and (ii) HIV-specific T cell clones, that proliferates and are activated as a normal response to HIV infection itself. The HIV-specific immunity therefore becomes severely compromised early in the infection. Patients having better T cells specific to parts of the HIV Gag matrix protein usually progress slower towards AIDS than patients with poor T cell responsitivity towards Gag.

Therapeutic immunization in HIV aims to strengthen the HIV-specific cellular immunity, usually in the absence of replicating HIV with antiretroviral drugs. The aims of this strategy can be to decrease the mass of latently infected CD4+ T cells, better tolerance of drug-free periods, and better select candidates for preventive HIV vaccines. The latter point may be important since clinical trials with preventive vaccine candidates may challenge our ethical standards: Such trials must be very large and conducted in poor areas with high prevalence of HIV, in order to have as many (placebo) or few (vaccine candidate) new HIV infections as fast as possible. Preventive vaccine trials might therefore compete with introduction of "western" access to HIV drugs.

Vacc-4x is one of the few peptide-based therapeutic vaccines tested, and consists of four, slightly modified HIV Gag p24 consensus peptides. Vacc-4x was first tested by intradermal injections using GM-CSF as adjuvant. In a dose study at our Hospital, the investigators found induction of robust cellular immune responses both in vitro and in vivo by skin testing, indications of improved viral control, long-lasting immunity and lack of mutational changes in the HIV strains within the study cohort. A recently completed multinational placebo-controlled study found improvement of viral loads (presented at the AIDS vaccine 2011 conference, Bangkok).

In this study the investigators hypothesize that the Vacc-4x peptides, deposited on the nasal mucosal surfaces in conjunction with Endocine, a newly developed and documented mucosal adjuvant, will induce T cell responses to HIV and improve HIV-specific immunity both systemically and at mucosal surfaces (oral, rectal, vaginal). This route of application may even simplify mass vaccination. The study is primarily a dose-study focused on adverse events, which have been negligible when Vacc-4x was given parenterally, as well as induction of systemic and mucosal immunity.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 2
  • 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

  • Norway
      • Oslo, Norway, NO-0450
        • Department of Infectious Diseases, Oslo 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 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age above 18 years, both genders.
  • HIV positive at least one year.
  • Clinically stable on ART for the last 6 months (changes in therapy is allowed as long as the viral load is stable).
  • Documented viral load (HIV-1 RNA) less than 50 copies/mL for the last six months.
  • Documented stable CD4 cell count ≥ 400x106/L.
  • Nadir (lowest ever) CD4 cell count ≥ 200x106/L.
  • Signed informed consent.

Exclusion Criteria:

  • Reported pre-study AIDS-defining illness within the previous year.
  • Malignant disease.
  • On chronic treatment with immunosuppressive therapy.
  • Unacceptable values of the hematologic and clinical chemistry parameters, as judged by the Principle Investigator (or designee), including creatinine values >1.5x upper limit of normal (ULN), and AST (SGOT), ALT (SGPT) and alkaline phosphatase values >2.5x ULN.
  • Concurrent chronic active infection such as chronic viral hepatitis B or C or active tuberculosis.
  • Pregnant or breastfeeding women.
  • Women of childbearing potential not using reliable and adequate contraceptive methods (defined as: use of oral, implanted, injectable, mechanical or barrier products for the prevention of pregnancy; practicing abstinence; sterile) during the study, or sexually active male patients with partners of childbearing potential unwilling to practice effective contraception during the study.
  • Current participation in other clinical therapeutic studies.
  • Incapability of compliance to the treatment protocol, in the opinion of the Investigator.

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: FACTORIAL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Vacc-4x low dose
80 µg Vacc-4x (20 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity
Biological: Vacc-4x low dose
80 µg Vacc-4x (20 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks
Other Names:
  • Vacc-4x
  • Endocine
EXPERIMENTAL: Vacc-4x medium dose
400 µg Vacc-4x (100 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity
Biological: Vacc-4x medium dose
400 µg Vacc-4x (100 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks
Other Names:
  • Vacc-4x
  • Endocine
EXPERIMENTAL: Vacc-4x high dose
1200 µg Vacc-4x (300 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity
Biological: Vacc-4x high dose
1200 µg Vacc-4x (300 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks
Other Names:
  • Vacc-4x
  • Endocine
PLACEBO_COMPARATOR: Zero dose
Adjuvant only, i.e. 300 µl Endocine divided into two administrations, one for each nose cavity
Biological: Zero dose
300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks
Other Names:
  • Endocine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the safety of intranasal administration of Vacc-4x with Endocine as adjuvant at three different dose levels
Time Frame: 2 months after completion of last patient.
Record adverse events including severe adverse events according to GCP
2 months after completion of last patient.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate cellular immune response to Vacc-4x in vivo by Vacc-4x DTH skin test
Time Frame: Up to 2 months after completion of last patient
Record intradermal Vacc-4x-associated delayed-type hypersensitivity test (DTH) in vivo by measuring skin induration (area) 2 days after injecion qt end of study week 8, in comparison with 38 historical unvaccinated HIV seropositive controls
Up to 2 months after completion of last patient
Evaluate cellular immune response to Vacc-4x in vitro
Time Frame: Up to 6 months after completion of last patient
Measure changes in Vacc-4x-specific T cell proliferation and activation compared with baseline values for each individual participant, i.e. before vaccination
Up to 6 months after completion of last patient
Evaluate the effect on CD4+ T cell counts and viral load (HIV-1 RNA) in peripheral blood
Time Frame: Up to 2 months after completion of last patient
Measure individual changes in CD4 counts and viral loads at baseline
Up to 2 months after completion of last patient

Collaborators and Investigators

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

Sponsor

Oslo University Hospital

Collaborators

Eurocine Vaccines AB
Bionor Immuno AS

Investigators

  • Principal Investigator: Dag Kvale, Professor/MD, Oslo University Hospital

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

Helpful Links

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

November 1, 2011

Primary Completion (ACTUAL)

March 1, 2012

Study Completion (ACTUAL)

March 1, 2012

Study Registration Dates

First Submitted

November 1, 2011

First Submitted That Met QC Criteria

November 14, 2011

First Posted (ESTIMATE)

November 17, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

June 20, 2012

Last Update Submitted That Met QC Criteria

June 19, 2012

Last Verified

June 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTN-Vacc-4x/L3-2011/1

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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