Study to Compare the Immunogenicity and Safety of Two HIV Preventive Vaccinations in Healthy Volunteers (EV03/ANRSVAC20)

This study has been completed.
Sponsor:
Collaborator:
EuroVacc Foundation
Information provided by:
French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:
NCT00490074
First received: June 21, 2007
Last updated: November 25, 2009
Last verified: November 2009

June 21, 2007
November 25, 2009
July 2007
December 2008   (final data collection date for primary outcome measure)
  • Immunogenicity parameter: presence of CD8/CD4+ T cell responses defined according to internationally agreed criteria for evaluation of IFNgamma ELISPOT assays, in response to env plus at least one of the gag, pol, nef peptide pools [ Time Frame: week 26 and week 28 ] [ Designated as safety issue: No ]
  • Safety parameter: grade 3 or above local adverse event, grade 3 or above systemic adverse event, grade 3 or above other clinical or laboratory adverse event,any event attributable to vaccine leading to discontinuation of the immunisation regimen. [ Time Frame: within 72 weeks ] [ Designated as safety issue: No ]
  • Immunogenicity parameter: presence of CD8/CD4+ T cell responses defined according to internationally agreed criteria for evaluation of IFNgamma ELISPOT assays, in response to env plus at least one of the gag, pol, nef peptide pools [ Time Frame: week 26 and week 28 ]
  • Safety parameter: grade 3 or above local adverse event, grade 3 or above systemic adverse event, grade 3 or above other clinical or laboratory adverse event,any event attributable to vaccine leading to discontinuation of the immunisation regimen. [ Time Frame: within 72 weeks ]
Complete list of historical versions of study NCT00490074 on ClinicalTrials.gov Archive Site
  • Cellular responses: CD8/CD4+ T cell mean IFNgamma Spot Forming Units (SFU) per million cells across the peptide pools [ Time Frame: at weeks 26 and 28 ] [ Designated as safety issue: No ]
  • Cellular responses: CD8/CD4+ T cell mean Spot Forming Units (SFU) per million cells across the peptide pools [ Time Frame: at any week following the first immunisation including weeks 48 and 72 ] [ Designated as safety issue: No ]
  • Cellular responses: mean proportion of CD4/CD8+ T cells producing IL-2 and/or IFNgamma following ex-vivo stimulation with HIV-1 peptide pools [ Time Frame: at weeks 26 and 28, 48 and 72 ] [ Designated as safety issue: No ]
  • Cellular responses: number of different epitopes that can be characterised [ Time Frame: to be determined at a later stage ] [ Designated as safety issue: No ]
  • Antibody responses [ Time Frame: to be determined at a later stage ] [ Designated as safety issue: No ]
  • All grade 1 and 2 adverse events [ Time Frame: within 72 weeks ] [ Designated as safety issue: No ]
  • All events including those considered unrelated [ Time Frame: within the 72 weeks ] [ Designated as safety issue: No ]
  • Cellular responses: CD8/CD4+ T cell mean IFNgamma Spot Forming Units (SFU) per million cells across the peptide pools [ Time Frame: at weeks 26 and 28 ]
  • Cellular responses: CD8/CD4+ T cell mean Spot Forming Units (SFU) per million cells across the peptide pools [ Time Frame: at any week following the first immunisation including weeks 48 and 72 ]
  • Cellular responses: mean proportion of CD4/CD8+ T cells producing IL-2 and/or IFNgamma following ex-vivo stimulation with HIV-1 peptide pools [ Time Frame: at weeks 26 and 28, 48 and 72 ]
  • Cellular responses: number of different epitopes that can be characterised
  • Antibody responses
  • All grade 1 and 2 adverse events [ Time Frame: within 72 weeks ]
  • All events including those considered unrelated [ Time Frame: within the 72 weeks ]
Not Provided
Not Provided
 
Study to Compare the Immunogenicity and Safety of Two HIV Preventive Vaccinations in Healthy Volunteers
A Phase I/II Trial to Compare the Immunogenicity and Safety of 3 DNA C Prime Followed by 1 NYVAC C Boost to 2 DNA C Prime Followed by 2 NYVAC C Boost

The purpose of the trial is to evaluate the effect upon immune system of two regimens of preventive HIV vaccination in healthy adult volunteers. Volunteers will be vaccinated by DNA-C and NYVAC-C vaccines, and the immune changes will be assessed, as well as safety of the vaccines. Volunteers will be followed during 72 weeks.

Methods: randomised phase I/II international trial with a parallel group design, open to participants and investigators but blind to laboratory personnel, in healthy volunteers.

Vaccines strategies: 70 volunteers will receive 3 DNA-C vaccinations and 1 NYVAC-C vaccination; 70 volunteers will receive 2 DNA-C vaccinations and 2 NYVAC-C vaccination.

DNA-C: 2x2ml intra muscular in right and left vastus lateralis; NYVAC-C: 1 ml intramuscular in non-dominant deltoid.

Main outcome:

  1. the presence of CD8/CD4+ T cell responses defined according to internationally agreed criteria for evaluation of IFNgamma ELISPOT assays:

    • in response to env plus at least one of the gag, pol, nef peptide pools,
    • at weeks 26 or 28;
  2. the safety parameters.

Secondary outcomes:

  • cellular responses,
  • antibody responses,
  • all grade 1 and 2 adverse events,
  • all events including those considered unrelated.

Sample size: 140 volunteers

Enrollment period: 9 months

Patient's participation duration: 78 weeks

Study duration: 27 months

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
HIV Infections
  • Biological: DNA-C
    1.0mg per ml of DNA HIV-C vaccine 2x2 ml IM
  • Biological: NYVAC-C
    NYVAC-C 1 ml IM
  • Experimental: 3 DNA-C + 1 NYVAC-C
    Interventions:
    • Biological: DNA-C
    • Biological: NYVAC-C
  • Active Comparator: 2 DNA-C + 2 NYVAC-C
    Interventions:
    • Biological: DNA-C
    • Biological: NYVAC-C
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
147
October 2009
December 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • age between 18 and 55 years on the day of screening
  • available for follow-up for the duration of the study (78 weeks from screening)
  • able to give written informed consent
  • at low risk of HIV and willing to remain so for the duration of the study low risk of HIV infection defined as:

    • no history of injecting drug use in the previous ten years
    • no gonorrhoea or syphilis in the last six months
    • no high risk partner (e.g. injecting drug use, HIV positive partner) either currently or within the past six months
    • no unprotected anal intercourse in the last six months, outside a relationship with a regular partner known to be HIV negative
    • no unprotected vaginal intercourse in the last six months outside a relationship with a regular known/presumed HIV negative partner
  • willing to undergo a HIV test
  • willing to undergo a genital infection screen
  • if heterosexually active female, using an effective method of contraception with partner (combined oral contraceptive pill; injectable contraceptive; IUCD; consistent record with condoms if using these; physiological or anatomical sterility in self or partner) from 14 days prior to the first vaccination until 4 months after the last, and willing to undergo urine pregnancy tests prior to each vaccination
  • if heterosexually active male, using an effective method of contraception with their partner from the first day of vaccination until 4 months after the last vaccination
  • for French volunteers only :

    • subjects registered in French Health ministry computerised file and authorised to participate in a clinical trial
    • subjects covered by Health Insurance
    • subjects included in the ANRS vaccine research network of volunteers

Exclusion Criteria:

  • pregnant or lactating
  • clinically relevant abnormality on history or examination including history of grand-mal epilepsy; severe eczema; allergy to eggs or gentamicin; severe allergic diseases; liver disease with inadequate hepatic function; haematological, metabolic or gastrointestinal disorders; uncontrolled infection; autoimmune disease, immunodeficiency or use of immunosuppressives in preceding 3 months
  • receipt of live attenuated vaccine within 60 days or other vaccine within 14 days of enrolment
  • receipt of blood products or immunoglobin within 4 months of screening
  • participation in another trial of a medicinal product, completed less than 30 days prior to enrolment
  • history of severe local or general reaction to vaccination defined as

    • local: extensive, indurated redness and swelling involving most of the anterolateral thigh or the major circumference of the arm, not resolving within 72 hours
    • general: fever >= 39.5oC within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours
  • HIV 1/2 positive or indeterminate on screening
  • positive for hepatitis B surface antigen, hepatitis C antibody or serology indicating active syphilis requiring treatment
  • positive for DNA/ANA antibodies at titre considered clinically relevant by immunology laboratory
  • grade 1 or above routine laboratory parameters (see section 4.1.4 & appendix 4 for definitions) Note of clarification 18th april 2008: hyperbilirubinemia has to be considered as an exclusion criterion only when confirmed to be conjugated bilirubinemia
  • unlikely to comply with protocol
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
France,   Switzerland
 
NCT00490074
2006-006141-13, EV03/ANRSVAC20
Yes
Agence Nationale de la Recherche sur le Sida et les Hepatites virales (ANRS), French National Agency for Research on AIDS and Viral Hepatitis
French National Agency for Research on AIDS and Viral Hepatitis
EuroVacc Foundation
Principal Investigator: Yves LEVY, MD; PhD Hôpital Henri Mondor-Créteil-France
Principal Investigator: Giuseppe PANTALEO, MD; PhD Hospices CHUV-Lausanne-Switzerland
French National Agency for Research on AIDS and Viral Hepatitis
November 2009

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