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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Biological: DNA-C; Biological: NYVAC-C

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Créteil, France, 94010
    • Hôpital Henri Mondor
• Switzerland
  • Lausanne, Switzerland, 1011
    • Centre hospitalier universitaire vaudois CHUV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3 DNA-C + 1 NYVAC-C	Biological: DNA-C; 1.0mg per ml of DNA HIV-C vaccine 2x2 ml IM; Biological: NYVAC-C; NYVAC-C 1 ml IM
Active Comparator: 2 DNA-C + 2 NYVAC-C	Biological: DNA-C; 1.0mg per ml of DNA HIV-C vaccine 2x2 ml IM; Biological: NYVAC-C; NYVAC-C 1 ml IM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	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.	within 72 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Cellular responses: CD8/CD4+ T cell mean IFNgamma Spot Forming Units (SFU) per million cells across the peptide pools	at weeks 26 and 28
Cellular responses: CD8/CD4+ T cell mean Spot Forming Units (SFU) per million cells across the peptide pools	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	at weeks 26 and 28, 48 and 72
Cellular responses: number of different epitopes that can be characterised	to be determined at a later stage
Antibody responses	to be determined at a later stage
All grade 1 and 2 adverse events	within 72 weeks
All events including those considered unrelated	within the 72 weeks

Collaborators and Investigators

• Sponsor: French National Agency for Research on AIDS and Viral Hepatitis
• Collaborators: EuroVacc Foundation
• Investigators: Principal Investigator: Yves LEVY, MD; PhD, Hôpital Henri Mondor-Créteil-France; Principal Investigator: Giuseppe PANTALEO, MD; PhD, Hospices CHUV-Lausanne-Switzerland

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: June 21, 2007
• First Submitted That Met QC Criteria: June 21, 2007
• First Posted (Estimate): June 22, 2007

Study Record Updates

• Last Update Posted (Estimate): November 26, 2009
• Last Update Submitted That Met QC Criteria: November 25, 2009
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: HIV Seronegativity; AIDS Vaccines; HIV Preventive Vaccine; Vaccines, DNA
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: 2006-006141-13; EV03/ANRSVAC20