Study to Compare the Immunogenicity and Safety of Two HIV Preventive Vaccinations in Healthy Volunteers

Study Overview
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Brief Summary
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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.

Detailed Description
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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: 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; 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

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: DNA-C
* Biological: NYVAC-C


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AIDS Vaccines, Vaccines, DNA, HIV Preventive Vaccine, HIV Seronegativity