Safety and Immunogenicity Study of tgAAC09, a Gag-PR-RT AAV HIV Vaccine

Study Overview
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Brief Summary
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The purpose of this study is to determine safety and immunogenicity (ability to induce an immune response) of a novel HIV vaccine based on adeno-associated virus (AAV)

Detailed Description
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The need for a vaccine to prevent AIDS and interrupt transmission of HIV is indisputable. To be effective, an HIV vaccine will have to induce cellular and humoral immune responses that are durable and potent. Intra-muscular delivery of HIV genes enclosed within recombinant adeno-associated virus (rAAV) protein capsid has been shown to be a potent inducer of both antibodies and T-cell responses in animal studies. tgAAC09, consisting of single-stranded DNA from Clade C HIV-1 genes for the gag, protease and part of the reverse transcriptase proteins enclosed within a rAAV serotype 2 protein capsid, was developed as one component of a multi-component HIV vaccine. The purpose of this study is to evaluate the safety and immunogenicity of tgAAC09 in healthy, HIV-seronegative volunteers.

Official Title
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A Phase 1 Randomized, Placebo-controlled, Double-blind Dose-escalation Trial to Evaluate the Safety and Immunogenicity of tgAAC09, a Gag-PR-RT AAV HIV Vaccine

Conditions
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HIV Infection

Intervention / Treatment
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* Biological: tgAAC09


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females Age at least 18 years on the day of screening and no greater than 50 years on the day of vaccination Available for follow-up for the planned duration of the study (screening plus 12 months) Able to give written informed consent; No reported high-risk behavior for HIV (Appendix C), willing to undergo HIV testing and receive results; If sexually active, willing to use or have partner use condoms from screening until at least 4 months after the vaccination. Additional means of contraception are permitted and encouraged. Exclusion Criteria: Clinically relevant abnormality on history or examination including history of immunodeficiency or use of immunosuppressive medication in last 6 months; A chronic medical condition or concurrent condition, which, in the opinion of the investigator, would make the volunteer unsuitable for the study. Any of the following abnormal laboratory parameters that are mild and judged to be clinically significant by the principal investigator or designee, or moderate, severe, or very severe: hematology (hemoglobin, absolute neutrophil count [ANC] absolute lymphocyte count [ALC], absolute CD4 count, platelets); urinalysis, clinical chemistry (total bilirubin, creatinine, AST, ALT). Refer to Appendix D for the grading of these laboratory parameters. If female, pregnant or planning a pregnancy within 4 months after receiving the vaccine, or lactating; Receipt of live attenuated vaccine within 60 days or other vaccine within 14 days of vaccination; Receipt of other experimental HIV vaccine at any time; Receipt of blood transfusion or blood products within 6 months of vaccination; Participation in another clinical trial of an investigational product currently or within 12 weeks of vaccination, or expected during participation in this study; History of severe local or systemic reaction to vaccination or history of allergic reactions to vaccines; Confirmed infection with HIV-1 or HIV-2; Positive for hepatitis B (surface antigen), hepatitis C antibodies, or active syphilis (confirmed by treponemal test such as TPHA in addition to non-treponemal test such as RPR) or active tuberculosis. Unlikely to comply with protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1 AAV-2 HIV Vaccine<br>64 volunteers receiving AAV-2 HIV vaccine tgAAC09 at 3 dosage levels, dose escalation and dose optimization | Biological: tgAAC09<br>* one or 2 doses of AAV-2 HIV vaccine (tgAAC09) at 3 dosage levels, dose escalation and dose optimization<br>* Other names: AAV-2 HIV Vaccine;|
| Placebo Comparator: 2<br>16 volunteers receiving formulation buffer consisting of a buffered salt solution with potassium phosphate, calcium chloride, magnesium chloride, and HEPES | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of one or two doses of tgAAC09 | Safety of one or two doses of tgAAC09 at 3 dosage levels in a dose-escalating an ddose-optimization study | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity |  | up to 6 months post 2nd injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV vaccine, Adeno-associated virus vactored vaccine, HIV-1 subtype C, Safety, Immunogenicity, Biodistribution, HIV prevention