HVTN Protocol 204 - A Phase II Clinical Trial to Evaluate the Safety and Immunogenicity of a Multiclade HIV-1 DNA Plasmid Vaccine, VRC-HIVDNA016-00-VP, Followed by a Multiclade Recombinant Adenoviral Vector HIV-1 Vaccine Boost, VRCHIVADV014-00-VP, in HIV-1 Uninfected Adult Participants

Study Overview
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Brief Summary
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The purpose of the study is to determine the safety of and immune response to a DNA HIV vaccine followed by an adenoviral vector HIV vaccine in HIV uninfected adults.

Detailed Description
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The worldwide HIV/AIDS epidemic may only be controlled through development of a safe and effective vaccine that will prevent HIV infection. DNA vaccines are inexpensive to construct, readily produced in large quantities, and stable for long periods of time. This study will evaluate the safety and immunogenicity of an experimental multiclade HIV vaccine, VRC-HIVDNA016-00-VP, followed by a similarly structured adenovirus-vectored vaccine boost, VRC-HIVADV014-00-VP, in HIV uninfected adults. The DNA plasmids in both the vaccines code for proteins from HIV subtypes A, B, and C, which together represent 90% of new HIV infections in the world. Participants in this study will be recruited in North America, South America, and Africa. Each volunteer will participate in the study for 36 months. Participants will be randomly assigned to one of two groups. Group 1 participants will receive the DNA HIV vaccine at study entry and at Months 1 and 2. At Month 6, Group 1 participants will receive an injection of the adenoviral vector HIV vaccine. Group 2 participants will receive placebo at study entry and Months 1, 2, and 6. There will be 17 study visits, which will occur at study entry and every 2 weeks thereafter until Day 70; at Month 6 and every 2 weeks thereafter until Day 210; and Months 9.5, 12, 18, 24, 30, and 36. A physical exam, adverse events reporting, HIV and pregnancy prevention counseling, and medication history will occur at each visit. Blood and urine collection will occur at selected visits.

Official Title
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HVTN Protocol 204 - A Phase II Clinical Trial to Evaluate the Safety and Immunogenicity of a Multiclade HIV-1 DNA Plasmid Vaccine, VRC-HIVDNA016-00-VP, Followed by a Multiclade Recombinant Adenoviral Vector HIV-1 Vaccine Boost, VRCHIVADV014-00-VP, in HIV-1 Uninfected Adult Participants

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: VRC-HIVDNA016-00-VP
* Biological: VRC-HIVADV014-00-VP
* Biological: VRC-HIVDNA016-00-VP placebo
* Biological: VRC-HIVADV014-00-VP placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV uninfected Has access to a participating HIV Vaccine Trials Unit (HVTU) and willing to be followed for the duration of the study Willing to receive HIV test results Good general health Willing to use acceptable forms of contraception Completed at least 12 years of schooling (South African participants only) Exclusion Criteria: HIV vaccines in prior HIV vaccine trial Immunosuppressive medications within 168 days prior to first study vaccine administration Blood products within 120 days prior to first study vaccine administration Immunoglobulin within 60 days prior to first study vaccine administration Live attenuated vaccines within 30 days prior to first study vaccine administration Investigational research agents within 30 days prior to first study vaccine administration Subunit or killed vaccines within 14 days prior to first study vaccine administration Current tuberculosis prophylaxis or therapy Clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health Any medical, psychiatric, or social condition that would interfere with the study. More information about this criterion can be found in the protocol. Any job-related responsibility that would interfere with the study Serious adverse reaction to vaccines. A person who had an adverse reaction to pertussis vaccine as a child is not excluded. Autoimmune disease or immunodeficiency Active syphilis infection Unstable asthma Diabetes mellitus type 1 or 2 Thyroid disease requiring treatment Serious angioedema within the past 3 years Uncontrolled hypertension Bleeding disorder Cancer. If a participant has had surgery to remove the cancer and, in the opinion of the investigator, the cancer is not likely to recur during the study period, the participant is not excluded. Seizure disorder Asplenia Mental illness that would interfere with compliance with the protocol Other conditions that, in the judgment of the investigator, would interfere with the study Pregnant or breastfeeding

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>DNA HIV vaccine administered at study entry and at Months 1 and 2 and adenoviral vector HIV vaccine administered at Month 6 | Biological: VRC-HIVDNA016-00-VP<br>* 4 mg administered in deltoid<br>* Other names: Multiclade HIV-1 DNA Plasmid Vaccine;Biological: VRC-HIVADV014-00-VP<br>* 1 x 10^10 PU administered in deltoid<br>* Other names: rAD;|
| Placebo Comparator: 2<br>DNA HIV vaccine placebo administered at study entry and at Months 1 and 2 and adenoviral vector HIV vaccine placebo administered at Month 6 | Biological: VRC-HIVDNA016-00-VP placebo<br>* 1 mL administered at study entry and Months 1 and 2<br>* Other names: Phosphate buffered saline;Biological: VRC-HIVADV014-00-VP placebo<br>* 1 mL administered at Month 6<br>* Other names: VRC-DILUENT013-DIL-VP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local and systemic adverse reactions |  | Measured after each injection and for 12 months after the first injection | 
| Unfractionated IFN-γ ELISpot responses to HIV-1 peptide pools as performed by the VRC laboratory |  | Measured at Day 196 | 
| Unfractionated IFN-γ ELISpot responses to HIV-1 peptide pools as performed by the FHCRC laboratory |  | Measured at Day 210 | 
| CD4 and CD8 T cell responses to HIV-1 peptide pools as measured by flow cytometry-based intracellular cytokine staining (ICS) assay as performed by the VRC laboratory |  | Measured at Day 196 | 
| CD4 and CD8 T cell responses to HIV-1 peptide pools as measured by flow cytometry-based ICS assay as performed by the FHCRC laboratory |  | Measured at Day 210 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral immune response to HIV-1 as measured by neutralizing antibody and binding assays |  | Measured through Month 36 | 
| Unfractionated IFN-γ ELISpot responses to HIV-1 as performed by the FHCRC or the VRC laboratories |  | Measured at Days 70, 210, and 364 | 
| CD4 and CD8 T cell responses to HIV-1 as measured by flow cytometry-based ICS assay as performed by the FHCRC or the VRC laboratories |  | Measured at Days 70, 210, and 364 | 
| Vaccine-induced HIV-specific T cell responses to individual peptide pools as measured by IFN-γ ELISpot and ICS as performed by the FHCRC or the VRC laboratories |  | Measured through Month 36 | 
| Cross-clade cellular immune responses to HIV-1 Gag-Pol-Nef peptides from clades A and C as assessed by IFN-γ ELISpot and ICS assays as performed by the FHCRC or the VRC laboratories |  | Measured through Month 36 | 

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