A Phase Ib Clinical Trial to Compare the Safety, Tolerability, and Immunogenicity of an HIV-1 Adenoviral Vector Boost Administered Intramuscularly, Intradermally, or Subcutaneously After an HIV-1 DNA Plasmid Vaccine Prime Administered Intramuscularly to Healthy Adenovirus Type 5 Seropositive HIV-1-Uninfected Adults

National Institute of Allergy and Infectious Diseases (NIAID)7 sites in 2 countries90 target enrollmentNovember 2006

ConditionsHIV Infections

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Enrollment: 90
Locations: 7
Primary Endpoint: Magnitude of HIV-specific T-cell responses assessed by the magnitude of IFN-gamma enzyme-linked immunosorbent spot (ELISpot) responses
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to determine the safety of, immune response to, and tolerability of an adenoviral vector HIV vaccine given after a three-dose regimen of a DNA HIV vaccine. The adenoviral vaccine will be given into arm muscle (intramuscularly), between skin layers (intradermally), or under the skin (subcutaneously).

NOTE: In October 2007, vaccinations with the adenoviral vaccine, VRC-HIVADV014-00-VP, were discontinued. In December 2007, vaccinations with the DNA vaccine were also discontinued. Participants will be followed for safety and immune responses at regular study visits.

Detailed Description

One factor that may affect safety and immunogenicity to an HIV vaccine is the route of vaccine administration. Administration into the skin (intradermal) or subcutaneous tissue may be more immunogenic or provide a different pattern of immune responses than administration by the intramuscular route. Previous studies with other preventive vaccines suggest that the resulting immunogenicity following intradermal or subcutaneous vaccine administration is comparable or better than immunogenicity observed following intramuscular administration. Increased immunogenicity though use of a particular route will likely result in greater demonstrated efficacy, requiring fewer or lower doses of vaccine to elicit a sufficient immune response. The DNA HIV vaccine VRC-HIVDNA009-00-VP has shown immunogenicity in multiple clinical trials; in one trial, the DNA vaccine demonstrated a nearly 100% CD4 T-cell response rate. The adenoviral vector HIV vaccine VRC-HIVADV014-00-VP has shown immunogenicity when given intramuscularly and has appeared safe and well tolerated in prior vaccine trials in HIV uninfected adults. The DNA plasmids in both vaccines code for proteins from HIV subtypes A, B, and C. This study will evaluate the safety, immunogenicity, and tolerability to a DNA HIV vaccine, followed by an adenoviral vaccine boost given either intramuscularly, intradermally, or subcutaneously, in HIV uninfected adults. All participants will receive three doses of the DNA vaccine intramuscularly at study entry and Months 1 and 2. Participants will be randomly assigned to one of three groups, differing by how they will receive the adenoviral vaccine boost: * Group 1 participants will receive the vaccine boost intramuscularly at Month 6 * Group 2 participants will receive the vaccine boost intradermally at Month 6 * Group 3 participants will receive the vaccine boost subcutaneously at Month 6 This study will last 1 year. There will be 12 study visits; a physical exam, medication history, and risk reduction/pregnancy prevention compliance counseling will occur at all visits. Urine and blood collection will occur at selected visits. Participants will be asked to complete a social impact assessment at Months 2, 6, and 12 and an outside testing and belief questionnaire at Months 6 and 12. Participants will be asked to record their temperature and other side effects in a symptom log on the day of each vaccination and for 3 days thereafter to report any side effects. NOTE: In October 2007, vaccinations with the adenoviral vaccine, VRC-HIVADV014-00-VP, were discontinued. In December 2007, vaccinations with the DNA vaccine were also discontinued. Participants will be followed for safety and immune responses at regular study visits and will be asked to continue in long term follow-up for purposes of safety surveillance to a total of 5 years following initial vaccination

Registry

clinicaltrials.gov

Start Date

November 2006

End Date

December 2012

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•HIV-1 and -2 uninfected
•Good general health
•Pre-existing adenovirus 5 (Ad5) neutralizing antibody titers of a 1:12 ratio or greater
•Hepatitis B surface antigen negative
•Anti-hepatitis C virus (anti-HCV) antibody negative or negative HCV PCR if anti-HCV antibody is positive
•Have access to a participating HIV Vaccine Trials Unit (HVTU) and are willing to be followed during the study
•Willing to receive HIV test results
•Able to understand the vaccination procedure
•Willing to use acceptable forms of contraception

Exclusion Criteria

•HIV vaccines or placebos in prior HIV trial. Participants who can provide documentation that they received a placebo in a prior HIV trial may be eligible.
•Immunosuppressive medications within 168 days prior to first study vaccination
•Blood products within 120 days prior to first study vaccination
•Immunoglobulin within 60 days prior to first study vaccination
•Live attenuated vaccines within 30 days prior to first study vaccination
•Investigational research agents within 30 days prior to first study vaccination
•Medically indicated subunit or killed vaccines within 14 days prior to first study vaccination
•Allergy treatment with antigen injections within 30 days prior to first study vaccination
•Current anti-tuberculosis (TB) preventive therapy or treatment
•Clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health. More information about this criterion can be found in the protocol.