Safety of and Immune Response to Two Different HIV Vaccines, Each Followed by a Adenoviral Vaccine Boost, in HIV Uninfected Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00270218
First received: December 21, 2005
Last updated: August 21, 2013
Last verified: August 2013
  Purpose

The purpose of this study is to determine the safety of and immune response to an adenoviral vector HIV vaccine or a DNA HIV vaccine, each followed by an adenoviral vector HIV vaccine boost, in HIV uninfected adults.


Condition Intervention Phase
HIV Infections
Biological: VRC-HIVADV014-00-VP
Biological: VRC-HIVDNA009-00-VP
Biological: FFB
Biological: PBS
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: A Phase I Clinical Trial to Evaluate Immune Response Kinetics and Safety of Two Different Primes, Adenoviral Vector Vaccine (VRC-HIVADV014-00-VP) and DNA Vaccine (VRC-HIVDNA009-00-VP), Each Followed by Adenoviral Vector Boost in Healthy, HIV-1 Uninfected Adults

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Safety (local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse and serious experiences) [ Time Frame: After each injection and for 6 months after the last injection ] [ Designated as safety issue: Yes ]
  • Magnitude of HIV-specific CD4+ and CD8+ T-cell responses, defined as percentage of T cells expressing IFN-gamma or IL-2 to vaccine peptide pools [ Time Frame: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination ] [ Designated as safety issue: No ]
  • Social impact (negative experiences or problems associated with participation in the study and other social, travel, work, school, health care, life insurance, health insurance, housing, military, or other impacts identified by the participant) [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Expression of HIV-specific T-cell memory differentiation markers and other markers of interest by flow cytometry [ Time Frame: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination ] [ Designated as safety issue: No ]
  • Titer to HIV-specific binding antibodies assessed by ELISA [ Time Frame: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination ] [ Designated as safety issue: No ]
  • Titer of HIV-specific neutralization antibodies assessed by neutralizing antibody assay, if indicated [ Time Frame: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination ] [ Designated as safety issue: No ]

Enrollment: 66
Study Start Date: February 2006
Study Completion Date: August 2007
Arms Assigned Interventions
Experimental: 1
Arm 1 participants will be given an injection of VRC-HIVADV014-00-VP vaccine on Days 0 and 168.
Biological: VRC-HIVADV014-00-VP
HIV-1 recombinant adenoviral vector vaccine given as a 1 mL intramuscular injection in the deltoid
Placebo Comparator: 2
Arm 2 participants will be given an injection of final formulation buffer (FFB) on Days 0 and 168.
Biological: FFB
Adenoviral vector FFB given as a 1 mL intramuscular injection in the deltoid
Experimental: 3
Arm 3 participants will be given an injection of VRC-HIVDNA009-00-VP vaccine on Days 0 and 28. Participants will also be given an injection of VRC-HIVADV014-00-VP on Day 168.
Biological: VRC-HIVADV014-00-VP
HIV-1 recombinant adenoviral vector vaccine given as a 1 mL intramuscular injection in the deltoid
Biological: VRC-HIVDNA009-00-VP
HIV-1 DNA plasmid vaccine given as a 1 mL intramuscular injection in the deltoid
Placebo Comparator: 4
Arm 4 participants will be given an injection of phosphate buffered saline (PBS) on Days 0 and 28 and an injection of FFB on Day 168.
Biological: FFB
Adenoviral vector FFB given as a 1 mL intramuscular injection in the deltoid
Biological: PBS
phosphate buffered saline

Detailed Description:

Evaluating the immunogenicity of HIV vaccines is critical to improving vaccine design and development. The adenoviral vector HIV vaccine VRC-HIVADV014-00-VP has shown immunogenicity in early studies and appeared safe and well tolerated at three different doses in a prior dose-escalation vaccine trial in HIV uninfected adults. 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 DNA plasmids in both vaccines code for proteins from HIV subtypes A, B, and C, which together represent 90% of new HIV infections. This study will determine the safety and immune response to the administration of an adenoviral vector HIV vaccine or a DNA HIV vaccine, each followed by an adenoviral vaccine boost, in HIV uninfected adults.

This study will last 1 year. Participants will be randomly assigned to one of two groups. Within each group, participants will be randomly assigned to receive either vaccine or control injections. Group 1 participants will receive either placebo or the adenoviral HIV vaccine at study entry and Month 6. Group 2 participants will receive either placebo or the DNA HIV vaccine at study entry and Month 1 and the adenoviral HIV vaccine at Month 6. Participants will be asked to record their temperatures and other side effects in a symptom log on the day of each vaccination and for 3 days thereafter to report any side effects.

Group 1 participants will have 16 study visits, and a physical exam and HIV and pregnancy prevention counseling will occur at each visit. Participants will also be asked about any side effects and medications they are taking. Blood collection will occur at most visits. Urine collection will occur at selected visits. Participants will be asked to complete a social impact assessment at Months 2, 6, and 12 and a testing and belief questionnaire at Months 6 and 12.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • HIV uninfected
  • Good general health
  • Pre-existing adenovirus 5 (Ad5) neutralizing antibody titers of less than a 1:12 ratio
  • 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
  • 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
  • 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
  • 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.
  • 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 reactions to vaccines, including hypersensitivity and related symptoms. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
  • Autoimmune disease or immunodeficiency
  • Active syphilis infection. Participants who have been fully treated for syphilis for more than 6 months prior to study entry are not excluded.
  • Moderate to severe asthma. More information on this criterion can be found in the protocol.
  • Type 1 or type 2 diabetes mellitus. Participants with histories of isolated gestational diabetes are not excluded.
  • Thyroid disease or surgical removal of the thyroid requiring medication during the 12 months prior to study entry
  • Accumulation of fluid in the blood vessels (angioedema) within 3 years prior to study entry if episodes are considered serious or have required medication in the 2 years prior to study entry
  • Uncontrolled hypertension
  • Body mass index (BMI) of 40 or greater OR BMI of 35 or greater if certain other criteria apply. More information about these criteria can be found in the protocol.
  • Bleeding disorder
  • Cancer. Participants with surgically removed cancer that is unlikely to recur are not excluded.
  • Seizure disorder
  • Absence of the spleen
  • Mental illness that would interfere with the study
  • Pregnancy or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00270218

Locations
United States, Alabama
Alabama Vaccine CRS
Birmingham, Alabama, United States, 35294-2041
United States, California
San Francisco Vaccine and Prevention CRS
San Francisco, California, United States, 94102
United States, New York
NY Blood Ctr./Union Square CRS
New York, New York, United States, 10003
HIV Prevention & Treatment CRS
New York, New York, United States, 10032
Univ. of Rochester HVTN CRS
Rochester, New York, United States, 14642-0001
United States, Tennessee
Vanderbilt Vaccine CRS
Nashville, Tennessee, United States, 37232
United States, Washington
FHCRC/UW Vaccine CRS
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Investigators
Study Chair: Stephen De Rosa, MD Fred Hutchinson Cancer Research Center and University of Washington
Study Chair: Spyros A. Kalams, MD Vanderbilt University
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00270218     History of Changes
Other Study ID Numbers: HVTN 068, 10060
Study First Received: December 21, 2005
Last Updated: August 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV Seronegativity
Adenoviral Vector Vaccine
DNA Plasmid Vaccine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on July 26, 2014