Safety of and Immune Response to a DNA HIV Vaccine Followed By an Adenoviral Vector HIV Vaccine in Healthy Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00125970
First received: June 30, 2005
Last updated: November 7, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Biological: VRC-HIVDNA016-00-VP
Biological: VRC-HIVADV014-00-VP
Biological: VRC-HIVDNA016-00-VP placebo
Biological: VRC-HIVADV014-00-VP placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Prevention
Official Title: 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, VRC-HIVADV014-00-VP, in HIV-1 Uninfected Adult Participants

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Local and systemic adverse reactions [ Time Frame: Measured after each injection and for 12 months after the first injection ] [ Designated as safety issue: Yes ]
  • Unfractionated IFN-γ ELISpot responses to HIV-1 peptide pools as performed by the VRC laboratory [ Time Frame: Measured at Day 196 ] [ Designated as safety issue: No ]
  • Unfractionated IFN-γ ELISpot responses to HIV-1 peptide pools as performed by the FHCRC laboratory [ Time Frame: Measured at Day 210 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Measured at Day 196 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Measured at Day 210 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Humoral immune response to HIV-1 as measured by neutralizing antibody and binding assays [ Time Frame: Measured through Month 36 ] [ Designated as safety issue: No ]
  • Unfractionated IFN-γ ELISpot responses to HIV-1 as performed by the FHCRC or the VRC laboratories [ Time Frame: Measured at Days 70, 210, and 364 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Measured at Days 70, 210, and 364 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Measured through Month 36 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Measured through Month 36 ] [ Designated as safety issue: No ]

Enrollment: 480
Study Start Date: September 2005
Study Completion Date: January 2010
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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
4 mg administered in deltoid
Other Name: Multiclade HIV-1 DNA Plasmid Vaccine
Biological: VRC-HIVADV014-00-VP
1 x 10^10 PU administered in deltoid
Other Name: rAD
Placebo Comparator: 2
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
1 mL administered at study entry and Months 1 and 2
Other Names:
  • DNA HIV placebo vaccine
  • Phosphate buffered saline
Biological: VRC-HIVADV014-00-VP placebo
1 mL administered at Month 6
Other Names:
  • rAD placebo
  • VRC-DILUENT013-DIL-VP

Detailed Description:

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.

  Eligibility

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

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
  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: NCT00125970

Locations
United States, Alabama
Alabama Vaccine CRS
Birmingham, Alabama, United States, 35294-2041
United States, Maryland
Project Brave HIV Vaccine CRS
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Brigham and Women's Hosp. CRS
Boston, Massachusetts, United States, 02115
United States, Rhode Island
Miriam Hospital's HVTU
Providence, Rhode Island, United States, 02115
United States, Tennessee
Vanderbilt Vaccine CRS
Nashville, Tennessee, United States, 37232
Brazil
Projeto Praca Onze/Hesfa Crs
Rio de Janeiro, Brazil
Sao Paulo HVTU - CRT DST/AIDS CRS
San Paulo, Brazil
Haiti
Les Centres GHESKIO CRS
Port-au-Prince, Haiti
Jamaica
Epidemiology Research & Training Unit Jamaica MOH CRS
Kingston, Jamaica
South Africa
Soweto HVTN CRS
Johannesburg, Gauteng, South Africa
Emavundleni Desmond Tutu HIV Centre CRS
Cape Town, South Africa
CAPRISA Aurum CRS
Klerksdorp, South Africa
Sponsors and Collaborators
Investigators
Study Chair: Michael Keefer, MD University of Rochester
Study Chair: Gavin Churchyard, MBBCh, FCP, MMed, PhD Aurum Health Research Limited
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00125970     History of Changes
Other Study ID Numbers: HVTN 204, 10061
Study First Received: June 30, 2005
Last Updated: November 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV Seronegativity
HIV Preventive 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 28, 2014