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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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
VRC-HIVDNA016-00-VP
VRC-HIVADV014-00-VP
VRC-HIVDNA016-00-VP placebo
VRC-HIVADV014-00-VP placebo
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring HIV Seronegativity, HIV Preventive Vaccine

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Alabama Vaccine CRS
  • Project Brave HIV Vaccine CRS
  • Brigham and Women's Hosp. CRS
  • Miriam Hospital's HVTU
  • Vanderbilt Vaccine CRS
  • Projeto Praca Onze/Hesfa Crs
  • Sao Paulo HVTU - CRT DST/AIDS CRS
  • Les Centres GHESKIO CRS
  • Epidemiology Research & Training Unit Jamaica MOH CRS
  • Soweto HVTN CRS
  • Emavundleni Desmond Tutu HIV Centre CRS
  • CAPRISA Aurum CRS

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1

2

Arm Description

DNA HIV vaccine administered at study entry and at Months 1 and 2 and adenoviral vector HIV vaccine administered at Month 6

DNA HIV vaccine placebo administered at study entry and at Months 1 and 2 and adenoviral vector HIV vaccine placebo administered at Month 6

Outcomes

Primary Outcome Measures

Local and systemic adverse reactions
Unfractionated IFN-γ ELISpot responses to HIV-1 peptide pools as performed by the VRC laboratory
Unfractionated IFN-γ ELISpot responses to HIV-1 peptide pools as performed by the FHCRC laboratory
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
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

Secondary Outcome Measures

Humoral immune response to HIV-1 as measured by neutralizing antibody and binding assays
Unfractionated IFN-γ ELISpot responses to HIV-1 as performed by the FHCRC or the VRC laboratories
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
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
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

Full Information

First Posted
June 30, 2005
Last Updated
October 13, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00125970
Brief Title
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
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
February 2008 (Actual)
Study Completion Date
January 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
HIV Seronegativity, HIV Preventive Vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
480 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
DNA HIV vaccine administered at study entry and at Months 1 and 2 and adenoviral vector HIV vaccine administered at Month 6
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
DNA HIV vaccine placebo administered at study entry and at Months 1 and 2 and adenoviral vector HIV vaccine placebo administered at Month 6
Intervention Type
Biological
Intervention Name(s)
VRC-HIVDNA016-00-VP
Other Intervention Name(s)
Multiclade HIV-1 DNA Plasmid Vaccine
Intervention Description
4 mg administered in deltoid
Intervention Type
Biological
Intervention Name(s)
VRC-HIVADV014-00-VP
Other Intervention Name(s)
rAD
Intervention Description
1 x 10^10 PU administered in deltoid
Intervention Type
Biological
Intervention Name(s)
VRC-HIVDNA016-00-VP placebo
Other Intervention Name(s)
DNA HIV placebo vaccine, Phosphate buffered saline
Intervention Description
1 mL administered at study entry and Months 1 and 2
Intervention Type
Biological
Intervention Name(s)
VRC-HIVADV014-00-VP placebo
Other Intervention Name(s)
rAD placebo, VRC-DILUENT013-DIL-VP
Intervention Description
1 mL administered at Month 6
Primary Outcome Measure Information:
Title
Local and systemic adverse reactions
Time Frame
Measured after each injection and for 12 months after the first injection
Title
Unfractionated IFN-γ ELISpot responses to HIV-1 peptide pools as performed by the VRC laboratory
Time Frame
Measured at Day 196
Title
Unfractionated IFN-γ ELISpot responses to HIV-1 peptide pools as performed by the FHCRC laboratory
Time Frame
Measured at Day 210
Title
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
Title
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
Secondary Outcome Measure Information:
Title
Humoral immune response to HIV-1 as measured by neutralizing antibody and binding assays
Time Frame
Measured through Month 36
Title
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
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Keefer, MD
Organizational Affiliation
University of Rochester
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Gavin Churchyard, MBBCh, FCP, MMed, PhD
Organizational Affiliation
Aurum Health Research Limited
Official's Role
Study Chair
Facility Information:
Facility Name
Alabama Vaccine CRS
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-2041
Country
United States
Facility Name
Project Brave HIV Vaccine CRS
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Brigham and Women's Hosp. CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Miriam Hospital's HVTU
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02115
Country
United States
Facility Name
Vanderbilt Vaccine CRS
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Projeto Praca Onze/Hesfa Crs
City
Rio de Janeiro
Country
Brazil
Facility Name
Sao Paulo HVTU - CRT DST/AIDS CRS
City
San Paulo
Country
Brazil
Facility Name
Les Centres GHESKIO CRS
City
Port-au-Prince
Country
Haiti
Facility Name
Epidemiology Research & Training Unit Jamaica MOH CRS
City
Kingston
Country
Jamaica
Facility Name
Soweto HVTN CRS
City
Johannesburg
State/Province
Gauteng
Country
South Africa
Facility Name
Emavundleni Desmond Tutu HIV Centre CRS
City
Cape Town
Country
South Africa
Facility Name
CAPRISA Aurum CRS
City
Klerksdorp
Country
South Africa

12. IPD Sharing Statement

Citations:
PubMed Identifier
12699356
Citation
Esparza J, Osmanov S. HIV vaccines: a global perspective. Curr Mol Med. 2003 May;3(3):183-93. doi: 10.2174/1566524033479825.
Results Reference
background
PubMed Identifier
12089434
Citation
Gaschen B, Taylor J, Yusim K, Foley B, Gao F, Lang D, Novitsky V, Haynes B, Hahn BH, Bhattacharya T, Korber B. Diversity considerations in HIV-1 vaccine selection. Science. 2002 Jun 28;296(5577):2354-60. doi: 10.1126/science.1070441.
Results Reference
background
PubMed Identifier
11390574
Citation
Moore JP, Parren PW, Burton DR. Genetic subtypes, humoral immunity, and human immunodeficiency virus type 1 vaccine development. J Virol. 2001 Jul;75(13):5721-9. doi: 10.1128/JVI.75.13.5721-5729.2001. No abstract available.
Results Reference
background
PubMed Identifier
14738219
Citation
Stratov I, DeRose R, Purcell DF, Kent SJ. Vaccines and vaccine strategies against HIV. Curr Drug Targets. 2004 Jan;5(1):71-88. doi: 10.2174/1389450043490686.
Results Reference
background
PubMed Identifier
34843602
Citation
Fischinger S, Cizmeci D, Deng D, Grant SP, Frahm N, McElrath J, Fuchs J, Bart PA, Pantaleo G, Keefer M, O Hahn W, Rouphael N, Churchyard G, Moodie Z, Donastorg Y, Streeck H, Alter G. Sequence and vector shapes vaccine induced antibody effector functions in HIV vaccine trials. PLoS Pathog. 2021 Nov 29;17(11):e1010016. doi: 10.1371/journal.ppat.1010016. eCollection 2021 Nov.
Results Reference
derived
PubMed Identifier
25820067
Citation
Jin X, Morgan C, Yu X, DeRosa S, Tomaras GD, Montefiori DC, Kublin J, Corey L, Keefer MC; NIAID HIV Vaccine Trials Network. Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials. Vaccine. 2015 May 11;33(20):2347-53. doi: 10.1016/j.vaccine.2015.03.036. Epub 2015 Mar 25.
Results Reference
derived
PubMed Identifier
21857901
Citation
Churchyard GJ, Morgan C, Adams E, Hural J, Graham BS, Moodie Z, Grove D, Gray G, Bekker LG, McElrath MJ, Tomaras GD, Goepfert P, Kalams S, Baden LR, Lally M, Dolin R, Blattner W, Kalichman A, Figueroa JP, Pape J, Schechter M, Defawe O, De Rosa SC, Montefiori DC, Nabel GJ, Corey L, Keefer MC; NIAID HIV Vaccine Trials Network. A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204). PLoS One. 2011;6(8):e21225. doi: 10.1371/journal.pone.0021225. Epub 2011 Aug 3.
Results Reference
derived

Learn more about this trial

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

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