Clinical trial NCT00125970: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV Seronegativity
HIV Preventive Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2005-08-02
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Local and systemic adverse reactions
timeFrame: Measured after each injection and for 12 months after the first injection
measure: Unfractionated IFN-γ ELISpot responses to HIV-1 peptide pools as performed by the VRC laboratory
timeFrame: Measured at Day 196
measure: Unfractionated IFN-γ ELISpot responses to HIV-1 peptide pools as performed by the FHCRC laboratory
timeFrame: Measured at Day 210
measure: 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
timeFrame: Measured at Day 196
measure: 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
timeFrame: Measured at Day 210
Secondary outcomes:
measure: Humoral immune response to HIV-1 as measured by neutralizing antibody and binding assays
timeFrame: Measured through Month 36
measure: Unfractionated IFN-γ ELISpot responses to HIV-1 as performed by the FHCRC or the VRC laboratories
timeFrame: Measured at Days 70, 210, and 364
measure: 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
timeFrame: Measured at Days 70, 210, and 364
measure: 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
timeFrame: Measured through Month 36
measure: 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
timeFrame: Measured through Month 36
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Vaccine CRS
state: Alabama
city: Baltimore
country: United States
facility: Project Brave HIV Vaccine CRS
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hosp. CRS
state: Massachusetts
city: Providence
country: United States
facility: Miriam Hospital's HVTU
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt Vaccine CRS
state: Tennessee
city: Rio de Janeiro
country: Brazil
facility: Projeto Praca Onze/Hesfa Crs
city: San Paulo
country: Brazil
facility: Sao Paulo HVTU - CRT DST/AIDS CRS
city: Port-au-Prince
country: Haiti
facility: Les Centres GHESKIO CRS
city: Kingston
country: Jamaica
facility: Epidemiology Research & Training Unit Jamaica MOH CRS
city: Johannesburg
country: South Africa
facility: Soweto HVTN CRS
state: Gauteng
city: Cape Town
country: South Africa
facility: Emavundleni Desmond Tutu HIV Centre CRS
city: Klerksdorp
country: South Africa
facility: CAPRISA Aurum CRS
Study officials:
affiliation: University of Rochester
name: Michael Keefer, MD
role: STUDY_CHAIR
affiliation: Aurum Health Research Limited
name: Gavin Churchyard, MBBCh, FCP, MMed, PhD
role: STUDY_CHAIR
References:
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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.
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.
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.