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

NCT ID: NCT00125970

Last Updated: 2021-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

480 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-09-30

Study Completion Date

2010-01-31

Brief Summary

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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

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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.

Conditions

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HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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1

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

Group Type EXPERIMENTAL

VRC-HIVDNA016-00-VP

Intervention Type BIOLOGICAL

4 mg administered in deltoid

VRC-HIVADV014-00-VP

Intervention Type BIOLOGICAL

1 x 10\^10 PU administered in deltoid

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

Group Type PLACEBO_COMPARATOR

VRC-HIVDNA016-00-VP placebo

Intervention Type BIOLOGICAL

1 mL administered at study entry and Months 1 and 2

VRC-HIVADV014-00-VP placebo

Intervention Type BIOLOGICAL

1 mL administered at Month 6

Interventions

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VRC-HIVDNA016-00-VP

4 mg administered in deltoid

Intervention Type BIOLOGICAL

VRC-HIVADV014-00-VP

1 x 10\^10 PU administered in deltoid

Intervention Type BIOLOGICAL

VRC-HIVDNA016-00-VP placebo

1 mL administered at study entry and Months 1 and 2

Intervention Type BIOLOGICAL

VRC-HIVADV014-00-VP placebo

1 mL administered at Month 6

Intervention Type BIOLOGICAL

Other Intervention Names

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Multiclade HIV-1 DNA Plasmid Vaccine rAD DNA HIV placebo vaccine Phosphate buffered saline rAD placebo VRC-DILUENT013-DIL-VP

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Keefer, MD

Role: STUDY_CHAIR

University of Rochester

Gavin Churchyard, MBBCh, FCP, MMed, PhD

Role: STUDY_CHAIR

Aurum Health Research Limited

Locations

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Alabama Vaccine CRS

Birmingham, Alabama, United States

Site Status

Project Brave HIV Vaccine CRS

Baltimore, Maryland, United States

Site Status

Brigham and Women's Hosp. CRS

Boston, Massachusetts, United States

Site Status

Miriam Hospital's HVTU

Providence, Rhode Island, United States

Site Status

Vanderbilt Vaccine CRS

Nashville, Tennessee, United States

Site Status

Projeto Praca Onze/Hesfa Crs

Rio de Janeiro, , Brazil

Site Status

Sao Paulo HVTU - CRT DST/AIDS CRS

São Paulo, , Brazil

Site Status

Les Centres GHESKIO CRS

Port-au-Prince, , Haiti

Site Status

Epidemiology Research & Training Unit Jamaica MOH CRS

Kingston, , Jamaica

Site Status

Soweto HVTN CRS

Johannesburg, Gauteng, South Africa

Site Status

Emavundleni Desmond Tutu HIV Centre CRS

Cape Town, , South Africa

Site Status

CAPRISA Aurum CRS

Klerksdorp, , South Africa

Site Status

Countries

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United States Brazil Haiti Jamaica South Africa

References

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Esparza J, Osmanov S. HIV vaccines: a global perspective. Curr Mol Med. 2003 May;3(3):183-93. doi: 10.2174/1566524033479825.

Reference Type BACKGROUND
PMID: 12699356 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12089434 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11390574 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14738219 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34843602 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25820067 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21857901 (View on PubMed)

Other Identifiers

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10061

Identifier Type: REGISTRY

Identifier Source: secondary_id

HVTN 204

Identifier Type: -

Identifier Source: org_study_id