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Safety of and Immune Response to an HIV Vaccine (VRC-HIVDNA009-00-VP) Administered With Interleukin-2/Immunoglobulin (IL-2/Ig) DNA Adjuvant in Uninfected Adults

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
VRC-HIVDNA009-00-VP (Gag-Pol-Nef-multiclade-Env) with adjuvant VRC-ADJDNA004-IL2-VP
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring HIV Seronegativity, HIV Preventive Vaccine, HIV-1, AIDS Vaccines, Vaccines, DNA, Dose-Response Relationship, Immunologic, Cytokines, Plasmids, Adjuvants, Immunologic, Drug Administration Schedule, Interleukin, IL2, Ig, IL@/Ig

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria HIV negative Willing to receive HIV test results Good general health Acceptable methods of contraception for females of reproductive potential Hepatitis B surface antigen negative Anti-hepatitis C virus antibody (anti-HCV) negative or negative HCV PCR if anti-HCV is positive Normal thyroid stimulating hormone (TSH) level Exclusion Criteria HIV vaccines or placebos 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 Clinical depression with pharmacological treatment within the past 2 years Active syphilis 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 Unstable asthma Type 1 or Type 2 Diabetes Mellitus Thyroid disease requiring treatment Serious angioedema within the past 3 years Uncontrolled hypertension Bleeding disorder Malignancy unless it has been surgically removed and, in the opinion of the investigator, is not likely to recur during the study period Seizure disorder requiring medication within the past 3 years Asplenia Mental illness that would interfere with compliance with the protocol Other conditions that, in the judgement of the investigator, would interfere with the study Pregnant or breast-feeding

Sites / Locations

  • Project Brave HIV Vaccine CRS
  • Brigham and Women's Hosp. CRS
  • Fenway Community Health Clinical Research Site (FCHCRS)
  • NY Blood Ctr./Bronx CRS
  • NY Blood Ctr./Union Square CRS
  • HIV Prevention & Treatment CRS
  • Miriam Hospital's HVTU

Outcomes

Primary Outcome Measures

Clinical observation and monitoring of hematological, chemical, and immunologic parameters
local and systemic adverse reactions after each injection and for 12 months after last injection

Secondary Outcome Measures

Full Information

First Posted
September 12, 2003
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
NCT00069030
Brief Title
Safety of and Immune Response to an HIV Vaccine (VRC-HIVDNA009-00-VP) Administered With Interleukin-2/Immunoglobulin (IL-2/Ig) DNA Adjuvant in Uninfected Adults
Official Title
A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of the HIV-1 DNA Vaccine VRC-HIVDNA009-00-VP (Gag-Pol-Nef-multiclade Env) With the Plasmid Cytokine Adjuvant VRC-ADJDNA004-IL2-VP (IL-2/Ig)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
December 2003 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
December 2006 (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
This study will test the safety of and immune system response to a new HIV vaccine. The vaccine in this study is made from HIV DNA produced in a laboratory. Only part of the virus's DNA is used in the vaccine and the vaccine itself cannot cause HIV infection or AIDS. In addition to HIV DNA, the vaccine contains interleukin-2 (IL-2) DNA fused to a portion of immunoglobulin (Ig) DNA. IL-2 is a chemical that stimulates the immune system and may improve response to the vaccine. Study hypothesis: The IL-2/Ig plasmid will be very well tolerated in humans.
Detailed Description
Over 90% of the 40 million people infected with HIV live in developing countries and have little or no access to antiretroviral medications. The worldwide HIV/AIDS epidemic will 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. The DNA vaccine in this study, VRC-HIVDNA009-00-VP (Gag-Pol-Nef-multiclade Env), uses multiple gene products to increase the breadth of the immune response across different HIV subtypes. The DNA plasmids in VRC-HIVDNA009-00-VP code for proteins from HIV subtypes A, B, and C, which together represent 90% of new HIV infections in the world. The study vaccine is administered with an adjuvant. The adjuvant is a DNA plasmid encoding interleukin 2 (IL-2) fused to the Fc portion of IgG for enhanced stability. This IL-2/Ig adjuvant may augment the immune system's response to the vaccine. Participants in this study will be randomly assigned to receive either the vaccine and adjuvant, the vaccine and placebo, the adjuvant and placebo, or placebo alone. All injections will be administered by needle-free injection in the upper arm. Participants will receive four does of vaccine: one at their first study visit and then at Months 1, 2, and 6. Participants will have a follow-up visit 2 days after each injection. Some participants may receive another injection at this follow-up visit. All study participants will be followed for 18 months and will have 16 to 20 study visits. Study visits will last 1/2 to 2 hours and will include blood and urine tests and a physical exam. Participants will also have six HIV tests over the course of the study.

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, HIV-1, AIDS Vaccines, Vaccines, DNA, Dose-Response Relationship, Immunologic, Cytokines, Plasmids, Adjuvants, Immunologic, Drug Administration Schedule, Interleukin, IL2, Ig, IL@/Ig

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
VRC-HIVDNA009-00-VP (Gag-Pol-Nef-multiclade-Env) with adjuvant VRC-ADJDNA004-IL2-VP
Primary Outcome Measure Information:
Title
Clinical observation and monitoring of hematological, chemical, and immunologic parameters
Title
local and systemic adverse reactions after each injection and for 12 months after last injection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria HIV negative Willing to receive HIV test results Good general health Acceptable methods of contraception for females of reproductive potential Hepatitis B surface antigen negative Anti-hepatitis C virus antibody (anti-HCV) negative or negative HCV PCR if anti-HCV is positive Normal thyroid stimulating hormone (TSH) level Exclusion Criteria HIV vaccines or placebos 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 Clinical depression with pharmacological treatment within the past 2 years Active syphilis 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 Unstable asthma Type 1 or Type 2 Diabetes Mellitus Thyroid disease requiring treatment Serious angioedema within the past 3 years Uncontrolled hypertension Bleeding disorder Malignancy unless it has been surgically removed and, in the opinion of the investigator, is not likely to recur during the study period Seizure disorder requiring medication within the past 3 years Asplenia Mental illness that would interfere with compliance with the protocol Other conditions that, in the judgement of the investigator, would interfere with the study Pregnant or breast-feeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raphael Dolin, MD
Organizational Affiliation
Harvard Medical School (HMS and HSDM)
Official's Role
Study Chair
Facility Information:
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
Fenway Community Health Clinical Research Site (FCHCRS)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
NY Blood Ctr./Bronx CRS
City
Bronx
State/Province
New York
ZIP/Postal Code
10456
Country
United States
Facility Name
NY Blood Ctr./Union Square CRS
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
HIV Prevention & Treatment CRS
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Miriam Hospital's HVTU
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
11039923
Citation
Barouch DH, Santra S, Schmitz JE, Kuroda MJ, Fu TM, Wagner W, Bilska M, Craiu A, Zheng XX, Krivulka GR, Beaudry K, Lifton MA, Nickerson CE, Trigona WL, Punt K, Freed DC, Guan L, Dubey S, Casimiro D, Simon A, Davies ME, Chastain M, Strom TB, Gelman RS, Montefiori DC, Lewis MG, Emini EA, Shiver JW, Letvin NL. Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination. Science. 2000 Oct 20;290(5491):486-92. doi: 10.1126/science.290.5491.486.
Results Reference
background
PubMed Identifier
9712056
Citation
Barouch DH, Santra S, Steenbeke TD, Zheng XX, Perry HC, Davies ME, Freed DC, Craiu A, Strom TB, Shiver JW, Letvin NL. Augmentation and suppression of immune responses to an HIV-1 DNA vaccine by plasmid cytokine/Ig administration. J Immunol. 1998 Aug 15;161(4):1875-82.
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
11371709
Citation
Approaches to the development of broadly protective HIV vaccines: challenges posed by the genetic, biological and antigenic variability of HIV-1: Report from a meeting of the WHO-UNAIDS Vaccine Advisory Committee Geneva, 21-23 February 2000. AIDS. 2001 Apr 13;15(6):W1-W25. No abstract available.
Results Reference
background
PubMed Identifier
9451748
Citation
Walker LG, Walker MB, Heys SD, Lolley J, Wesnes K, Eremin O. The psychological and psychiatric effects of rIL-2 therapy: a controlled clinical trial. Psychooncology. 1997 Dec;6(4):290-301. doi: 10.1002/(SICI)1099-1611(199712)6:43.0.CO;2-G.
Results Reference
background
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
21940420
Citation
Baden LR, Blattner WA, Morgan C, Huang Y, Defawe OD, Sobieszczyk ME, Kochar N, Tomaras GD, McElrath MJ, Russell N, Brandariz K, Cardinali M, Graham BS, Barouch DH, Dolin R; NIAID HIV Vaccine Trials Network 044 Study Team. Timing of plasmid cytokine (IL-2/Ig) administration affects HIV-1 vaccine immunogenicity in HIV-seronegative subjects. J Infect Dis. 2011 Nov 15;204(10):1541-9. doi: 10.1093/infdis/jir615. Epub 2011 Sep 21.
Results Reference
derived

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Safety of and Immune Response to an HIV Vaccine (VRC-HIVDNA009-00-VP) Administered With Interleukin-2/Immunoglobulin (IL-2/Ig) DNA Adjuvant in Uninfected Adults

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