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 - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00069030

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Biological: VRC-HIVDNA009-00-VP (Gag-Pol-Nef-multiclade-Env) with adjuvant VRC-ADJDNA004-IL2-VP	Phase I

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Prevention
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)

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Interleukin-2

U.S. FDA Resources

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

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

Estimated Enrollment:

70

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.

Eligibility

Ages Eligible for Study:	18 Years to 40 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00069030

Locations

United States, Maryland
Institute of Human Virology, University of Maryland at Baltimore
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Harvard Medical School/Brigham and Womens' Hospital
Boston, Massachusetts, United States, 02115
United States, New York
New York Blood Center - Bronx
Bronx, New York, United States, 10456
New York Blood Center - Union Square
New York, New York, United States, 10003

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:

Raphael Dolin, MD

Harvard University

More Information

Additional Information:

Click here for more information on HIV preventive vaccines This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Publications:

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.

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.

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. Review. No abstract available.

[No authors listed] 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.

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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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;204(10):1541-9. Epub 2011 Sep 21.

ClinicalTrials.gov Identifier:	NCT00069030 History of Changes
Other Study ID Numbers:	HVTN 044, 5K08AI051223-03
Study First Received:	September 12, 2003
Last Updated:	October 28, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

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

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
Adjuvants, Immunologic

Interleukin-2
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 12, 2012