Study of an HIV Preventive Vaccine Given With or Without an Adjuvant in HIV Uninfected Adults - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00111605

Purpose

The purpose of this study is to evaluate the safety and tolerability of an experimental HIV vaccine. The vaccine will be given with or without IL-12 DNA adjuvant (at three escalating doses of 100, 500, and 1,500 mcg respectively), a substance that helps the body respond to a vaccine. This study will also determine the safety and tolerability of an experimental HIV vaccine boosted with two adjuvants.

Condition	Intervention	Phase
HIV Infections	Biological: HIV-1 gag DNA Biological: HIV-1 gag DNA plus IL-12 DNA adjuvant Biological: CTL MEP/RC529-SE/GM-CSF (CTL MEP vaccine) Biological: Sodium chloride injection (0.9%)	Phase I

MedlinePlus related topics: AIDS

Drug Information available for: Sargramostim Granulocyte-macrophage colony-stimulating factor Sodium chloride Chlorides Interleukin-12

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety Study
Official Title:	A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of an HIV-1 Gag DNA Vaccine With or Without IL-12 DNA Adjuvant, Boosted With Homologous Plasmids in Healthy, HIV-1 Uninfected Adult Participants

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

Primary Outcome Measures:

Safety, as judged by local and systemic reactogenicity signs and symptoms, laboratory measures of safety, and adverse and serious experiences [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Immunogenicity, as judged by HIV-specific cellular responses assessed by interferon-gamma ELISpot assays and by intracellular cytokine staining (ICS) [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]

Enrollment:	144
Study Start Date:	August 2005
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental HIV gag DNA vaccine or placebo on Days 0, 28, and 84	Biological: HIV-1 gag DNA A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid Biological: Sodium chloride injection (0.9%) All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid. Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.
2: Experimental HIV gag DNA vaccine plus 100 mcg of IL-12 or placebo on Days 0, 28, and 84	Biological: HIV-1 gag DNA A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid Biological: HIV-1 gag DNA plus IL-12 DNA adjuvant Injection IL-12 DNA adjuvant intramuscularly into the deltoid Biological: Sodium chloride injection (0.9%) All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid. Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.
3: Experimental HIV gag DNA vaccine plus 500 mcg of IL-12 or placebo on Days 0, 28, and 84	Biological: HIV-1 gag DNA A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid Biological: HIV-1 gag DNA plus IL-12 DNA adjuvant Injection IL-12 DNA adjuvant intramuscularly into the deltoid Biological: Sodium chloride injection (0.9%) All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid. Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.
4: Experimental HIV gag DNA vaccine plus 1,500 mcg of IL-12 or placebo on Days 0, 28, and 84	Biological: HIV-1 gag DNA A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid Biological: HIV-1 gag DNA plus IL-12 DNA adjuvant Injection IL-12 DNA adjuvant intramuscularly into the deltoid Biological: Sodium chloride injection (0.9%) All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid. Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.
5: Experimental HIV gag DNA vaccine or placebo on Days 0, 28, 84, 168, and 273	Biological: HIV-1 gag DNA A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid Biological: Sodium chloride injection (0.9%) All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid. Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.
6: Experimental HIV gag DNA vaccine plus IL-12 or placebo on Days 0, 28, and 84 plus CTL MEP/RC529-SE/GM-SCF booster vaccine on Days 168 and 273	Biological: HIV-1 gag DNA A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid Biological: HIV-1 gag DNA plus IL-12 DNA adjuvant Injection IL-12 DNA adjuvant intramuscularly into the deltoid Biological: CTL MEP/RC529-SE/GM-CSF (CTL MEP vaccine) A 1 mL intramuscular injection in the deltoid Biological: Sodium chloride injection (0.9%) All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid. Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.
7: Experimental HIV gag DNA vaccine plus IL-12 DNA adjuvant or placebo on Days 0 and 84	Biological: HIV-1 gag DNA A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid Biological: Sodium chloride injection (0.9%) All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid. Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

Detailed Description:

The HIV epidemic is a major global health challenge, causing tremendous human suffering and economic loss throughout the world. The need for a safe, effective, and affordable HIV preventive vaccine is critical. This study will determine the safety and immunogenicity of an experimental HIV vaccine, HIV-1 gag DNA, given with or without an IL-12 adjuvant and boosted HIV-1 gag DNA with or without IL-12 DNA adjuvant.

This study will comprise two parts (Parts A and B). Part A will last 9 months and Part B, 15 months. Part A will consist of 48 participants enrolled in 4 groups. Group 1 participants will be randomly assigned to receive the gag DNA vaccine or placebo. Participants in Groups 2, 3, and 4 will be randomly assigned to receive the gag DNA vaccine and either 100 mcg, 500 mcg, or 1,500 mcg IL-12 DNA or placebo. Vaccinations for Groups 1 through 4 will be given intramuscularly and will occur at study entry and at Months 1 and 3.

Part B will consist of 96 participants, enrolled in 3 groups. Participants in Part B will receive their first vaccination 2 weeks after Part A participants receive their second vaccination. Group 5 participants will receive either the HIV-1 gag DNA vaccine or placebo. Group 6 participants will receive either the HIV-1 gag DNA vaccine plus IL-12 DNA or placebo. Vaccinations for Groups 5 and 6 will occur at study entry and at Months 1, 3, 6, and 9. Group 7 participants will receive either the gag DNA vaccine plus IL-12 DNA or placebo at study entry and at Months 1 and 3. Throughout the study, blood and urine collections will occur, physical exams will be conducted, HIV testing and counseling will be offered, and interviews and questionnaires will be completed.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

HIV uninfected
Access to a participating HIV Vaccine Trials Unit (HVTU)
Willing to receive HIV test results
Willing and able to comply with all study requirements
In good general health
Willing to use acceptable methods of contraception for at least 21 days prior to study entry and until the last study visit. More information about this criterion can be found in the protocol.
Hepatitis B surface antigen negative
Anti-hepatitis C virus (anti-HCV) antibody negative or negative HCV PCR if anti-HCV antibody is positive
Weighs of or greater than 110 pounds (50 kg)

Exclusion Criteria:

HIV infection
HIV vaccines or placebos in prior HIV trial
Immunosuppressive medications within 168 days prior to first study vaccination
Blood products within 120 days prior to first study vaccination
Live attenuated vaccines within 30 days prior to first study vaccination
Medically indicated subunit or killed vaccines within 14 days prior to first study vaccination
Pneumococcal vaccine within 14 days prior to first study vaccination
Allergy treatment with antigen injections within 30 days prior to first study vaccination
Current anti-tuberculosis (TB) preventive therapy or treatment
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
Allergies to local amide-type anesthetics
Serious adverse reactions to vaccines, including hypersensitivity and related symptoms. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
Autoimmune disease or immunodeficiency
Active syphilis infection. Participants who have been fully treated for syphilis over 6 months prior to study entry are not excluded.
Moderate to severe asthma. More information on this criterion can be found in the protocol.
Type 1 or type 2 diabetes mellitus. Participants with histories of isolated gestational diabetes are not excluded.
Thyroid disease or surgical removal of the thyroid requiring medication during the 12 months prior to study entry
Accumulation of fluid in the blood vessels (angioedema) within 3 years prior to study entry, with episodes requiring medication in the 2 years prior to study entry
Hypertension that is not well controlled by medication OR blood pressure of 150/100 or higher at study entry
Body mass index (BMI) of 40 or greater OR BMI of 35 or greater, if certain criteria are met. More information about these criteria can be found in the protocol.
Bleeding disorder
Cancer. Participants with surgically removed cancer that, in the opinion of the investigator, is unlikely to recur are not excluded.
Absence of the spleen
Plans to become pregnant during the study
Pregnancy or breastfeeding

Exclusion Criterion for Participants in Part B:

Allergies to yeast-derived products

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00111605

Locations

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-2041
United States, Maryland
University of Maryland - Institute of Human Virology
Baltimore, Maryland, United States, 21201
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Thailand
Research Institute for Health Sciences (RIHES)
Chiang Mai, Thailand

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	Spyros Kalams, MD	Vanderbilt University
Study Chair:	Scott Parker, MD	University of Alabama at Birmingham

More Information

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

Publications:

Bolesta E, Gzyl J, Wierzbicki A, Kmieciak D, Kowalczyk A, Kaneko Y, Srinivasan A, Kozbor D. Clustered epitopes within the Gag-Pol fusion protein DNA vaccine enhance immune responses and protection against challenge with recombinant vaccinia viruses expressing HIV-1 Gag and Pol antigens. Virology. 2005 Feb 20;332(2):467-79.

Letvin NL. Progress toward an HIV vaccine. Annu Rev Med. 2005;56:213-23. Review.

Sha BE, Onorato M, Bartlett JA, Bosch RJ, Aga E, Nokta M, Adams EM, Li XD, Eldridge J, Pollard RB. Safety and immunogenicity of a polyvalent peptide C4-V3 HIV vaccine in conjunction with IL-12. AIDS. 2004 May 21;18(8):1203-6.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	HVTN 060
Study First Received:	May 23, 2005
Last Updated:	June 30, 2008
ClinicalTrials.gov Identifier:	NCT00111605
Health Authority:	United States: Food and Drug Administration

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

AIDS Vaccines
HIV Vaccines
HIV Preventive Vaccine
HIV Seronegativity

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
Interleukin-12
HIV Infections
Sexually Transmitted Diseases

Acquired Immunodeficiency Syndrome
Healthy
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
Lentivirus Infections
Infection

ClinicalTrials.gov processed this record on January 16, 2009