Study of an HIV Preventive Vaccine Given With or Without an Adjuvant in HIV Uninfected Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00111605
First received: May 23, 2005
Last updated: September 7, 2012
Last verified: September 2012
  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 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
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

Resource links provided by NLM:


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 Completion Date: May 2008
Arms Assigned Interventions
Experimental: 1
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.

Experimental: 2
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.

Experimental: 3
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.

Experimental: 4
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.

Experimental: 5
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.

Experimental: 6
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.

Experimental: 7
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Alabama
Alabama Vaccine CRS
Birmingham, Alabama, United States, 35294-2041
United States, Maryland
Project Brave HIV Vaccine CRS
Baltimore, Maryland, United States, 21201
United States, Tennessee
Vanderbilt Vaccine CRS
Nashville, Tennessee, United States, 37232
Thailand
Chiang Mai Univ. HVTN CRS
Chiang Mai, Thailand
Sponsors and Collaborators
Investigators
Study Chair: Spyros Kalams, MD Vanderbilt University
Study Chair: Scott Parker, MD University of Alabama at Birmingham
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00111605     History of Changes
Other Study ID Numbers: HVTN 060, 10057
Study First Received: May 23, 2005
Last Updated: September 7, 2012
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

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

ClinicalTrials.gov processed this record on October 16, 2014