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 1500 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 another experimental vaccine and 3 other adjuvants.

Study hypothesis:

Condition	Treatment or Intervention	Phase
HIV Infections	Vaccine: HIV-1 gag DNA  Vaccine: HIV CTL multiepitope peptide (MEP) with RC529-SE and GM-CSF adjuvants  Drug: IL-12 DNA adjuvant	Phase I

Further Study Details: 

Primary Outcomes: Safety, as judged by local and systemic reactogenicity signs and symptoms; laboratory measures of safety; and adverse and serious experiences; Immunogenicity, as judged by HIV-specific cellular responses assessed by interferon-gamma ELISpot assays and by intracellular cytokine staining (ICS)
Expected Total Enrollment:  156

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 with HIV-1 gag DNA with or without IL-12 DNA adjuvant, or with CTL multiepitope peptide (MEP) plus RC529-SE adjuvant and granulocyte-macrophage-colony stimulating factor (GM-CSF).

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 1500 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 108 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. At Months 6 and 9, Group 7 participants will receive either a placebo or CTL MEP, RC529-SE 50 adjuvant, and GM-CSF. 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.

Ages Eligible for Study:  18 Years   -   50 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

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

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 egg products or yeast-derived products

Please refer to this study by ClinicalTrials.gov identifier  NCT00111605

Study chairs or principal investigators

Spyros Kalams, MD,  Study Chair,  Vanderbilt University   

Study ID Numbers:  HVTN 060
Record last reviewed:  May 2005
Last Updated:  May 23, 2005
Record first received:  May 23, 2005
ClinicalTrials.gov Identifier:  NCT00111605
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-05-24