The purpose of the study is to determine the safety of and immune response to an investigational HIV vaccine, VRC-HIVDNA016-00-VP, and a vaccine booster, VRC-HIVADV014-00-VP, in HIV uninfected adults from Kenya, Tanzania, and Uganda.

Condition	Intervention	Phase
HIV Infections	Vaccine: VRC-HIVDNA016-00-VP  Vaccine: VRC-HIVADV014-00-VP	Phase I Phase II

Further Study Details: 

Primary Outcomes: Local reactogenicity signs and symptoms; systemic reactogenicity signs and symptoms; laboratory measures of safety; adverse and serious adverse experiences; unfractionated IFN-gamma ELISPOT responses to HIV-1 at Day 196; CD4+ and CD8+ T cell responses to HIV-1, as measured by flow cytometry-based intracellular cytokine staining (ICS) assay at Day 196
Expected Total Enrollment:  324

The worldwide HIV/AIDS epidemic may only be controlled through development of a safe and effective vaccine that will prevent HIV infection. This study will evaluate the safety and immunogenicity of an experimental adenovirus-vectored multiclade HIV vaccine, VRC-HIVADV014-00-VP, followed with or without a similarly structured DNA plasmid HIV vaccine, VRC-HIVDNA016-00-VP. The DNA in both vaccines code for proteins from HIV subtypes A, B, and C, which together represent 90% of new HIV infections in the world. HIV uninfected volunteers will be recruited in the East African nations of Kenya, Tanzania, and Uganda.

This study will comprise two parts, A and B. Part A will enroll 144 participants who will be randomly assigned to one of four different groups:

• Group 1 participants will receive a low dose of the adenovirus-vectored HIV vaccine or placebo at study entry.
• Group 2 participants will receive a higher dose of the adenovirus-vectored HIV vaccine or placebo at study entry.
• Group 3 will receive the DNA plasmid vaccine or placebo at study entry and Days 28 and 56. They will also receive either a low dose of the adenovirus-vectored HIV vaccine or placebo at Day 168.
• Group 4 will receive the DNA plasmid vaccine or placebo at study entry and Days 28 and 56. They will also receive either a higher dose of the adenovirus-vectored HIV vaccine or placebo at Day 168.

Enrollment into Part B (Group 5) will begin after the completion of the safety data evaluation of Groups 3 and 4 and after Part A has been fully enrolled. Group 5 participants will receive the DNA plasmid vaccine or placebo at study entry and Days 28 and 56. They will also receive either a low dose of the adenovirus-vectored HIV vaccine or placebo at Day 168.

There will be 11 study visits over 14 to 16 months for Groups 1 and 2. All study visits will include a physical exam, medical and medication history, vital signs measurement, lymph node assessment, HIV and pregnancy counseling, and blood and urine collection. A home visit will also occur at study entry. A 3-day diary card to report side effects will be completed by participants at study entry and on Days 28, 56, 168, and 210.

There will be 14 study visits for Groups 3, 4, and 5; these visits will include the same tests and assessments as for Groups 1 and 2.

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

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• Good general health
• Willing to follow all the requirements of the study and available for follow-up for the duration of the study (14 to 16 months)
• Able and willing to provide informed consent
• Willing to undergo HIV testing and counseling and willing to receive HIV test results
• Willing to not engage in high-risk behavior for HIV infection during the study
• Willing to provide location and be visited at home
• Willing to be identified with picture identification for study purposes
• Willing to use acceptable forms of contraception

Exclusion Criteria:

• HIV or HBV infection
• HIV vaccines in prior HIV vaccine trial
• Immunosuppressive or cytotoxic medications within the 6 months prior to study entry. Participants who have used corticosteroid nasal spray for allergic rhinitis or topical corticosteroids for acute uncomplicated dermatitis are not excluded.
• Blood products within 120 days prior to study entry
• Immunoglobulin within 60 days prior to study entry
• Live attenuated vaccines within 30 days prior to first study vaccine administration
• Medically indicated subunit or killed vaccines or allergy treatment with antigen injections within 14 days prior to first study vaccine administration
• Investigational research agents within 30 days prior to first study vaccine administration
• Current tuberculosis prophylaxis or therapy
• Participated in high-risk behavior for HIV infection within 6 months prior to study entry. More information on this criterion can be found in the protocol.
• Serious adverse reactions to vaccines, such as anaphylaxis, hives, respiratory difficulty, angioedema, or abdominal pain
• Autoimmune disease or immunodeficiency
• Unstable asthma or asthma requiring emergent or urgent care, hospitalization, intubation, or oral or intravenous corticosteroids during the 2 years prior to study entry
• Diabetes mellitus type 1 or 2. Patients with gestational diabetes are not excluded.
• Thyroid disease, including removal of thyroid or disease requiring medication within 3 years prior to study entry
• Serious angioedema within 3 years prior to study entry or disease requiring medication within 2 years prior to study entry
• Uncontrolled hypertension
• Bleeding disorder
• Active syphilis
• Active cancer OR treated cancer that may recur during the duration of the study
• Seizure disorder. Participants who have had fever-related seizures prior to age 2 are not excluded.
• Absence of spleen OR partial or complete lack of splenic function
• Psychiatric condition that may interfere with the study, including past or present psychoses, bipolar disorder, or suicidal attempts
• Any medical, psychiatric, or social condition that, in the opinion of the investigator, may interfere with the study
• Any occupational or other responsibility that, in the opinion of the investigator, may interfere with the study
• Pregnancy, breastfeeding, or plan to become pregnant

Please refer to this study by ClinicalTrials.gov identifier  NCT00123968

Study chairs or principal investigators

Merlin Robb, MD,  Study Chair,  U.S. Military HIV Research Program   

Study ID Numbers:  RV 172
Record last reviewed:  July 2005
Last Updated:  July 25, 2005
Record first received:  July 25, 2005
ClinicalTrials.gov Identifier:  NCT00123968
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-07-26