Safety and Immune Response to a Recombinant Adenovirus HIV-1 Vaccine in Healthy Adults

A Phase I Randomized, Double-blind, Placebo Controlled Dose Escalation Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant Adenovirus Serotype 5 HVR48 HIV-1 Vaccine (Ad5HVR48.ENVA.01) in Healthy, HIV-1 Uninfected Adults (Ad5HVR48.ENVA.01 (rAd5HVR48) HIV-1/IPCAVD-002 Vaccine Study)

Successful control of the HIV epidemic will require a safe and effective vaccine to be developed. A successful vaccine will need to stimulate a widespread immune response. The purpose of this study is to determine the safety of and immune response to an adenovirus serotype HIV vaccine in HIV uninfected adults.

Control of the HIV pandemic can only be achieved with the development of a safe and effective preventive HIV vaccine. A vaccine that will prevent HIV infection will elicit a strong immune response from both CD4 and CD8 cells. Recombinant adenovirus serotype vectors have been shown to elicit just such a response. The purpose of this study is to determine the safety and immunogenicity of the recombinant adenovirus serotype 5 preventive HIV-1 vaccine.

This study will last 18 to 24 months. Participants will be randomly assigned to one of four arms that will receive vaccine or placebo administered via intramuscular injection. Participants in Arms 1, 2, and 3 will all receive 3 injections. Participants in Arm 4 will receive one injection. For most participants, there will be 10 study visits in this study; for participants in Arm 4, there will be only 7 visits. For Arms 1, 2, and 3, study visits will occur at baseline and on Days 0, 14, 28, 42, 56, 168, 182,196, and 365. Participants in Arms 1, 2, and 3 will receive injections on Days 0, 28, and 168. For participants in Arm 4, study visits will occur at baseline and on Days 0, 14, 28, 56, 168 and 365. Participants in Arm 4 will receive one injection only, on Day 0. Participants will be asked to record their temperature and other side effects in a symptom log for 3 days after each injection. Risk reduction/pregnancy prevention counseling and physical exams will occur at all visits. At most visits, blood, urine, and oral swab collection will occur. Samples collected will be stored for future testing. HIV testing and pregnancy testing will occur at select visits. At Years 2, 3, 4, and 5, participants will be followed-up by telephone, e-mail, or study visit to collect vital status, and information about any development of significant disability or incapacity, hospitalizations, or congenital anomalies. At these follow-up visits, blood collection will be optional.

Inclusion Criteria:

• Good general health
• Normal hematological, hepatic and renal functions
• Demonstrated understanding of study
• Willing to receive HIV test results
• HIV-1 and -2 uninfected
• Hepatitis B surface antigen negative
• Anti-hepatitis C virus (anti-HCV) negative antibody or negative HCV PCR if anti-HCV is positive
• Adequate contraception. For more information on this criterion can be found in the protocol.

Exclusion Criteria:

• HIV vaccines or placebos in prior HIV vaccine trial
• Immunosuppressive medications within 168 days prior to first injection. Participants taking corticosteroid nasal spray or topical corticosteroids are not excluded.
• Blood products within 120 days prior to first injection
• Immunoglobulin within 60 days prior to first injection
• Investigational agents within 30 days prior to first injections
• Live attenuated vaccine within 30 days prior to first injection
• Any vaccine that is not a live attenuated vaccine within 14 days prior to first injection
• Any clinically significant medical condition that, in the opinion of the investigator, may interfere with the study
• Any medical, psychiatric, occupational, or social condition or responsibility that, in the opinion of the investigator, would interfere with the study
• Serious adverse reaction to vaccines. Participants who had a nonanaphylactic adverse reaction to pertussis vaccine as a child are not excluded.
• Known autoimmune disease
• Known immunodeficiency
• Asthma other than mild, well-controlled asthma
• Diabetes mellitus type 1 or 2
• Thyroidectomy or thyroid disease in the12 months prior to study entry
• Angioedema in the 3 years prior to study entry
• Hypertension. More information on this criterion can be found in the protocol.
• Body mass index (BMI) of 40 or higher OR BMI of 35 or greater, if other cardiovascular risk factors. More information on this criterion can be found in the protocol.
• 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 or occurrence of seizure in the 3 years prior to study entry. Participants who have not required medications or had a seizure for prior 3 years are not excluded.
• Absence of spleen
• Individuals at high-risk of acquiring HIV infection
• Presence of pre-existing neutralizing antibodies for Adenovirus 5 or 48
• Pregnancy or breastfeeding