HIV-1 Vaccine Test in Uninfected Adult Volunteers

Healthy Clinical Trial

Official title: Evaluation of an HIV-1 DNA Vaccine Encoding a Modified Gag-Pol Protein in Uninfected Adult Volunteers

Status Completed

Clinical Trial Summary

This study will test the safety of an experimental vaccine against HIV and will examine whether it causes an immune response to HIV virus proteins. A vaccine is given to try to create resistance or immunity to a disease or infection. The vaccine in this study is made from DNA (genetic material) of two HIV proteins called "gag" and "pol." Injected into a human, the viral DNA instructs the body to make small amounts of some HIV proteins. This study will see if the body then creates an immune response to these proteins. Study participants cannot catch HIV or AIDS from the DNA vaccine or proteins that may be made from it.

Healthy normal volunteers between 18 and 60 years of age may be eligible for this study. Candidates will provide a medical history, including information on sexual activity and drug use. They will have a physical examination, blood tests, urine test and chest X-ray. All candidates enrolled in the study must use a barrier method of contraception for sexual intercourse from the start of the study until 3 months after the last vaccination.

Participants will be assigned to one of two treatment groups: one will receive the experimental vaccine; the other will receive a control substance (inactive salt solution). The first five people assigned to the vaccine group will receive the lowest study dose of the vaccine. If this dose is safe, it will be increased three times for the next group of five and then eight times for the last group of five. Each group will have a total of seven people - five will receive the vaccine and two will get the salt solution.

Before the first injection, and possibly the second and third, a catheter (thin plastic tube) will be placed into a vein so that treatment can be given quickly if there is a reaction to the vaccine. Participants will receive three injections in an upper arm muscle-one injection a month for three months-with a needle-less device called a Biojector. For each injection, the volunteer will

• be observed for at least 1 hour after immunization

• record temperature and symptoms, including any effects at the injection site, for 2 days and report them to the clinic staff

• immediately report any side effects to a study physician or nurse.

Volunteers will have physical examinations and laboratory tests at certain times while they receive the vaccine and for a period afterwards. These procedures will require about 14 clinic visits of about 1 to 2 hours each, and up to 6 hours on vaccination days. Blood will be drawn at all visits. Some of the blood will be used for genetic tests, and some will be stored for future tests of the immune system and the body's response to the study vaccine. The study will last about 12 months from the date of the first injection. After it is completed, clinic staff may contact volunteers once or twice a year for at least 3 years to follow up.

Clinical Trial Description

This is a Phase I randomized, controlled, double-blinded dose escalation study to examine toxicity, dose and immune response of an HIV plasmid DNA vaccine. The vector used in this study has been optimized for improved safety, expression and immunogenicity. We hypothesize that this vaccine will elicit immune responses to HIV. All work will be conducted at the National Institutes of Health.

Healthy, HIV-negative volunteers will be recruited and pre-screened to confirm that they meet all of the eligibility requirements for participation. Educational materials on DNA vaccines will be reviewed with and provided to participants before enrollment into the study. There will be 3 groups of 7 volunteers. Each group will receive a constant dose of the vaccine pGag(del fs)Pol delta PR delta RT delta IN/h (5 people) or a phosphate buffered saline (PBS) control (2 people) by intramuscular inoculation. Once safety has been established, successive groups will receive a higher dose. Study groups will receive three immunizations containing either 0.5 mg (Group 1), 1.5 mg (Group 2), or 4.0 mg (Group 3) of a DNA vaccine. Dose escalation will be initiated 5 weeks after the last volunteer in the previous dose group receives their first inoculation, providing there are no significant toxicities.

Vaccine-related adverse reactions will be evaluated at scheduled study visits and by study participant report. Immune response will be evaluated as described in Appendix II. Specimens to evaluate immunogenicity will be taken at baseline, and at the time points indicated in Appendix VIII. Unless contraindicated, subsequent inoculations using repeat plasmid vaccinations will be given 28 and 56 days after the first vaccinations. The estimated duration for each volunteer to complete immunizations and follow-up is 12 months. ;

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy
• HIV Seronegativity

• NCT number: NCT00009685
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: January 2001
• Completion date: March 2005