Safety Study of Avian Flu Vaccine
This study will determine if an experimental avian flu (bird flu) vaccine is safe, whether it has side effects and if it can stimulate an immune response in people. The vaccine being tested in this study is made from DNA (genetic material) that codes for an influenza protein called hemagglutinin 5 (H5), which is based on the protein from the bird flu virus. The study will determine if the body creates resistance or immunity to the H5 protein. The hope is that an immune response to this protein may protect against bird flu virus infection.
Healthy people between 18 and 60 years old who have been vaccinated with the current season's influenza vaccine may be eligible for this study.
Participants are randomly assigned to receive injections of one of the following: 1) study vaccine at 1 mg dose, 2) study vaccine at 4 mg dose, or 3) placebo (salt-water solution). They receive three injections about 4 weeks apart in the upper arm muscle. Participants record their temperature and symptoms at home for 5 days after each injection, either on a diary card or electronically using the Internet, and report any side effects to a study physician or nurse as soon as possible. They return to NIH for clinic visits every 2 weeks for the first 12 weeks, then at week 26 and at week 42 to check for health changes or problems. Blood is drawn at all visits and urine samples are collected through week 10.
If a participant develops serious side effects, the study physician may decide that he or she should not receive any further injections. However, all participants are asked to continue the follow-up visits even if they do not get the full set of three injections.
Influenza A Virus, H5N1 Subtype
Influenza A Virus
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Primary Purpose: Prevention
|Official Title:||VRC 304: A Phase I Study of the Safety and Immunogenicity of a Recombinant DNA Plasmid Vaccine (VRC-AVIDNA036-00-VP), Encoding for the Influenza Virus H5 Hemagglutinin Protein in Healthy Adults|
- Safety (local and systemic reactogenicity, lab tests, AEs)
- Immunogenicity (cellular and humoral immune function assays)
|Study Start Date:||December 2006|
|Estimated Study Completion Date:||August 2008|
Study Design: This is a Phase I double-blind, placebo-controlled study to evaluate safety, tolerability, and immunogenicity of a recombinant DNA vaccine against the influenza virus hemagglutinin H5. The hypothesis is that this vaccine will be safe for human administration and will elicit antibody and T cell responses against the H5 protein. The primary objectives are to evaluate the safety and tolerability of the investigational vaccine at a 1-mg and 4-mg dose in healthy adults. Secondary and exploratory objectives are related to the immunogenicity of the study vaccine.
Product Description: The vaccine is composed of a single closed-circular DNA plasmid that encodes the H5 protein with a CMV/R promoter. Vaccine vials will be supplied at 4 mg/mL. Each vaccination will be 1 mL administered intramuscularly (IM) in the deltoid muscle using the Biojector 2000 Needle-Free Injection Management System (Biojector). The placebo and diluent is phosphate buffered saline (PBS).
Subjects: A total of 45 healthy adults, ages 18-60 years, will be enrolled.
Study Plan: Subjects will be simultaneously randomized at a ratio of 1:1:1 into one of two dosage groups or a placebo group. Subjects and clinicians will be blinded to group assignment. All subjects will receive 3 injections on the schedule shown in the schema. The protocol requires nine clinic visits and three telephone follow-up contacts.
Study Duration: Each participant will complete 42 weeks of clinical follow up.
Study Endpoints: The primary endpoint is safety and tolerability of the regimen. The secondary immunogenicity endpoint is H5-specific antibody as measured by hemagglutination inhibition (HAI) assay at Study Week 12. H5-specific T cell responses measured by intracellular cytokine staining (ICS) assay, enzyme-linked immunospot (ELISPOT) assays and other immunogenicity assays at timepoints throughout the study may also be completed as exploratory evaluations.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|