VRC 307: A Double-Blind, Randomized Phase I Study of the Safety and Immunogenicity of a Prime-Boost Schedule of the Investigational DNA Trivalent Influenza Vaccine, VRC-FLUDNA047-00-VP, Followed by the 2008/2009 Seasonal Influenza Trivalent Inactivat...
- To evaluate the safety and tolerability of a prime-boost study regimen that includes the recombinant DNA vaccine followed by licensed 2008/2009 FluLaval(Registered Trademark) in adults ages 18-50 years and adults ages 51-70 years as compared with control groups that receive the licensed vaccine only.
- To evaluate whether the study participants in each age group receiving a prime-boost schedule have a greater frequency of H1 or H3 neutralizing antibodies compared with those of the same age group who received only the 2008/2009 trivalent influenza vaccine.
- To evaluate differences in antibody or T cell responses (quantity, quality, or durability) between the two groups.
- Participants ages 18 to 70 years of age who are available for clinic follow-up through Week 24 and who have no previously undiagnosed clinically significant chronic diseases. Participants will provide blood samples for further testing to determine eligibility. Females must not be or become pregnant during the study.
- Volunteers who have been immunized with the current season FDA-approved influenza vaccine (2008-2009), or who are being treated for tuberculosis may not participate.
- The study lasts for 24 weeks.
- Week 0: The first day of Week 0 (i.e., Day 0) is defined as the day of enrollment and first injection. Specific eligibility is reviewed. Participants will receive an injection of either the DNA vaccine VRC-FLUDNA047-00-VP (at 4 mg dosage) or a placebo.
- Week 4: All study participants will receive an injection of the trivalent seasonal influenza vaccine, according to the manufacturer's package insert directions.
- Participants will be given 7-day diary cards on which to record temperature and symptoms (e.g., muscle aches, headache, chills, nausea) and injection site reactions (e.g., pain, tenderness). Participants may also enter this information via the Internet. Presence of symptoms may require additional visits to the clinic.
- Participants will return to the clinic 2 weeks after each injection for the following procedures:
- Blood draws for further tests to determine the immune system's response to the vaccine(s) Clinical evaluations: vital signs and weight, examinations of the lymph nodes, and targeted physical exam on any visit if indicated by interim complaints or laboratory findings.
Drug: Flulaval (Registered) Seasonal Influenza Vaccine
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Primary Purpose: Prevention
|Official Title:||VRC 307: A D/B Randomized Ph. I Study of Safety/Immunogenicity of a Prime-Boost Schedule of an Investigational DNA Influenza Vaccine, Followed by the Seasonal Influenza Trivalent Inactivated Vaccine (TIV), Compared to TIV Alone in Healthy Adults|
- safety (local and systemic reactogenicity, lab tests, AEs)
- lmmunogenlcity (cellular and humoral immune function assays)
|Study Start Date:||March 2009|
|Study Completion Date:||June 2010|
|Primary Completion Date:||June 2010 (Final data collection date for primary outcome measure)|
This is a Phase I, randomized study in healthy younger (18-50 years) and older (51-70 years) adults. For each age group, the study will evaluate the safety, tolerability, and immunogenicity of a prime-boost vaccination regimen against the seasonal influenza virus with an investigational plasmid DNA vaccine as a prime followed 4 weeks later by the seasonal influenza trivalent inactivated vaccine (TIV) boost as compared to the seasonal TIV alone. Equal numbers of healthy adults in each age group will receive the DNA vaccine as the first injection or a control injection with phosphate buffered saline (PBS) as the first injection. The hypothesis is that the DNA vaccine will be safe for human administration and that the prime-boost schedule will elicit a higher titer antibody response than the seasonal TIV alone. The primary objectives are to evaluate the safety and tolerability and induced antibody titer of the investigational prime-boost regimen, at a dose of 4 mg for the DNA vaccine and 45 micrograms ((Micro)g) for the seasonal TIV vaccine. Secondary and exploratory objectives are related to the humoral and cellular immune responses.
The inactivated seasonal influenza vaccine is the trivalent subunit virion vaccine for the 2008-2009 season. Each dose is composed of 45 (Micro)g hemagglutinin (HA) in 0.5 mL; with the recommended ratio of 15 (Micro)g HA of each of the following 3 strains: A/Brisbane/59/2007-like (H1N1); A/Brisbane/10/2007-like (H3N2), A/Uruguay/716/2007, and B/Florida/4/2006-like. The VRC-FLUDNA047-00-VP vaccine was developed and manufactured by VRC, NIAID and is composed of 3 closed-circular DNA plasmids, each with a CMV/R promoter that encode for 2008-2009 strains of the H1, H3 and B proteins. DNA vaccine vials will be supplied at 4 mg/mL and each dose will be 1 mL. The placebo for the DNA vaccine is PBS. Vaccination will be administered intramuscularly (IM) in the deltoid muscle using needle and syringe for the seasonal influenza vaccine and the Biojector(Registered Trademark) 2000 Needle-Free Injection Management System (Biojector) for the DNA vaccine (or placebo) injection.
A total of 80 healthy adults will be enrolled; 40 in the 18-50 year age group and 40 in the 51-70 year age group.
There are two groups in the study that are based on age. Subjects in each group will be randomized into one of two vaccination schedules. Each age group is randomized at a ratio of 1:1 to either the DNA prime-TIV boost schedule or the placebo-TIV schedule. Subjects and clinicians will be blinded to assignment to DNA vaccine or placebo for first injection until all subjects have completed Study Week 8. All subjects will receive the seasonal influenza TIV vaccine as the second injection. The initial enrollments in each group will occur no faster than 4 in the first week. Before completing enrollment, there will be a study pause with review by the Protocol Safety Review Team (PSRT) when there is at least 1 week of safety follow-up on this initial group of 8 subjects' (4 in each group) first injections. Half of the subjects will have received placebo; therefore at the time of this safety review 4 injections of the investigational DNA vaccine will have been administered. A report will be provided to the Data and Safety Monitoring Board (DSMB), which will review the study twice per year.
The protocol requires 6 clinic visits and 2 telephone follow-up contacts for all groups. This study also includes a substudy of the consent process in collaboration with the NIH Clinical Center Department of Bioethics.
Group 1 (18-50 years), 40 subjects enrolled, Group 1A: n=20 and Group 1B: n=20 will received DNA IM Biojector at Day 0 and Flulaval(Registered Trademark) IM Needle at Day 28 (plus or minus 7 days)
Group 2 (51-70 years), 40 subjects enrolled, Group 1A: n=20 and Group 2B: n=20 will received DNA IM Biojector at Day 0 and Flulaval(Registered Trademark) IM Needle at Day 28 (plus or minus 7 days)
TOTAL: 80 subjects; Day 0 injection is blinded and Day 28 is open label.
Each participant will complete 24 weeks of clinical follow up.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|