Open-Label, Randomized Phase 1b Study of the Safety & Immunogenicity of Investigational Seasonal Influenza DNA Vaccine Followed by TIV Administered Intradermally (ID) or Intramuscularly (IM) in Healthy Adults 18-70 Years
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Influenza
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 316
- Locations
- 4
- Primary Endpoint
- Incidence of unsolicited adverse events of any severity for 28 days after the second injection
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a Phase Ib study in healthy adults (18-70 years) to evaluate the safety, tolerability, and immunogenicity of same season and sequential season vaccination schedules consisting of the 2012/2013 seasonal influenza DNA vaccine (HA DNA) and licensed trivalent influenza vaccine (TIV) administered intradermally (ID) or intramuscularly (IM). The hypothesis is that evaluation of these investigational schedules will inform development of novel influenza vaccine strategies that may offer improved and cross-protective immunity against antigenically diverse influenza strains.
Detailed Description
Vaccines are an effective way to prevent influenza infection. Each year the World Health Organization (WHO) and the U.S FDA recommend the influenza strains to include in the seasonal influenza vaccines. The licensed seasonal influenza vaccines are directed against 3 influenza virus strains: an influenza A H1N1, an influenza A H3N2, and an influenza B. The currently approved vaccines depend upon labor-intensive methods that limit manufacturing speed and capacity. Influenza vaccines that can be more rapidly produced and that induce stronger, broader and more persistent immune responses are a recognized public health need. In this protocol we propose to use DNA vaccine antigen delivery to induce immune responses against native hemagglutinin (HA) structures prior to boosting with licensed TIV ID or with TIV IM. The study will allow evaluation of the safety and immunogenicity of same season and sequential season vaccination schedules. The same season regimens (2012/13 prime and boost with a 14 week interval) consist of HA DNA prime with TIV ID boost -- or -- HA DNA prime with TIV IM boost. The active comparator for these schedules are TIV ID or TIV IM alone because a single dose of TIV is the standard for adult influenza vaccination within a single season. The sequential season regimens (2012/13 prime and 2013/14 boost) consist of concurrent administration (in different arms) of HA DNA and TIV ID prime with TIV ID boost -- or -- HA DNA and TIV IM prime with TIV IM boost. The active comparator for these regimens will be TIV ID followed by TIV ID boost -- or -- TIV IM followed by TIV IM boost, administered sequential seasons consistent with as typical pattern of use for these licensed vaccines. Evaluation of the investigational schedules and active comparator schedules will inform development of novel influenza vaccine strategies that may offer improved and cross-protective immunity against diverse influenza strains.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A subject must meet all of the following criteria:
- •Healthy adults, 18 to 70 years old; volunteers who will be older than 64 during the 2013/2014 influenza season will not be enrolled after 11/16/
- •Available for clinical follow-up
- •Able and willing to complete the informed consent process
- •Willing to donate blood for sample storage to be used for future research
- •Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) ≤40 within the 70 days prior to enrollment
- •Has not yet received the current year (2012/13) influenza vaccine prior to enrollment and agrees to receive seasonal influenza vaccines during study participation only from the study site
- •Laboratory Criteria within 70 days prior to enrollment:
- •Hemoglobin within institutional normal limits
- •White blood cells either within institutional normal range or accompanied by site physician approval as consistent with healthy adult status
Exclusion Criteria
- •A subject will be excluded if one or more of the following conditions apply:
- •Women Specific:
- •Breast-feeding or planning to become pregnant while participating in the study
- •Subject has received any of the following substances:
- •More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 12 weeks prior to enrollment or any within the 14 days prior to enrollment
- •Blood products within 16 weeks prior to enrollment
- •Immunoglobulin within 8 weeks prior to enrollment
- •Investigational research agents within 28 days (4 weeks) prior to enrollment or planning to receive investigational products while on the study.
- •Allergy treatment with antigen injections, unless on maintenance schedule and allergy shots could be staggered with the study vaccinations, within 14 days (2 weeks) prior to enrollment
- •Current anti-tuberculosis (TB) prophylaxis or therapy
Outcomes
Primary Outcomes
Incidence of unsolicited adverse events of any severity for 28 days after the second injection
Time Frame: Day of injection to 28 days after injection
The 28 day period following second injection is defined by the actual day of second injection.
Geometric Mean HAI Titer for each of the 2012/13 influenza vaccine strains (Group 1 and Group 2)
Time Frame: Day 119
Blood is collected 3 weeks following completion of the 2012/2013 vaccination regimen 3 weeks after 2012/13 TIV ID or TIV IM boost for (Group 1 and Group 2, Day 119) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Incidence of solicited adverse events after the second injection
Time Frame: Day of injection to 7 days after second injection
Incidence is reported for solicited events for 7 days after the second injection. The period of solicitation is defined by the actual day of second injection.
Incidence of unsolicited adverse events of any severity 28 days after the first injection
Time Frame: Day 0 to Day 28
Incidence is reported for unsolicited events for 28 days after the first injection. For all Groups the reporting period for unsolicited adverse events following the first injection Day 0 to Day 28.
Proportion of subjects with seroconversion for each of the 2012/13 influenza vaccine strains (Group 1 and Group 2)
Time Frame: Day 119
Seroconversion is defined a pre-vaccination strain-specific HAI titer \<1:10 and a post-vaccination hemagglutination inhibition (HAI) titer ≥1:40 or a pre-vaccination. Blood is collected at baseline (Day 0) and at 3 weeks following completion of the 2012/2013 vaccination regimen (3 weeks after 2012/13 TIV ID or TIV IM boost for Group 1 and Group 2, Day 119) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Geometric Mean HAI titer for each of the 2012/13 influenza vaccine strains (Group 3 and Group 4)
Time Frame: 3 weeks after completion of the HA DNA prime, Day 21
Blood is collected 3 weeks following completion of the 2012/2013 prime injection (3 weeks after 2012/13 TIV ID or TIV IM prime Group 3 and Group 4, Day 21) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Incidence of solicited adverse events after the first injection
Time Frame: Day 0 to Day 7
Incidence is reported for solicited events for 7 days after the first injection. For all Groups the collection period for solicited adverse events following the first injection Day 0 to Day 7.
Proportion of subjects with seroconversion for each of the 2012/13 influenza vaccine strains (Group 3 and Group 4)
Time Frame: Day 21
Blood is collected at baseline (Day 0) and at 3 weeks following completion of the 2012/2013 prime injection (3 weeks after 2012/13 TIV ID or TIV IM prime Group 3 and Group 4, Day 21) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Incidence of serious adverse events or new chronic medical conditions through 24 weeks after the 2nd injection
Time Frame: Day 0 to 24 weeks after second injection
The day of second injection varies by group; the duration of time from Day 0 through 24 weeks after second injection is defined by the actual day of second injection.
Number of subjects with influenza or influenza-like illnesses (ILI)
Time Frame: Day 0 to 24 weeks after second injection
The day of second injection varies by group; the duration of time from Day 0 through 24 weeks after second injection is defined by the actual day of second injection.
Mean change from baseline in safety laboratory measures
Time Frame: Day 21
At Day 21 (window Day 21-28) blood will be drawn to measure hemoglobin, hematocrit, red blood cells (RBC), white blood cells (WBC), mean corpuscular volume (MCV), platelets
Secondary Outcomes
- Seroconversion for each of the 2012/13 and 2013/14 influenza vaccine strains(3 weeks after each study injection)
- Geometric Mean neutralization titer of 2012/13 and 2013/14 influenza vaccine strain-specific H1, H3, and B neutralizing antibodies(3 weeks after each study injection)
- Geometric Mean HAI Titer for each of the 2012/13 and 2013/14 influenza vaccine strains(3 weeks after each study injection)
- Proportion of subjects with four-fold rise from baseline for each of the 2012/13 and 2013/14 influenza vaccine strain-specific H1, H3, and B neutralizing antibodies(3 weeks after each study injection)