Influenza
Conditions
Keywords
Influenza (Pandemic)
Brief summary
The purpose of this study is to assess the safety and tolerability of, and the immune response to a non-adjuvanted H5N1 influenza vaccine in an adult and elderly population and in specified risk groups. Furthermore, persistence of H5N1 influenza antibodies after vaccination with this vaccine will be assessed.
Interventions
BIOLOGICALH5N1 Influenza Vaccine Whole virion, Vero cell-derived, Inactivated Influenza Vaccine, non-adjuvanted
Intramuscular injection of 7.5 µg hemagglutinin antigen (A/Vietnam/1203/2004 strain) in a non-adjuvanted formulation on Days 0 and 21.
Sponsors
Alachua Government Services, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
The following inclusion criteria apply to subjects in all three cohorts: Male and female subjects will be eligible for participation in this study if they: * Are 18 years of age or older on the day of screening; * Have an understanding of the study and its procedures, agree to its provisions, and give written informed consent prior to study entry; * Are physically and mentally capable of participating in the study and follow its procedures; * Agree to keep a daily record of symptoms for the duration of the study; * If female of childbearing potential - have a negative urine pregnancy test result within 24 hours prior to the scheduled first vaccination and agree to employ adequate birth control measures for the duration of the study. The following inclusion criterion applies to subjects in Cohort 1 only: \- Are generally healthy \[1\], as determined by the investigator's clinical judgment through collection of medical history and performance of a physical examination. (\[1\]) Subjects with controlled Stage 1 hypertension (blood pressure of 140-159 mmHg systolic and/or 90-99 mmHg diastolic) are eligible for participation in Cohort 1 of this study. The following inclusion criterion applies to subjects in Cohort 2 only: \- Are immune compromised due to immunosuppressive treatment (e.g. transplant patients \[2\]) or due to acquired immunodeficiency caused by HIV infection with or without treatment with anti-retrovirals. (\[2\]) Transplant patients should be at least 6 months after transplantation and in stable clinical condition without complications. The following inclusion criterion applies to subjects in Cohort 3 only: \- Have a chronic cardiovascular (excluding hypertension) \[3\], respiratory, renal, or metabolic (e.g. diabetes mellitus) illness in stable clinical condition without major disease complications such as organ failure, infectious complications, severe asthma or respiratory dysfunction. (\[3\]) Subjects with cardiovascular disease such as coronary heart disease, angina, heart attack or other heart conditions in stable clinical condition, without major disease complications and who are considered at risk for medical complications from influenza. However, subjects with hypertension (see \[1\] above) not associated with any heart condition will be excluded from participation in Cohort 3 of this study.
Exclusion criteria
The following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency and severity of systemic reactions until 21 days after the first and second vaccinations | 42 days |
| Number of subjects with antibody response to the vaccine strain associated with protection 21 days after the second vaccination defined as titer measured by microneutralization (MN) assay >= 1:20. | 42 days |
| Antibody response 21 days after the second vaccination as measured by MN assay; | 42 days |
Secondary
| Measure | Time frame |
|---|---|
| Frequency and severity of adverse events observed during the entire study period | 11 months |
| Number of subjects with antibody response associated with protection 21 days after the first and second vaccinations defined as Hemagglutination Inhibition Antibody (HIA) titer >= 1:40 or Single Radial Hemolysis (SRH) area >= 25 mm2 | 42 days |
| Number of subjects with antibody response associated with protection 21 days after the second vaccination defined as titer measured by MN assay >=1:40, >= 1:80, >=1:160 | 42 days |
| Antibody response 21 days after the first and second vaccinations as measured by HI and SRH assays | 42 days |
| Fold increase of antibody response 21 days after the first and second vaccinations as compared to baseline as measured by MN, HI and SRH assays | 42 days |
| Number of subjects with seroconversion (MN/HI: min.4-fold titer increase vs baseline;SRH:post-vacc. hemolysis area >=25mm2 or increased by >=50% for pre-vacc. sample <=4mm2 and >4mm2, resp., 21 days after 1st and 2nd vaccinations, measured by MN,HI,SRH | 42 days |
| Number of subjects with antibody response associated with protection 201 days after the first vaccination as measured by MN, HI and SRH assays | 201 days |
| Antibody response 201 days after the first vaccination as measured by MN, HI and SRH assays | 201 days |
| Antibody response in the subset of subjects included in the assessment of antibody kinetics 28, 35 and 90 days after the first vaccination as measured by MN, HI and SRH assays | 90 days |
| Number of subjects in the subset included in the assessment of antibody kinetics with antibody response associated with protection 28, 35 and 90 days after the first vaccination as measured by MN, HI and SRH assays | 90 days |
| Fold increase of antibody response in the subset of subjects included in the assessment of antibody kinetics 28, 35 and 90 days after the first vaccination as compared to baseline as measured by MN, HI and SRH assays | 90 days |
| Number of subjects in subset for antibody kinetics evaluation with seroconversion (see definitions above) 28, 35, 90 days after 1st vaccination, measured by MN, HI, SRH | 90 days |
| T-cell response in the subset of subjects included in the evaluation of cellular immunity after each vaccination as determined by the frequency of cytokine producing T-cells induced by influenza virus antigens | 201 days |
| Increase in frequency of cytokine producing T-cells induced by influenza virus antigens after each vaccination as compared to baseline | 201 days |
| Number of subjects with antibody response associated with protection 21 days after the first vaccination defined as titer measured by MN assay >=1:20, >=1:40, >=1:80, >=1:160 | 21 days |
| Antibody response 21 days after the first vaccination as measured by MN assay | 21 days |
| Fold increase of antibody response 201 days after the first vaccination as compared to baseline as measured by MN, HI and SRH assays | 201 days |
| Frequency and severity of injection site reactions until 21 days after the first and second vaccinations | 42 days |
| Number of subjects with fever, malaise or shivering with onset within 7 days after the first and second vaccinations | 7 days |
Countries
Austria, Belgium, Finland, Germany, Latvia, Lithuania, Netherlands
Outcome results
None listed