E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
H5N1 vaccination in healthy subjects (adult and elderly population) and in specified risk groups (chronically ill, transplant and HIV patients). |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059430 |
E.1.2 | Term | Influenza immunization |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To assess the safety and tolerablilty of a non-adjuvanted H5N1 influenza vaccine in an adult and elderly population and in specified risk groups;
- To assess the immune response to a non-adjuvanted H5N1 influenza vaccine in an adult and elderly population and in specified risk groups;
- To demonstrate consistency of immune response among three diferent lots of a non-adjuvanted H5N1 influenza vaccine.
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E.2.2 | Secondary objectives of the trial |
- To assess persistence of H5N1 influenza antibodies after vaccination with a non-adjuvanted H5N1 influenza vaccine in an adult and elderly population and in specified risk groups;
For a subset of subjects included in the evaluation of cellular immunity a further objective of the study is: -To evaluate the T-cell mediated immune response induced by an H5N1 influenza after the first and second vaccinations. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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, as determined by the investigator's clinical judgment through collections of medical history and performance of a physical examination.
The following inclusion criterion applies to subjects in Cohort 2 only: - Are immune compromised due to immunosuppressive treatment (e.g. transplant patients) or due to acquired immunodeficiency caused by HIV infection with or without treatment with anti-retrovirals
The following inclusion criterion applies to subjects in Cohort 3 only: - Have a chronic cardiovascular (excluding hypertension, respiratory, renal, or metabolic (diabetes mellitus) illness in stable clinical condition without major disease complications such as organ failure, infectious complications, severe asthma or respiratory dysfunction. |
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E.4 | Principal exclusion criteria |
The following exclusion criteria apply to sujects in all three cohorts: - Have a history of exposure to H5N1 virus or a history of vaccination with an H5N1 influenza virus; - Are at high risk of contracting H5N1 influenza infection (e.g. poultry workers); - Have a history of severe allergic reactions or anaphylaxis; - Have a rash, dermatological condition or tattoos which may interfere with injection site reation rating; - Have donated blood or plasma within 30 days prior to study entry; - Have received any live vaccine within 4 weeks or inactivated vaccine within 2 weeks prior to vaccination in this study; - Have a known or suspected problem with alcohol or drug abuse; - Were administered an investigational drug within 6 weeks prior to study entry or are concurrently participating in a clinical study that includes the administration of an investigational product; - Are a member of the team conducting this study or are in a dependent relationship with one of the study team members. - If female: are pregnant or lactating.
The following exclusion criteria apply to subjects in Cohort 1 only: - Currently have or have a history of a significant neurological, cardiovascular, pulmonary (including asthma), hepatic, meatbolic, rheumatic, autoimmune, hematological or renal disorder*; - Have any inherited or acquired immunodeficiency; - Have a disease or are currently undergoing a form of treatment or were undergoing a form of treatment within 30 days prior to study entry that can be expected to influence immune response. Such treatment includes, but is not limited to, systemic or high dose inhaled (>800µg/day of beclomethasone dipropionate or equivalent) corticosteroids, radiation treatment or other immunosuppressive or cytotoxic drugs; - Have received a blood transfusion or immunoglobulins within 90 days prior to study entry; - Have a functional or surgcial asplenia.
*A significant disorder is defined as a disease or medical condition associated with impaired health status, increased risk for complications, requiring medical treatment and/or follow up.
The following exclusion criterion applies to subjects in Cohort 2 only: - Are immune compromised due to stem cell or organ-transplantation with significant medical complications such as acute or chronic graft rejection or graft versus host disease requiring intensive immunosuppressant treatment, transplant failure, or infectious complications or other conditions that would be considered a contraindication for vaccination with an inactivated vaccine. - Are immune compromised due to HIV infection and have a CD4 count of <200x10 6/L at screening or significant medical complications such as oppotunistic infections, malignant complications (e.g. lymphoma, Kaposi sarcoma), other organ manifestations consistent with advanced acquired immunodeficiency syndromme (AIDS) or other conditions that would be considered a contraindication for vaccination with an inactivated vaccine.
The following exclusion criterion applies to subjects in Cohort 3 only: -Have a chronic cardiovascular, respiratory, renal, or metabolic (e.g.diabetes meelitus) illness with significant complications such as advanced heart failure, liver failure, renal failure, severe asthma or severe respiratory failure, infectious complications or other conditions that would be considered a contraindication for vaccination with an inactivated vaccine. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Safety Endpoints: - Frequency and severity of systemic reactions after the first and second vaccinations.
Primary Immunogenicity Endpoints: - Antibody response 21 days after the second vaccination as measured by Microneutralization (MN) assay. • Number of subjects with antibody response to the vaccine strain (A/Vietnam/1203/2004) associated with protection 21 days after the second vaccination defined as titer measured by MN assay ≥ 1:20.
Secondary Safety Endpoints • Frequency and severity of injection site reactions until 21 days after the first and second vaccinations; • Number of subjects with fever, malaise or shivering with onset within 7 days after the first and second vaccinations; • Frequency and severity of adverse events (AEs) observed during the entire study period.
Secondary Immunogenicity Endpoints • 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; • 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; • 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; • Antibody response 21 days after the first vaccination as measured by MN assay; • Antibody response 21 days after the first and second vaccinations as measured by HI and SRH assays; • 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; • Number of subjects demonstrating seroconversion (defined as a minimum four fold titer increase as compared to baseline [for MN and HI assays] or as either a ≥ 25 mm2 hemolysis area after the vaccination in case of a negative prevaccination sample [≤ 4 mm2] or a ≥ 50% increase in hemolysis area if the pre-vaccination sample is > 4 mm2 [for SRH assay]) 21 days after the first and second vaccinations as measured by MN, HI and SRH assays; • Number of subjects with antibody response associated with protection 201 days after the first vaccination as measured by MN, HI and SRH assays; • Antibody response 201 days after the first vaccination as measured by MN, HI and SRH assays; • Fold increase of antibody response 201 days after the first vaccination as compared to baseline as measured by MN, HI and SRH assays.
Additional secondary immunogenicity endpoints for the subset of subjects included in the assessment of antibody kinetics: • Number of subjects with antibody response associated with protection 28, 35 and 90 days after the first vaccination as measured by MN, HI and SRH assays; • Antibody response 28, 35 and 90 days after the first vaccination as measured by MN, HI and SRH assays; • Fold increase of antibody response 28, 35 and 90 days after the first vaccination as compared to baseline as measured by MN, HI and SRH assays; • Number of subjects demonstrating seroconversion (defined as a minimum four fold titer increase as compared to baseline [for MN and HI assay] or as either a ≥ 25 mm2 hemolysis area after the vaccination in case of a negative prevaccination sample [≤ 4 mm2] or a ≥ 50% increase in hemolysis area if the pre-vaccination sample is > 4 mm2 [for SRH assay]) 28, 35 and 90 days after the first vaccination as measured by MN, HI and SRH assays.
Additional secondary endpoints for the subset of subjects included in the evaluation of cellular immunity: • T-cell response after each vaccination as determined by the frequency of cytokine producing T-cells induced by influenza virus antigens; • Increase in frequency of cytokine producing T-cells induced by influenza virus antigens after each vaccination as compared to baseline. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
3.75 microgram Vietnam strain |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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This study is terminated when the last subject completes day 201. The study may be prematurely terminated if SAE or other significant vaccine related side effects occur. In addition the sponsor may stop the entire study for any medical reason at any time. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |