Phase 3 Study of a H5N1 Vaccine in Adults, Elderly and Specified Risk Groups

An Open-Label Phase 3 Study to Assess the Safety and Immunogenicity of a Vero Cell-Derived Whole Virus H5N1 Influenza Vaccine in an Adult and Elderly Population as Well as in Specified Risk Groups

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.

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 exclusion criteria apply to subjects in all three cohorts:

Subjects will be excluded from participation in this study if they:

• Have a history of exposure to H5N1 virus or a history of vaccination with an H5N1 influenza vaccine;
• 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 reaction 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. Dependent relationships include close relatives (i.e., children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study;
• 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, metabolic, rheumatic, autoimmune, hematological or renal disorder [4];
• 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 surgical asplenia.

([4]) 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 criteria apply 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 immunosuppressive 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 with a CD4 count of < 200x10^6/L at screening or significant medical complications such as opportunistic infections, malignant complications (e.g. lymphoma, Kaposi sarcoma), other organ manifestations consistent with advanced acquired immunodeficiency syndrome (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 mellitus) 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.