Safety and Immunogenicity Study of an Inactivated H5N1 Influenza Vaccine (Whole Virion, Vero Cell Derived)

A Phase I/II Dose Escalation Study of a Vero Cell-Derived, Whole Virus H5N1 Influenza Vaccine in Healthy Volunteers Aged 18 to 45 Years

The objective of this study is to assess the safety and immunogenicity of 4 different doses of adjuvanted and non-adjuvanted mock-up pandemic influenza vaccine. Subjects will be enrolled sequentially into 3 study cohorts with 4 escalating doses of H5N1 hemagglutininin antigen (3.75 µg adjuvanted, 7.5 µg adjuvanted/non-adjuvanted, 15 µg adjuvanted/non-adjuvanted, 30 µg adjuvanted). Starting with the lowest dose level, subjects will receive 2 vaccinations (21 days apart) at the dose to which they were assigned. Subjects will be monitored for safety and for antibody response to the vaccine. A data safety monitoring board will review and evaluate all the safety data obtained for a dose level before allowing administration of the next (higher) dose.

Inclusion Criteria:

Male and femal subjects who

• are 18 to 45 years of age, inclusive, on the day of screening;
• have an understanding of the study, agree to its provisions, and give written informed consent prior to study entry;
• are clinically healthy, as determined by medical history and physical examination;
• agree to keep a daily record of symptoms;
• if female and capable of bearing children, have a negative urine pregnancy test result at study entry and agree to employ adequate birth control measures for the duration of the study.

Exclusion Criteria:

Subjects who

• are at high risk of contracting H5N1 influenza infection (e.g. poultry workers);
• suffer from a significant neurological, cardiac, pulmonary (including asthma), hepatic, rheumatic, autoimmune, hematological or renal disorder;
• are unable to lead an independent life as a result of either physical or mental handicap;
• suffer from any kind of immunodeficiency;
• suffer from a disease or are undergoing a form of treatment 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 a history of inflammatory or degenerative neurological disease (e.g. Guillain Barré);
• have a history of severe allergic reactions or anaphylaxis;
• have a rash, dermatologic condition or tattoos which may interfere with injection site reaction rating;
• have received a blood transfusion or immunoglobulins within 90 days of study entry;
• have donated blood or plasma within 30 days of study entry;
• have received any live vaccine within 4 weeks or inactivated vaccine within 2 weeks prior to vaccination in this study;
• have undergone systemic corticoid therapy within 30 days prior to study entry;
• have a functional or surgical asplenia;
• have a known or suspected problem with alcohol or drug abuse;
• were administered an investigational drug within six 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 the study investigator. Dependent relationships include close relatives (i.e., children, partner/spouse, siblings, parents) as well as employees of the investigator;
• if female, are pregnant or lactating.