Immunogenicity and Safety of Influenza Virus Vaccine, AdimFlu-S (A/H1N1), in Pediatric Population

• The primary immunogenicity objective is to assess the antibody response following a single dose of study vaccine, grouped by age of recipient, when administered at the 7.5 or 15 μg HA doses. [ Designated as safety issue: No ]
• The primary safety objective of this study is to assess the safety of the study vaccine when administered at the 7.5 or 15 μg HA doses. [ Designated as safety issue: Yes ]

This is a laboratory-blinded study in healthy toddlers, children, and teenagers designed to investigate the safety, reactogenicity, and immunogenicity of an inactivated influenza H1N1 vaccine (AdimFlu-S). There are 3 age strata, and each contains at least 50 subjects: greater than or equal to 1 year to less than 3 years, greater than or equal to 3 years to less than 6 years, and greater than or equal to 6 years to less than 18 years. In each age strata, all eligible subjects received 2 injections of AdimFlu-S (A/H1N1) at a designated dosage level (7.5 μg, 15 μg and 15 μg for 1~<3, 3~<6 and 6~<18 years, respectively) at 3 weeks apart.

Following immunization, safety is measured by assessment of adverse events for 6 weeks following the first vaccination, serious adverse events and new-onset chronic medical conditions through 7 months post first vaccination, and reactogenicity to the vaccines for 7 days following each vaccination. Immunogenicity testing includes hemagglutination inhibition (HAI) testing on serum obtained before first vaccination, and three and six weeks after first vaccination.

• Experimental: H1N1 vaccine of 15 μg HA on Day 0 and 21
  15 μg HA (0.5 mL) per injection, 2 injections 50 children (aged over 3 years old to 6 years old) and 50 children/teenagers (aged over 6 years old to 18 years old) were assigned to receive two injections of H1N1 vaccine 3 weeks apart
  Intervention: Biological: Influenza A (H1N1) 2009 monovalent vaccine, inactivated
• Experimental: H1N1 vaccine of 7.5 μg HA on Day 0 and 21
  7.5 μg HA (0.25 mL) per injection, 2 injections 50 toddlers (aged over 1 year old to 3 years old) were assigned to receive two injections of H1N1 vaccine 3 weeks apart
  Intervention: Biological: Influenza A (H1N1) 2009 monovalent vaccine, inactivated

Inclusion Criteria:

• Boys or girls aged ≧ 1 year old to 18 years old on the day of first vaccination;
• Subject and/or parents(s)/legal guardian(s) was willing to comply with planned study procedures and be available for all study visits;
• Subject was in good physical health on the basis of medical history, physical examination;
• Subject and/or parents(s)/legal guardian(s) must read and signed the study-specific informed consent prior to initiation of any study procedure.

Exclusion Criteria:

• Subject ever received influenza vaccine within the previous 6 months;
• History of hypersensitivity to eggs or egg protein or similar pharmacological effects to study medication (AdimFlu-S (A/H1N1));
• Personal or family history of Guillain-Barré Syndrome;
• An acute febrile illness within the last 72 hours prior to vaccination;
• Subject with bleeding disorder or has any coagulation disorder that needs receipt of anticoagulants in the 3 weeks preceding inclusion contraindicating intramuscular injection;
• Subjects with influenza-like illness as defined by the presence of fever (temperature ≧38.5℃ ) and at least two of the following four symptoms: headache, muscle/joint aches and pains (e.g. myalgia/arthralgia), sore throat and cough;
• Female subjects who are pregnant, lactating or likely to become pregnant during the study; Women of childbearing potential disagree to use an acceptable method of contraception (e.g., hormonal contraceptives, IUD, barrier device or abstinence) throughout the study;
• Treatment with an investigational drug or device, or participation in a clinical study, within 3 months before consent;
• Immunodeficiency, immunosuppressive or household contact with immunosuppression;
• History of wheezing or bronchodilator use within 3 months prior to study vaccine;
• Receipt of live virus vaccine within 1 month prior to study vaccination or expected receipt within 2 months after first study vaccination;
• Receipt of any inactivated vaccine within 2 weeks prior to study vaccination or expected receipt vaccination within 3 weeks after the immunogenicity evaluation period;
• Receipt of any blood products, including immunoglobulin in the prior 3 months;
• Underlying condition in the investigator's opinion may be inappropriate for vaccination;
• Significant chronic illness for which inactivated influenza vaccine is recommended or commonly used.