Sanofi H1N1 + TIV - Adults and Elderly

• Number of Participants Age 18 to 64 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine [ Time Frame: Day 21 after first H1N1 vaccination ] [ Designated as safety issue: No ]
  Blood was collected from all participants 21 days after vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. For Group 4, this timepoint is Study Day 42, all others it is Study Day 21. Each sample was tested at least twice according to standard operating procedures and the result of each replicate reported. A participant is counted if the geometric mean of the replicate values was 1:40 or greater.
  
  
• Number of Participants Age 65 Years and Older With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine [ Time Frame: Day 21 after first H1N1 vaccination ] [ Designated as safety issue: No ]
  Blood was collected from all participants 21 days after vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. For Group 4, this timepoint is Study Day 42, all others it is Study Day 21. Each sample was tested at least twice according to standard operating procedures and the result of each replicate reported. A participant is counted if the geometric mean of the replicate values was 1:40 or greater.
  
  
• Number of Participants Reporting Vaccine-associated Serious Adverse Events (SAEs) [ Time Frame: Day 0 through Day 180 after the last vaccination ] [ Designated as safety issue: Yes ]
  Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required in-patient hospitalization or prolongation thereof; resulted in a congenital anomaly/birth defect; may have jeopardized the participant or required intervention to prevent one of these outcomes; or was described as Guillain-Barré Syndrome. Association to vaccination was determined by a study clinician licensed to make medical diagnoses.
  
  
• Number of Participants Age 18 to 64 Years With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine [ Time Frame: Day 0 prior to vaccination and 21 days after the first H1N1 vaccination ] [ Designated as safety issue: No ]
  Blood was collected from participants for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. A participant met the threshold of a 4-fold rise in titer if the Day 0 titer was less than 1:10 (the assay's lowest level of detection) and the Day 21 post first H1N1 vaccination titer was 1:40 or greater, or the Day 0 titer was greater than or equal to 1:10 and the Day 21 titer was an increase by 4-fold or more. Day 21 post first H1N1 vaccination is Study Day 42 for Group 4, and is Study Day 21 for all other groups.
  
  
• Number of Participants Age 65 Years and Older With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine [ Time Frame: Day 0 prior to vaccination and 21 days after the first H1N1 vaccination ] [ Designated as safety issue: No ]
  Blood was collected from participants for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. A participant met the threshold of a 4-fold rise in titer if the Day 0 titer was less than 1:10 (the assay's lowest level of detection) and the Day 21 post first H1N1 vaccination titer was 1:40 or greater, or the Day 0 titer was greater than or equal to 1:10 and the Day 21 titer was an increase by 4-fold or more. Day 21 post first H1N1 vaccination is Study Day 42 for Group 4, and is Study Day 21 for all other groups.
  
  
• Number of Participants Reporting Solicited Subjective Systemic Reactions After the First Vaccination [ Time Frame: Within 8 days (Day 0-7) post first vaccination ] [ Designated as safety issue: Yes ]
  Participants maintained a memory aid to record daily the occurrence of systemic symptoms of feverishness, malaise, myalgia, headache, and nausea for 8 days (Day 0-7) after vaccination based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.
  
  
• Number of Participants Reporting Solicited Subjective Systemic Reactions After the Second Vaccination [ Time Frame: Within 8 days (Day 0-7) post second vaccination ] [ Designated as safety issue: Yes ]
  Participants maintained a memory aid to record daily the occurrence of systemic symptoms of feverishness, malaise, myalgia, headache, and nausea for 8 days (Day 0-7) after vaccination based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.
  
  
• Number of Participants Reporting Solicited Subjective Systemic Reactions After the Third Vaccination [ Time Frame: Within 8 days (Day 0-7) post third vaccination ] [ Designated as safety issue: Yes ]
  Participants maintained a memory aid to record daily the occurrence of systemic symptoms of feverishness, malaise, myalgia, headache, and nausea for 8 days (Day 0-7) after vaccination based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.
  
  
• Number of Participants Reporting Fever After the First Vaccination [ Time Frame: Within 8 days (Day 0-7) post first vaccination ] [ Designated as safety issue: Yes ]
  Participants were provided a thermometer and a memory aid to record daily oral temperatures for 8 days (Day 0-7) after vaccination. Participants are counted as experiencing fever if they reported oral temperatures of 38 degrees Celsius or higher on any of the 8 days.
  
  
• Number of Participants Reporting Fever After the Second Vaccination [ Time Frame: Within 8 days (Day 0-7) post second vaccination ] [ Designated as safety issue: Yes ]
  Participants were provided a thermometer and a memory aid to record daily oral temperatures for 8 days (Day 0-7) after vaccination. Participants are counted as experiencing fever if they reported oral temperatures of 38 degrees Celsius or higher on any of the 8 days.
  
  
• Number of Participants Reporting Fever After the Third Vaccination [ Time Frame: Within 8 days (Day 0-7) post third vaccination ] [ Designated as safety issue: Yes ]
  Participants were provided a thermometer and a memory aid to record daily oral temperatures for 8 days (Day 0-7) after vaccination. Participants are counted as experiencing fever if they reported oral temperatures of 38 degrees Celsius or higher on any of the 8 days.
  
  
• Number of Participants Reporting Solicited Subjective Local Reactions After the First H1N1 Vaccination [ Time Frame: Within 8 days (Day 0-7) post first H1N1 vaccination ] [ Designated as safety issue: Yes ]
  Participants maintained a memory aid to record daily the occurrence of local symptoms of pain, tenderness and swelling for 8 days (Day 0-7) after vaccination based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days. First H1N1 vaccination was given on Study Day 0 for Groups 1, 2 and 3, and on Study Day 21 for Group 4.
  
  
• Number of Participants Reporting Solicited Subjective Local Reactions After the Second H1N1 Vaccination [ Time Frame: Within 8 days (Day 0-7) post second H1N1 vaccination ] [ Designated as safety issue: Yes ]
  Participants maintained a memory aid to record daily the occurrence of local symptoms of pain, tenderness and swelling for 8 days (Day 0-7) after vaccination based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days. Second H1N1 vaccination was given on Study Day 21 for Groups 1, 2 and 3, and on Study Day 42 for Group 4.
  
  
• Number of Participants Reporting Solicited Subjective Local Reactions After the TIV Vaccination [ Time Frame: Within 8 days (Day 0-7) post TIV vaccination ] [ Designated as safety issue: Yes ]
  Participants maintained a memory aid to record daily the occurrence of local symptoms of pain, tenderness and swelling for 8 days (Day 0-7) after vaccination based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days. The TIV vaccination was given on Study Day 42 for Group 1, Study Day 0 for Groups 2 and 4, and on Study Day 21 for Group 3.
  
  
• Number of Participants Reporting Solicited Subjective Local Reactions After the First Placebo Vaccination [ Time Frame: Within 8 days (Day 0-7) post first placebo vaccination ] [ Designated as safety issue: Yes ]
  Participants maintained a memory aid to record daily the occurrence of local symptoms of pain, tenderness and swelling for 8 days (Day 0-7) after vaccination based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days. The first placebo vaccination was given on Study Day 0 for Groups 1, 3 and 4, and on Study Day 21 for Group 2.
  
  
• Number of Participants Reporting Solicited Subjective Local Reactions After the Second Placebo Vaccination [ Time Frame: Within 8 days (Day 0-7) post second placebo vaccination ] [ Designated as safety issue: Yes ]
  Participants maintained a memory aid to record daily the occurrence of local symptoms of pain, tenderness and swelling for 8 days (Day 0-7) after vaccination based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days. The second placebo vaccination was given on Study Day 21 for Groups 1 and 4, on Study Day 42 for Groups 2 and 3.
  
  
• Number of Participants Reporting Solicited Quantitative Local Reactions After the First H1N1 Vaccination [ Time Frame: Within 8 days (Day 0-7) post first H1N1 vaccination ] [ Designated as safety issue: Yes ]
  Participants maintained a memory aid to record daily the occurrence of local reactions of swelling and redness for 8 days (Day 0-7) after vaccination. If the reaction was present, the maximum diameter was measured in millimeters (mm). Participants are counted if they were reported as experiencing the reaction with any measurement greater than 0 mm on any of the 8 days.
  
  
• Number of Participants Reporting Solicited Quantitative Local Reactions After the Second H1N1 Vaccination [ Time Frame: Within 8 days (Day 0-7) post second H1N1 vaccination ] [ Designated as safety issue: Yes ]
  Participants maintained a memory aid to record daily the occurrence of local reactions of swelling and redness for 8 days (Day 0-7) after vaccination. If the reaction was present, the maximum diameter was measured in millimeters (mm). Participants are counted if they were reported as experiencing the reaction with any measurement greater than 0 mm on any of the 8 days.
  
  
• Number of Participants Reporting Solicited Quantitative Local Reactions After the TIV Vaccination [ Time Frame: Within 8 days (Day 0-7) post TIV vaccination ] [ Designated as safety issue: Yes ]
  Participants maintained a memory aid to record daily the occurrence of local reactions of swelling and redness for 8 days (Day 0-7) after vaccination. If the reaction was present, the maximum diameter was measured in millimeters (mm). Participants are counted if they were reported as experiencing the reaction with any measurement greater than 0 mm on any of the 8 days.
  
  
• Number of Participants Reporting Solicited Quantitative Local Reactions After the First Placebo Vaccination [ Time Frame: Within 8 days (Day 0-7) post first placebo vaccination ] [ Designated as safety issue: Yes ]
  Participants maintained a memory aid to record daily the occurrence of local reactions of swelling and redness for 8 days (Day 0-7) after vaccination. If the reaction was present, the maximum diameter was measured in millimeters (mm). Participants are counted if they were reported as experiencing the reaction with any measurement greater than 0 mm on any of the 8 days.
  
  
• Number of Participants Reporting Solicited Quantitative Local Reactions After the Second Placebo Vaccination [ Time Frame: Within 8 days (Day 0-7) post second placebo vaccination ] [ Designated as safety issue: Yes ]
  Participants maintained a memory aid to record daily the occurrence of local reactions of swelling and redness for 8 days (Day 0-7) after vaccination. If the reaction was present, the maximum diameter was measured in millimeters (mm). Participants are counted if they were reported as experiencing the reaction with any measurement greater than 0 mm on any of the 8 days.
  
  

• Number of Participants Age 18 to 64 Years With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Virus Strains in the 2009-2010 Trivalent Influenza Vaccine (TIV) 21 Days Following the Last Vaccination [ Time Frame: Day 63 ] [ Designated as safety issue: No ]
  Blood was collected from participants for testing in the HAI assay against each strain in the 2009-2010 trivalent influenza vaccine. A participant met the threshold of a 4-fold rise in titer if the Day 0 titer was less than 1:10 (the assay's lowest level of detection) and the Day 63 titer was 1:40 or greater, or the Day 0 titer was greater than or equal to 1:10 and the Day 63 titer was an increase by 4-fold or more.
  
  
• Number of Participants Age 65 Years and Older With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Virus Strains in the 2009-2010 Trivalent Influenza Vaccine (TIV) 21 Days Following the Last Vaccination [ Time Frame: Day 63 ] [ Designated as safety issue: No ]
  Blood was collected from participants for testing in the HAI assay against each strain in the 2009-2010 trivalent influenza vaccine. A participant met the threshold of a 4-fold rise in titer if the Day 0 titer was less than 1:10 (the assay's lowest level of detection) and the Day 63 titer was 1:40 or greater, or the Day 0 titer was greater than or equal to 1:10 and the Day 63 titer was an increase by 4-fold or more.
  
  
• Number of Participants Age 18 to 64 Years With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 0 prior to vaccination and 21 days after the second H1N1 vaccination ] [ Designated as safety issue: No ]
  Blood was collected from participants for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. A participant met the threshold of a 4-fold rise in titer if the Day 0 titer was less than 1:10 (the assay's lowest level of detection) and the Day 21 post second H1N1 vaccination titer was 1:40 or greater, or the Day 0 titer was greater than or equal to 1:10 and the Day 21 titer was an increase by 4-fold or more. Day 21 post second H1N1 vaccination is Study Day 63 for Group 4, and is Study Day 42 for all other groups.
  
  
• Number of Participants Age 65 Years and Older With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 0 prior to vaccination and 21 days after the second H1N1 vaccination ] [ Designated as safety issue: No ]
  Blood was collected from participants for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. A participant met the threshold of a 4-fold rise in titer if the Day 0 titer was less than 1:10 (the assay's lowest level of detection) and the Day 21 post second H1N1 vaccination titer was 1:40 or greater, or the Day 0 titer was greater than or equal to 1:10 and the Day 21 titer was an increase by 4-fold or more. Day 21 post second H1N1 vaccination is Study Day 63 for Group 4, and is Study Day 42 for all other groups.
  
  
• Number of Participants Age 18 to 64 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Virus Strains in the 2009-2010 Trivalent Influenza Vaccine (TIV) 21 Days Following the Last Vaccination [ Time Frame: Day 63 ] [ Designated as safety issue: No ]
  Blood was collected from participants 21 days after the last vaccination for testing in the HAI assay against each strain in the 2009-2010 trivalent influenza vaccine. Each sample was tested according to standard operating procedures. A participant is counted if the value at the Day 63 timepoint was 1:40 or greater.
  
  
• Number of Participants Age 65 Years and Older With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Virus Strains in the 2009-2010 Trivalent Influenza Vaccine (TIV) 21 Days Following the Last Vaccination [ Time Frame: Day 63 ] [ Designated as safety issue: No ]
  Blood was collected from participants 21 days after the last vaccination for testing in the HAI assay against each strain in the 2009-2010 trivalent influenza vaccine. Each sample was tested according to standard operating procedures. A participant is counted if the value at the Day 63 timepoint was 1:40 or greater.
  
  
• Number of Participants Age 18 to 64 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 21 after second H1N1 vaccination ] [ Designated as safety issue: No ]
  Blood was collected from all participants 21 days after vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. For Group 4, this timepoint is Study Day 63, all others it is Study Day 42. Each sample was tested at least twice according to standard operating procedures and the result of each replicate reported. A participant is counted if the geometric mean of the replicate values was 1:40 or greater.
  
  
• Number of Participants Age 65 Years and Older With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 21 after second H1N1 vaccination ] [ Designated as safety issue: No ]
  Blood was collected from all participants 21 days after vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. For Group 4, this timepoint is Study Day 63, all others it is Study Day 42. Each sample was tested at least twice according to standard operating procedures and the result of each replicate reported. A participant is counted if the geometric mean of the replicate values was 1:40 or greater.
  
  

Recently, a novel swine-origin influenza A/H1N1 virus was identified as a significant cause of febrile respiratory illnesses in Mexico and the United States. It rapidly spread to many countries around the world, prompting the World Health Organization to declare a pandemic on June 11, 2009. Data from several cohorts in different age groups that received licensed trivalent seasonal influenza vaccines suggest that these vaccines are unlikely to provide protection against the new virus. Adults are more likely to have measurable levels of serum hemagglutination inhibition assay (HAI) or neutralizing antibody than are children. These data indicate the need to develop vaccines against the new H1N1 strain and suggest that different vaccine strategies (e.g., number of doses, need for adjuvant) may be appropriate for persons in different age groups. If the novel influenza H1N1 2009 virus continues to circulate, it is possible that it will co-circulate with the non-pandemic seasonal influenza strains. In this situation, it might be beneficial to co-administer an H1N1 vaccine concurrent with the seasonal inactivated influenza vaccine. This protocol explores if vaccination with the 2009-2010 licensed seasonal trivalent influenza vaccine (TIV) has an effect on antibody response to the novel influenza H1N1 2009 virus and examines if receiving the H1N1 vaccine either concurrent with, prior to, or following the seasonal influenza vaccine affects the antibody response to the seasonal influenza vaccine. This is a randomized, double-blinded, Phase II study in up to 850 healthy males and non-pregnant females, aged 18 and older. The study investigates the safety, reactogenicity, and immunogenicity of an inactivated influenza H1N1 virus vaccine when given concurrent with or sequentially with (before or after) TIV. The primary safety objective is to assess the safety of the unadjuvanted, inactivated H1N1 influenza vaccine when administered either concurrent with, prior to, or following licensed seasonal influenza vaccination. The primary immunogenicity objective is to assess the effect of TIV on antibody response to unadjuvanted, inactivated influenza H1N1 vaccine as assessed by hemagglutination inhibition assay (HAI), stratified by age of recipient. The secondary objective is immunogenicity, to assess the effect of H1N1 vaccine administration on antibody response to TIV as assessed by HAI, stratified by age of recipient. Subjects will be randomized into 4 groups, stratified by age (200 subjects per group with 100 subjects per age stratum, 18-64 or greater than or equal to 65 years of age). Group 1 will receive two 15 microgram (mcg) doses of H1N1 vaccine at Days 0 and 21 followed by TIV on Day 42. Group 2 will receive two 15 mcg doses of H1N1 vaccine of which the first dose is administered concurrently with TIV. Group 3 will receive two 15 mcg doses of H1N1 vaccine of which the second dose is administered concurrently with TIV. Group 4 will receive TIV administered on Day 0 followed by two 15 mcg doses of H1N1 vaccine on Days 21 and 42. In order to maintain the blind, subjects will also receive a placebo (normal saline) so that two products will be administered at both Days 0 and 21, and one product will be administered at Day 42 for all groups. Following immunization, safety will be measured by assessment of adverse events for 21 days following the last vaccination (Day 42 for those who do not receive the second dose), serious adverse events and new-onset chronic medical conditions for 8 months post the first vaccination (Day 222), and reactogenicity to the vaccines for 8 days following each vaccination (Day 0-7). Immunogenicity testing will include HAI