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Sanofi H1N1 Influenza Vaccine Administered at Different Dose Levels With and Without AS03 Adjuvant in Healthy Adult and Elderly Populations

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00963157
First received: August 20, 2009
Last updated: April 11, 2013
Last verified: January 2011
  Purpose

The purpose of this study is to see how the body reacts to different strengths of the H1N1 flu shot when it is given with or without an "adjuvant." An adjuvant is a substance that may cause the body to produce more antibodies when it is given with a vaccine. This study will also compare how age affects the body's response to the H1N1 flu shot. In this study, 3 strengths of the H1N1 flu shot will be tested combined with an adjuvant. In addition, 2 strengths of the H1N1 flu shot will be tested without adjuvant. Two H1N1 flu shots of the same strength, with or without adjuvant, will be given about 3 weeks apart. Participants will include up to 800 healthy adults, approximately 500 individuals ages 18-64 and 250 individuals greater than or equal to age 65. Study procedures include: physical exam, blood samples, completing a memory aid to record vaccine side effects, medications and daily oral temperature. Participants will be involved in study related procedures for up to 13 months.


Condition Intervention Phase
Influenza
Biological: Inactivated H1N1 Vaccine
Biological: AS03
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase II Study in Healthy Adult and Elderly Populations to Assess the Safety and Immunogenicity of a Sanofi Pasteur H1N1 Influenza Vaccine Administered at Different Dose Levels Given With and Without GlaxoSmithKline AS03 Adjuvant

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 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 8 Days Following the First Dose of H1N1 Vaccine [ Time Frame: Day 0 prior to vaccination and 8 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 8 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 8 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 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.

  • 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 8 Days Following the First Dose of H1N1 Vaccine [ Time Frame: Day 0 prior to vaccination and 8 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 8 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 8 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 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.

  • Number of Participants Reporting Vaccine-associated Serious Adverse Events (SAEs) [ Time Frame: Day 0 through Day 365 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 With Hematology Laboratory Adverse Events After the First Vaccination [ Time Frame: 8-10 days after first vaccination ] [ Designated as safety issue: Yes ]
    Blood was drawn 8-10 days after vaccination to assess laboratory parameters at a central laboratory. Adverse events (AE) were any values that were Grade 1 or greater for the following parameters: prothrombin time (AE >12.6 seconds), partial thromboplastin time (>40.7 seconds), platelets (>=401,000 or <=129,000 cells/square millimeter), white blood cells (>10,800 or <3800 cells/microliter), neutrophils (>8000 or <1800 cells/microliter), and lymphocytes(>4100 or <850 cells/microliter). These parameters were not evaluated prior to enrollment as an assessment of eligibility.

  • Number of Participants With Hematology Laboratory Adverse Events After the Second Vaccination [ Time Frame: 8-10 days after second vaccination ] [ Designated as safety issue: Yes ]
    Blood was drawn 8-10 days after vaccination to assess laboratory parameters at a central laboratory. Adverse events (AE) were any values that were Grade 1 or greater for the following parameters: prothrombin time (AE >12.6 seconds), partial thromboplastin time (>40.7 seconds), platelets (>=401,000 or <=129,000 cells/square millimeter), white blood cells (>10,800 or <3800 cells/microliter), neutrophils (>8000 or <1800 cells/microliter), and lymphocytes(>4100 or <850 cells/microliter). These parameters were not evaluated prior to enrollment as an assessment of eligibility.

  • Number of Participants With Chemistry Laboratory Adverse Events After the First Vaccination [ Time Frame: 8-10 days after first vaccination ] [ Designated as safety issue: Yes ]
    Blood was drawn 8-10 days after vaccination to assess laboratory parameters at a central laboratory. Adverse events (AE) were any values that were Grade 1 or greater for the following parameters: sodium (AE >146 or <135 mEq/L), potassium (>5.3 or <3.5 mEq/L), creatinine (>1.4 mg/dL), Alanine transaminase (>52.7 U/L), Albumin (<3.2 g/dL), and total protein (<6.0 g/dL participants age 18-64 years, <5.8 g/dL participants age 65 years and older). These parameters were not evaluated prior to enrollment as an assessment of eligibility.

  • Number of Participants With Chemistry Laboratory Adverse Events After the Second Vaccination [ Time Frame: 8-10 days after second vaccination ] [ Designated as safety issue: Yes ]
    Blood was drawn 8-10 days after vaccination to assess laboratory parameters at a central laboratory. Adverse events (AE) were any values that were Grade 1 or greater for the following parameters: sodium (AE >146 or <135 mEq/L), potassium (>5.3 or <3.5 mEq/L), creatinine (>1.4 mg/dL), Alanine transaminase (>52.7 U/L), Albumin (<3.2 g/dL), and total protein (<6.0 g/dL participants age 18-64 years, <5.8 g/dL participants age 65 years and older). These parameters were not evaluated prior to enrollment as an assessment of eligibility.

  • 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, nausea, chills, arthralgia, and shivering 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, nausea, chills, arthralgia, and shivering 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 Solicited Subjective Local 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 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.

  • Number of Participants Reporting Solicited Subjective Local 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 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.

  • Number of Participants Reporting Solicited Quantitative Local 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 local reactions of redness and swelling 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 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 local reactions of redness and swelling 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 a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 8 Days Following the First Dose of H1N1 Vaccine [ Time Frame: Day 8 after the first vaccination ] [ Designated as safety issue: No ]
    Blood was collected from all participants 8 days after vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. 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 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 the first 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. 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 8 Days Following the First Dose of H1N1 Vaccine [ Time Frame: Day 8 after the first vaccination ] [ Designated as safety issue: No ]
    Blood was collected from all participants 8 days after vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. 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 the first 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. 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.


Secondary Outcome Measures:
  • 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 8 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 8 after the second vaccination ] [ Designated as safety issue: No ]
    Blood was collected from all participants 8 days after second vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. 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 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 the second vaccination ] [ Designated as safety issue: No ]
    Blood was collected from all participants 21 days after second vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. 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 18 to 64 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 180 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 180 after the second vaccination ] [ Designated as safety issue: No ]
    Blood was collected from all participants 180 days after second vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. 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 18 to 64 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 270 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 270 after the second vaccination ] [ Designated as safety issue: No ]
    Blood was collected from all participants 270 days after second vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. 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 8 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 8 after the second vaccination ] [ Designated as safety issue: No ]
    Blood was collected from all participants 8 days after second vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. 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 the second vaccination ] [ Designated as safety issue: No ]
    Blood was collected from all participants 21 days after second vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. 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 180 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 180 after the second vaccination ] [ Designated as safety issue: No ]
    Blood was collected from all participants 180 days after second vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. 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 270 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 270 after the second vaccination ] [ Designated as safety issue: No ]
    Blood was collected from all participants 270 days after second vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. 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 18 to 64 Years With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 8 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 0 prior to vaccination and 8 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 8 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 8 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.

  • 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 180 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 0 prior to vaccination and 180 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 180 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 180 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 270 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 0 prior to vaccination and 270 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 270 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 270 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 Influenza H1N1 2009 Virus 8 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 0 prior to vaccination and 8 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 8 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 8 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 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.

  • 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 180 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 0 prior to vaccination and 180 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 180 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 180 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 Influenza H1N1 2009 Virus 270 Days Following the Second Dose of H1N1 Vaccine [ Time Frame: Day 0 prior to vaccination and 270 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 270 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 270 titer was an increase by 4-fold or more.


Enrollment: 789
Study Start Date: September 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 4: 7.5 mcg H1N1 vaccine unadjuvanted
150 subjects (100 aged 18-64 and 50 aged greater than or equal to 65) to receive 7.5 mcg H1N1 vaccine unadjuvanted on Day 0 and Day 21.
Biological: Inactivated H1N1 Vaccine
Inactivated influenza H1N1 vaccine with AS03 adjuvant, delivered intramuscularly (IM) as 3.75, 7.5, or 15 micrograms per dose; and inactivated influenza H1N1 vaccine without adjuvant, delivered intramuscularly as 7.5 or 15 micrograms per dose. All doses of the vaccine with or without adjuvant will be administered as a single 0.5 mL IM injection in the deltoid muscle of the preferred arm.
Experimental: Group 5: 15 mcg H1N1 vaccine unadjuvanted
150 subjects (100 aged 18-64 and 50 aged greater than or equal to 65) to receive 15 mcg H1N1 vaccine unadjuvanted on Day 0 and Day 21.
Biological: Inactivated H1N1 Vaccine
Inactivated influenza H1N1 vaccine with AS03 adjuvant, delivered intramuscularly (IM) as 3.75, 7.5, or 15 micrograms per dose; and inactivated influenza H1N1 vaccine without adjuvant, delivered intramuscularly as 7.5 or 15 micrograms per dose. All doses of the vaccine with or without adjuvant will be administered as a single 0.5 mL IM injection in the deltoid muscle of the preferred arm.
Experimental: Group 1: 3.75 mcg H1N1 vaccine + AS03 adjuvant
150 subjects (100 aged 18-64 and 50 aged greater than or equal to 65) to receive 3.75 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.
Biological: Inactivated H1N1 Vaccine
Inactivated influenza H1N1 vaccine with AS03 adjuvant, delivered intramuscularly (IM) as 3.75, 7.5, or 15 micrograms per dose; and inactivated influenza H1N1 vaccine without adjuvant, delivered intramuscularly as 7.5 or 15 micrograms per dose. All doses of the vaccine with or without adjuvant will be administered as a single 0.5 mL IM injection in the deltoid muscle of the preferred arm.
Biological: AS03
AS03 adjuvant administered with 3.75, 7.5, or 15 mcg inactivated H1N1 vaccine.
Experimental: Group 2: 7.5 mcg H1N1 vaccine + AS03 adjuvant
150 subjects (100 aged 18-64 and 50 aged greater than or equal to 65) to receive 7.5 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.
Biological: Inactivated H1N1 Vaccine
Inactivated influenza H1N1 vaccine with AS03 adjuvant, delivered intramuscularly (IM) as 3.75, 7.5, or 15 micrograms per dose; and inactivated influenza H1N1 vaccine without adjuvant, delivered intramuscularly as 7.5 or 15 micrograms per dose. All doses of the vaccine with or without adjuvant will be administered as a single 0.5 mL IM injection in the deltoid muscle of the preferred arm.
Biological: AS03
AS03 adjuvant administered with 3.75, 7.5, or 15 mcg inactivated H1N1 vaccine.
Experimental: Group 3: 15 mcg H1N1 vaccine + AS03 adjuvant
150 subjects (100 aged 18-64 and 50 aged greater than or equal to 65) to receive 15 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.
Biological: Inactivated H1N1 Vaccine
Inactivated influenza H1N1 vaccine with AS03 adjuvant, delivered intramuscularly (IM) as 3.75, 7.5, or 15 micrograms per dose; and inactivated influenza H1N1 vaccine without adjuvant, delivered intramuscularly as 7.5 or 15 micrograms per dose. All doses of the vaccine with or without adjuvant will be administered as a single 0.5 mL IM injection in the deltoid muscle of the preferred arm.
Biological: AS03
AS03 adjuvant administered with 3.75, 7.5, or 15 mcg inactivated H1N1 vaccine.

Detailed Description:

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. This protocol will explore antibody responses following vaccination with an inactivated influenza H1N1 virus vaccine at 3 different dose levels combined with AS03 adjuvant and at 2 different dose levels administered without adjuvant. This study will assess the immune response following a single dose of vaccine with or without AS03 adjuvant, to assess whether individuals have any pre-existing 'prime' immunity, such that the initial H1N1 vaccination serves as a boost, thus conferring a more rapid time to protection with the need for fewer doses. Antibody responses will be assessed at 8 days after each dose to evaluate the development of an anamnestic response. In addition, antibody responses will be assessed 21 days after each dose. The primary objectives are: safety, to assess the safety of inactivated H1N1 vaccine when administered at the 3.75 micrograms (mcg), 7.5 mcg, or 15 mcg dose combined with AS03 adjuvant and at the 7.5 mcg or 15 mcg dose administered without adjuvant; and immunogenicity, to assess the antibody response at Day 21 following a single dose of inactivated H1N1 vaccine when administered at 3.75 mcg, 7.5 mcg, or 15 mcg dose combined with AS03 adjuvant and at the 7.5 mcg or 15 mcg dose administered without adjuvant, stratified by age of recipient. The secondary objective is immunogenicity, to assess the antibody response following 2 doses of inactivated H1N1 vaccine when administered at the 3.75 mcg, 7.5 mcg, or 15 mcg dose combined with AS03 adjuvant and at the 7.5 mcg or 15 mcg dose administered without adjuvant, stratified by age of recipient. Participants will include up to 800 healthy adults who have no history of novel influenza H1N1 2009 infection or novel influenza H1N1 2009 vaccination. This is a randomized, double-blinded, Phase II study. Subjects will be randomized into 5 groups, stratified by age (150 subjects per dose group with 100 subjects in the 18-64 years of age stratum and 50 subjects in the greater than or equal to 65 years of age stratum), to receive intramuscular inactivated influenza H1N1 vaccine at 3.75 mcg, 7.5 mcg, or 15 mcg combined with AS03 adjuvant (Groups 1, 2, and 3, respectively) or at 7.5 mcg or 15 mcg without adjuvant (Groups 4 and 5, respectively). The vaccine, with and without adjuvant, will be administered at Day 0 and Day 21. Following immunization, safety will be measured by assessment of adverse events (AEs) through 21 days following the last vaccination (Day 42 for those receiving both doses and Day 21 for those who do not receive the second dose), serious adverse events (SAEs) and new-onset chronic medical conditions through 12 months post final vaccination (Day 365 after second vaccination), and reactogenicity to vaccine for 8 days (Day 0-7) following each vaccination. Immunogenicity testing will include HAI and neutralizing antibody.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Are males or non-pregnant females age 18 and older, inclusive.
  2. Women of child-bearing potential (not surgically sterile via tubal ligation, bilateral oophorectomy or hysterectomy or who are not postmenopausal for greater than or equal to 1 year) must agree to practice adequate contraception that may include, but is not limited to, abstinence, monogamous relationship with vasectomized partner, barrier methods such as condoms, diaphragms, spermicides, intrauterine devices, and licensed hormonal methods during the study for at least 30 days following the last vaccination.
  3. Are in good health, as determined by vital signs, medical history to ensure any existing medical diagnoses or conditions are stable and not considered clinically significant, and limited physical examination. A stable chronic medical condition is defined as no change in prescription medication, dose, or frequency of medication in the last 3 months and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months. Any change that is due to change of health care provider, insurance company etc, or that is done for financial reasons, as long as in the same class of medication will not be considered a violation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome will not be considered a violation of this inclusion criterion.
  4. Have alanine aminotransferase (ALT) within normal range per local or site laboratory reference ranges.
  5. Are able to understand and comply with planned study procedures.
  6. Provide written informed consent prior to initiation of any study procedures.

Exclusion Criteria:

  1. Have a known allergy to eggs or other components of the vaccine (including squalene based adjuvants, gelatin, formaldehyde, octoxinol, thimerosal, and chicken protein).
  2. Have a positive urine or serum pregnancy test within 24 hours prior to vaccination (if female of childbearing potential), or women who are breastfeeding.
  3. Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within the preceding 36 months.
  4. Have an active neoplastic disease or a history of any hematologic malignancy.
  5. Have long term use of glucocorticoids including oral, parenteral or high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months. (Nasal and topical steroids are allowed.)
  6. Have a diagnosis of schizophrenia, bipolar disease, or other major psychiatric diagnosis.
  7. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others, within the past 10 years.
  8. Are receiving psychiatric drugs (aripiprazole, clozapine, ziprasidone, haloperidol, molindone, loxapine, thioridazine, thiothixene, pimozide, fluphenazine, risperidone, mesoridazine, quetiapine, trifluoperazine, chlorprothixene, chlorpromazine, perphenazine, trifluopromazine, olanzapine, carbamazepine, divalproex sodium, lithium carbonate or lithium citrate). Subjects who are receiving a single antidepressant drug and are stable for at least 3 months prior to enrollment, without de-compensating symptoms will be allowed to be enrolled in the study.
  9. Have a history of receiving immunoglobulin or other blood product within the 3 months prior to vaccination in this study.
  10. Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to vaccination in this study or expect to receive an experimental agent during this study (prior to the Day 386 clinic visit - 365 days after the second vaccination).
  11. Have received any live licensed vaccines within 4 weeks or inactivated licensed vaccines within 2 weeks prior to vaccination in this study or plan receipt of such vaccines within 21 days following the second vaccination. This is inclusive of seasonal influenza vaccines.
  12. Have an acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe, or would interfere with the evaluation of responses.
  13. Have a history of severe reactions following previous immunization with influenza virus vaccines.
  14. Have an acute illness, including an oral temperature greater than 100.4 degrees Fahrenheit, within 3 days prior to vaccination.
  15. Have any condition that would, in the opinion of the site investigator, place them at an unacceptable risk of injury or render them unable to meet the requirements of the protocol.
  16. Participated in a novel influenza H1N1 2009 vaccine study in the past 2 years or have a history of novel influenza H1N1 2009 infection prior to enrollment.
  17. Have known active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection or autoimmune hepatitis.
  18. Have a history of alcohol or drug abuse in the last 5 years.
  19. Plan to travel outside of North America in the time between the first vaccination and 42 days following the first vaccination.
  20. Have a history of Guillain-Barré Syndrome.
  21. Have any condition that the investigator believes may interfere with successful completion of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00963157

Locations
United States, California
Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases
Stanford, California, United States, 94305-5208
United States, Georgia
Emory Vaccine Center - The Hope Clinic
Decatur, Georgia, United States, 30030
United States, Iowa
University of Iowa - Infectious Disease Clinic
Iowa City, Iowa, United States, 52242
United States, Maryland
University of Maryland School of Medicine - Center for Vaccine Development - Baltimore
Baltimore, Maryland, United States, 21201
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Washington
Group Health Cooperative
Seattle, Washington, United States, 98101
University of Washington
Seattle, Washington, United States, 98104
Sponsors and Collaborators
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00963157     History of Changes
Other Study ID Numbers: 09-0058, N01AI80004C
Study First Received: August 20, 2009
Results First Received: November 10, 2011
Last Updated: April 11, 2013
Health Authority: United States: Institutional Review Board
United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
H1N1, influenza A viruses, vaccine, elderly

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 20, 2014