Influenza
Conditions
Keywords
vaccines, immunogenicity, human, safety, influenza
Brief summary
The purpose of this Phase 3, observer-blind, placebo-controlled, multi-center study is to characterize the immunogenicity & safety of the investigation vaccination regimen of GSK 1557484A vaccine given to adults aged ≥18 years.
Interventions
Two intramuscular injections at Days 0 and 21.
BIOLOGICALPlacebo
Two intramuscular injections at Days 0 and 21.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* A male or female 18 years of age or greater at the time of the first vaccination. * Written informed consent obtained from the subject. * Among 18 to 49 year old subjects, good general health as established by medical history and clinical examination before entering into the study. * Among subjects \> 49 years of age, stable health status within 1 month prior to enrollment. * Access to a consistent means of telephone contact. * Comprehension of the study requirements, ability to comprehend and comply with procedures for collection of short- and long-term safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits.
Exclusion criteria
* Evidence of substance abuse or of neurological or psychiatric diagnoses which, even if clinically stable, are deemed by the investigator to render the potential subjectunable/unlikely to provide accurate safety reports. * Diagnosed with cancer, or treatment for cancer, within 3 years. * An oral temperature ≥37.8º C, or acute symptoms greater than mild severity on the scheduled date of first vaccination. * Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus infection. * Receipt of systemic glucocorticoids within 1 month of study enrollment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrollment. * Any significant disorder of coagulation or treatment with Coumadin derivatives or heparin. * Administration of any vaccines within 30 days before study enrollment. * Previous administration of any H5N1 vaccine. * Use of any investigational or non-registered product or planned participation in another investigational study within 30 days prior to study enrollment, or during the 364 days following the first test article dose. Use of any investigational or non-registered product with immunosuppressive properties is exclusionary at any time during the trial. * Receipt of any immunoglobulins and/or any blood products within 3 months of study enrollment or planned administration of any of these products during the study period. * Any known or suspected allergy to any constituent of influenza vaccines; a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine. * Known pregnancy or a positive urine beta-human chorionic gonadotropin test result prior to either vaccination. * Lactating or nursing. * Women of child bearing potential who lack a history of reliable contraceptive practices. The provision of this history does NOT replace the requirement to perform, and obtain negative results in pregnancy urine tests prior to treatments. * Known use of an analgesic or antipyretic medication within 12 hours prior to first treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Any Unsolicited Adverse Events (AEs). | During a 21-day follow-up period for each vaccine administration, as well as overall (Day 0 through Day 84) | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. |
| Number of Seroconverted Subjects Against A/Indonesia/5/2005 (H5N1) | At Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2) | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination (Day 0) reciprocal HI titer \< 1:10 and a post-vaccination (Day 42) reciprocal titer ≥ 1:40, or a pre-vaccination reciprocal HI titer ≥ 1:10 and at least a 4-fold increase in post-vaccination reciprocal titer against A/Indonesia/5/05 virus 21 days after the second dose of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted. |
| Number of Subjects With Serious Adverse Events (SAEs) | From Day 0 through Day 182 and through Day 379. | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. |
| Number of Subjects With Medically Attended Events (MAEs) | From Day 0 through Day 182 and through Day 364. | — |
| Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) | At Day 0 and Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2) | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. |
| Number of Subjects With Any Solicited Local Symptoms. | During a 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after each vaccine administration | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. |
| Number of Subjects With Any Solicited General Symptoms. | During a 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after each vaccine administration | Assessed solicited general symptoms were fatigue, headache, joint pain at other locations, muscle aches, shivering, sweating and temperature\[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Serum Reciprocal HI Antibodies Against A/Indonesia/5/2005 Equal to or Above (≥) 1:10 | At Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2) | — |
| Number of Subjects With A/Indonesia/5/05 Antibody Titers ≥ 1:10 | At Month 6 (Day 182) post Dose 1 | — |
| Number of Seroconverted Subjects Against A/Indonesia/5/2005 (H5N1) | At Month 6 (Day 182) after Dose 1 | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination (Day 0) reciprocal HI titer \< 1:10 and a post-vaccination (Day 42) reciprocal titer ≥ 1:40, or a pre-vaccination reciprocal HI titer ≥ 1:10 and at least a 4-fold increase in post-vaccination reciprocal titer against A/Indonesia/5/05 virus 21 days after the second dose of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted. |
| Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) | At Month 6 (Day 182) after Dose 1 | — |
| Titers for Serum HI Antibodies Against A/Indonesia/5/05 (H5N1) | At Month 6 (Day 182) after Dose 1 | Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was ≥ 1:10. |
| Number of Subjects With a Vaccine Response to the Vaccine-homologous Virus and Drift Variant H5N1 Virus, as Assessed by Microneutralization Assays. | At Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2) | Virus antibody response rates were defined as the number of subjects with antibody titers at Day 42 ≥ 4-fold the pre-vaccination antibody titers. The 2 strains assessed were Flu A/Indonesia/5/05 and Flu A/Vietnam/1194/04. |
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1) as Assessed by Microneutralization Assays | At Day 0 and Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2) | Titers were expressed as Geometric Mean Titers (GMTs). |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Influenza A (H5N1) 18-64Y Group Subjects aged 18-64 years, who received 2 doses of the Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted, formulations A, B, or C in approximately equal proportions, at Days 0 and 21. The first dose was administered in the deltoid region of the non-dominant arm. The second dose was administered in the deltoid region of the dominant arm. | 2,304 |
| Placebo 18-64Y Group Subjects aged 18-64 years, who received 2 doses of placebo at Days 0 and 21. The first dose was administered in the deltoid region of the non-dominant arm. The second dose was administered in the deltoid region of the dominant arm. | 768 |
| Influenza A (H5N1) >64Y Group Influenza A (H5N1) \>64Y Group Subjects aged \> 64 years, who received 2 doses of the Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted, formulations A, B, or C in approximately equal proportions, at Days 0 and 21. The first dose was administered in the deltoid region of the non-dominant arm. The second dose was administered in the deltoid region of the dominant arm. | 1,118 |
| Placebo >64Y Group Subjects aged \> 64 years, who received 2 doses of placebo at Days 0 and 21. The first dose was administered in the deltoid region of the non-dominant arm. The second dose was administered in the deltoid region of the dominant arm. | 371 |
| Total | 4,561 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 3 | 2 | 2 |
| Overall Study | Lost to Follow-up | 5 | 7 | 0 | 0 |
| Overall Study | Other | 51 | 8 | 15 | 5 |
Baseline characteristics
| Characteristic | Influenza A (H5N1) 18-64Y Group | Placebo 18-64Y Group | Influenza A (H5N1) >64Y Group | Placebo >64Y Group | Total |
|---|---|---|---|---|---|
| Age, Continuous | 38.5 Years STANDARD_DEVIATION 13.64 | 38.7 Years STANDARD_DEVIATION 13.58 | 71.9 Years STANDARD_DEVIATION 5.49 | 72.1 Years STANDARD_DEVIATION 5.41 | 49.5 Years STANDARD_DEVIATION 19.5 |
| Sex: Female, Male Female | 1328 Participants | 424 Participants | 621 Participants | 196 Participants | 2569 Participants |
| Sex: Female, Male Male | 976 Participants | 344 Participants | 497 Participants | 175 Participants | 1992 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2,087 / 2,304 | 405 / 768 | 866 / 1,118 | 141 / 371 |
| serious Total, serious adverse events | 24 / 2,304 | 7 / 768 | 43 / 1,118 | 14 / 371 |
Outcome results
Primary
Number of Seroconverted Subjects Against A/Indonesia/5/2005 (H5N1)
A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination (Day 0) reciprocal HI titer \< 1:10 and a post-vaccination (Day 42) reciprocal titer ≥ 1:40, or a pre-vaccination reciprocal HI titer ≥ 1:10 and at least a 4-fold increase in post-vaccination reciprocal titer against A/Indonesia/5/05 virus 21 days after the second dose of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted.
Time frame: At Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2)
Population: The analysis was based on the ATP cohort for analysis of immunogenicity, which included all evaluable subjects (meeting all eligibility criteria, complying with the procedures in the protocol, with no elimination criteria during the study) with a complete set of data concerning immunogenicity primary outcome variables available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Influenza A (H5N1) 18-64Y Group | Number of Seroconverted Subjects Against A/Indonesia/5/2005 (H5N1) | 1427 Subjects |
| Placebo 18-64Y Group | Number of Seroconverted Subjects Against A/Indonesia/5/2005 (H5N1) | 1 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Seroconverted Subjects Against A/Indonesia/5/2005 (H5N1) | 293 Subjects |
| Placebo >64Y Group | Number of Seroconverted Subjects Against A/Indonesia/5/2005 (H5N1) | 1 Subjects |
Primary
Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1)
A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40.
Time frame: At Day 0 and Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2)
Population: The analysis was based on the ATP cohort for analysis of immunogenicity, which included all evaluable subjects (meeting all eligibility criteria, complying with the procedures in the protocol, with no elimination criteria during the study) with a complete set of data concerning immunogenicity primary outcome variables available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Influenza A (H5N1) 18-64Y Group | Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) | Day 0 | 5 Subjects |
| Influenza A (H5N1) 18-64Y Group | Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) | Day 42 | 1467 Subjects |
| Placebo 18-64Y Group | Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) | Day 42 | 1 Subjects |
| Placebo 18-64Y Group | Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) | Day 0 | 0 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) | Day 0 | 9 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) | Day 42 | 334 Subjects |
| Placebo >64Y Group | Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) | Day 0 | 0 Subjects |
| Placebo >64Y Group | Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) | Day 42 | 1 Subjects |
Primary
Number of Subjects With Any Solicited General Symptoms.
Assessed solicited general symptoms were fatigue, headache, joint pain at other locations, muscle aches, shivering, sweating and temperature\[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade.
Time frame: During a 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after each vaccine administration
Population: The analysis was based on the Total Vaccinated cohort, on subjects with symptom sheets completed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Any Solicited General Symptoms. | Muscle aches | 1188 Subjects |
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Any Solicited General Symptoms. | Joint pain at other location | 645 Subjects |
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Any Solicited General Symptoms. | Temperature | 121 Subjects |
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Any Solicited General Symptoms. | Headache | 932 Subjects |
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Any Solicited General Symptoms. | Fatigue | 890 Subjects |
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Any Solicited General Symptoms. | Shivering | 456 Subjects |
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Any Solicited General Symptoms. | Sweating | 314 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Any Solicited General Symptoms. | Muscle aches | 175 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Any Solicited General Symptoms. | Sweating | 67 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Any Solicited General Symptoms. | Shivering | 87 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Any Solicited General Symptoms. | Headache | 249 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Any Solicited General Symptoms. | Fatigue | 189 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Any Solicited General Symptoms. | Temperature | 32 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Any Solicited General Symptoms. | Joint pain at other location | 97 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Any Solicited General Symptoms. | Shivering | 107 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Any Solicited General Symptoms. | Muscle aches | 338 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Any Solicited General Symptoms. | Headache | 247 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Any Solicited General Symptoms. | Sweating | 48 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Any Solicited General Symptoms. | Joint pain at other location | 208 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Any Solicited General Symptoms. | Fatigue | 258 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Any Solicited General Symptoms. | Temperature | 35 Subjects |
| Placebo >64Y Group | Number of Subjects With Any Solicited General Symptoms. | Temperature | 6 Subjects |
| Placebo >64Y Group | Number of Subjects With Any Solicited General Symptoms. | Headache | 63 Subjects |
| Placebo >64Y Group | Number of Subjects With Any Solicited General Symptoms. | Joint pain at other location | 39 Subjects |
| Placebo >64Y Group | Number of Subjects With Any Solicited General Symptoms. | Muscle aches | 56 Subjects |
| Placebo >64Y Group | Number of Subjects With Any Solicited General Symptoms. | Shivering | 22 Subjects |
| Placebo >64Y Group | Number of Subjects With Any Solicited General Symptoms. | Sweating | 15 Subjects |
| Placebo >64Y Group | Number of Subjects With Any Solicited General Symptoms. | Fatigue | 64 Subjects |
| Influenza A (H5N1) Group | Number of Subjects With Any Solicited General Symptoms. | Fatigue | 1148 Subjects |
| Influenza A (H5N1) Group | Number of Subjects With Any Solicited General Symptoms. | Muscle aches | 1526 Subjects |
| Influenza A (H5N1) Group | Number of Subjects With Any Solicited General Symptoms. | Shivering | 563 Subjects |
| Influenza A (H5N1) Group | Number of Subjects With Any Solicited General Symptoms. | Sweating | 362 Subjects |
| Influenza A (H5N1) Group | Number of Subjects With Any Solicited General Symptoms. | Temperature | 156 Subjects |
| Influenza A (H5N1) Group | Number of Subjects With Any Solicited General Symptoms. | Headache | 1179 Subjects |
| Influenza A (H5N1) Group | Number of Subjects With Any Solicited General Symptoms. | Joint pain at other location | 853 Subjects |
| Placebo Group | Number of Subjects With Any Solicited General Symptoms. | Fatigue | 253 Subjects |
| Placebo Group | Number of Subjects With Any Solicited General Symptoms. | Headache | 312 Subjects |
| Placebo Group | Number of Subjects With Any Solicited General Symptoms. | Sweating | 109 Subjects |
| Placebo Group | Number of Subjects With Any Solicited General Symptoms. | Shivering | 109 Subjects |
| Placebo Group | Number of Subjects With Any Solicited General Symptoms. | Muscle aches | 231 Subjects |
| Placebo Group | Number of Subjects With Any Solicited General Symptoms. | Temperature | 109 Subjects |
| Placebo Group | Number of Subjects With Any Solicited General Symptoms. | Joint pain at other location | 136 Subjects |
Primary
Number of Subjects With Any Solicited Local Symptoms.
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.
Time frame: During a 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after each vaccine administration
Population: The analysis was based on the Total Vaccinated cohort, on subjects with symptom sheets completed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Any Solicited Local Symptoms. | Redness | 181 Subjects |
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Any Solicited Local Symptoms. | Pain | 2024 Subjects |
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Any Solicited Local Symptoms. | Swelling | 241 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Any Solicited Local Symptoms. | Redness | 7 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Any Solicited Local Symptoms. | Pain | 171 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Any Solicited Local Symptoms. | Swelling | 7 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Any Solicited Local Symptoms. | Redness | 106 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Any Solicited Local Symptoms. | Pain | 784 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Any Solicited Local Symptoms. | Swelling | 110 Subjects |
| Placebo >64Y Group | Number of Subjects With Any Solicited Local Symptoms. | Redness | 1 Subjects |
| Placebo >64Y Group | Number of Subjects With Any Solicited Local Symptoms. | Pain | 53 Subjects |
| Placebo >64Y Group | Number of Subjects With Any Solicited Local Symptoms. | Swelling | 1 Subjects |
| Influenza A (H5N1) Group | Number of Subjects With Any Solicited Local Symptoms. | Redness | 287 Subjects |
| Influenza A (H5N1) Group | Number of Subjects With Any Solicited Local Symptoms. | Pain | 2808 Subjects |
| Influenza A (H5N1) Group | Number of Subjects With Any Solicited Local Symptoms. | Swelling | 351 Subjects |
| Placebo Group | Number of Subjects With Any Solicited Local Symptoms. | Pain | 224 Subjects |
| Placebo Group | Number of Subjects With Any Solicited Local Symptoms. | Swelling | 8 Subjects |
| Placebo Group | Number of Subjects With Any Solicited Local Symptoms. | Redness | 8 Subjects |
Primary
Number of Subjects With Any Unsolicited Adverse Events (AEs).
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Time frame: During a 21-day follow-up period for each vaccine administration, as well as overall (Day 0 through Day 84)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Any Unsolicited Adverse Events (AEs). | Unsolicited AEs Days 0-21 | 914 Subjects |
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Any Unsolicited Adverse Events (AEs). | Unsolicited AEs Days 0-84 | 1017 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Any Unsolicited Adverse Events (AEs). | Unsolicited AEs Days 0-84 | 321 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Any Unsolicited Adverse Events (AEs). | Unsolicited AEs Days 0-21 | 289 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Any Unsolicited Adverse Events (AEs). | Unsolicited AEs Days 0-21 | 399 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Any Unsolicited Adverse Events (AEs). | Unsolicited AEs Days 0-84 | 467 Subjects |
| Placebo >64Y Group | Number of Subjects With Any Unsolicited Adverse Events (AEs). | Unsolicited AEs Days 0-21 | 113 Subjects |
| Placebo >64Y Group | Number of Subjects With Any Unsolicited Adverse Events (AEs). | Unsolicited AEs Days 0-84 | 130 Subjects |
Primary
Number of Subjects With Medically Attended Events (MAEs)
Time frame: From Day 0 through Day 182 and through Day 364.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Medically Attended Events (MAEs) | Subjects with MAEs Days 0-182 | 480 Subjects |
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Medically Attended Events (MAEs) | Subjects with MAEs Days 0-379 | 627 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Medically Attended Events (MAEs) | Subjects with MAEs Days 0-379 | 212 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Medically Attended Events (MAEs) | Subjects with MAEs Days 0-182 | 154 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Medically Attended Events (MAEs) | Subjects with MAEs Days 0-182 | 298 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Medically Attended Events (MAEs) | Subjects with MAEs Days 0-379 | 400 Subjects |
| Placebo >64Y Group | Number of Subjects With Medically Attended Events (MAEs) | Subjects with MAEs Days 0-182 | 92 Subjects |
| Placebo >64Y Group | Number of Subjects With Medically Attended Events (MAEs) | Subjects with MAEs Days 0-379 | 134 Subjects |
Primary
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time frame: From Day 0 through Day 182 and through Day 379.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Serious Adverse Events (SAEs) | Subjects with SAEs Days 0-182 | 24 Subjects |
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Serious Adverse Events (SAEs) | Subjects with SAEs Days 0-379 | 46 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Serious Adverse Events (SAEs) | Subjects with SAEs Days 0-379 | 15 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Serious Adverse Events (SAEs) | Subjects with SAEs Days 0-182 | 7 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Serious Adverse Events (SAEs) | Subjects with SAEs Days 0-182 | 43 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Serious Adverse Events (SAEs) | Subjects with SAEs Days 0-379 | 65 Subjects |
| Placebo >64Y Group | Number of Subjects With Serious Adverse Events (SAEs) | Subjects with SAEs Days 0-182 | 14 Subjects |
| Placebo >64Y Group | Number of Subjects With Serious Adverse Events (SAEs) | Subjects with SAEs Days 0-379 | 30 Subjects |
Secondary
Number of Seroconverted Subjects Against A/Indonesia/5/2005 (H5N1)
A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination (Day 0) reciprocal HI titer \< 1:10 and a post-vaccination (Day 42) reciprocal titer ≥ 1:40, or a pre-vaccination reciprocal HI titer ≥ 1:10 and at least a 4-fold increase in post-vaccination reciprocal titer against A/Indonesia/5/05 virus 21 days after the second dose of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted.
Time frame: At Month 6 (Day 182) after Dose 1
Population: The analysis was based on the ATP cohort for analysis of immunogenicity - Month 6, which included all evaluable subjects (meeting all eligibility criteria, complying with the procedures in the protocol, with no elimination criteria during the study) with a complete set of data concerning immunogenicity primary outcome variables available at Month 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Influenza A (H5N1) 18-64Y Group | Number of Seroconverted Subjects Against A/Indonesia/5/2005 (H5N1) | 225 Subjects |
| Placebo 18-64Y Group | Number of Seroconverted Subjects Against A/Indonesia/5/2005 (H5N1) | 1 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Seroconverted Subjects Against A/Indonesia/5/2005 (H5N1) | 59 Subjects |
| Placebo >64Y Group | Number of Seroconverted Subjects Against A/Indonesia/5/2005 (H5N1) | 0 Subjects |
Secondary
Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1)
Time frame: At Month 6 (Day 182) after Dose 1
Population: The analysis was based on the ATP cohort for analysis of immunogenicity - Month 6, which included all evaluable subjects (meeting all eligibility criteria, complying with the procedures in the protocol, with no elimination criteria during the study) with a complete set of data concerning immunogenicity primary outcome variables available at Month 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Influenza A (H5N1) 18-64Y Group | Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) | 225 Subjects |
| Placebo 18-64Y Group | Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) | 1 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) | 60 Subjects |
| Placebo >64Y Group | Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) | 0 Subjects |
Secondary
Number of Subjects With A/Indonesia/5/05 Antibody Titers ≥ 1:10
Time frame: At Month 6 (Day 182) post Dose 1
Population: The analysis was based on the ATP cohort for analysis of immunogenicity - Month 6, which included all evaluable subjects (meeting all eligibility criteria, complying with the procedures in the protocol, with no elimination criteria during the study) with a complete set of data concerning immunogenicity primary outcome variables available at Month 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With A/Indonesia/5/05 Antibody Titers ≥ 1:10 | 258 Subjects |
| Placebo 18-64Y Group | Number of Subjects With A/Indonesia/5/05 Antibody Titers ≥ 1:10 | 2 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With A/Indonesia/5/05 Antibody Titers ≥ 1:10 | 77 Subjects |
| Placebo >64Y Group | Number of Subjects With A/Indonesia/5/05 Antibody Titers ≥ 1:10 | 1 Subjects |
Secondary
Number of Subjects With a Vaccine Response to the Vaccine-homologous Virus and Drift Variant H5N1 Virus, as Assessed by Microneutralization Assays.
Virus antibody response rates were defined as the number of subjects with antibody titers at Day 42 ≥ 4-fold the pre-vaccination antibody titers. The 2 strains assessed were Flu A/Indonesia/5/05 and Flu A/Vietnam/1194/04.
Time frame: At Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2)
Population: The analysis was based on the ATP cohort for analysis of immunogenicity, which included all evaluable subjects (meeting all eligibility criteria, complying with the procedures in the protocol, with no elimination criteria during the study) with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With a Vaccine Response to the Vaccine-homologous Virus and Drift Variant H5N1 Virus, as Assessed by Microneutralization Assays. | A/Indonesia/5/05 | 177 Subjects |
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With a Vaccine Response to the Vaccine-homologous Virus and Drift Variant H5N1 Virus, as Assessed by Microneutralization Assays. | A/Vietnam/1194/04 | 113 Subjects |
| Placebo 18-64Y Group | Number of Subjects With a Vaccine Response to the Vaccine-homologous Virus and Drift Variant H5N1 Virus, as Assessed by Microneutralization Assays. | A/Indonesia/5/05 | 36 Subjects |
| Placebo 18-64Y Group | Number of Subjects With a Vaccine Response to the Vaccine-homologous Virus and Drift Variant H5N1 Virus, as Assessed by Microneutralization Assays. | A/Vietnam/1194/04 | 12 Subjects |
Secondary
Number of Subjects With Serum Reciprocal HI Antibodies Against A/Indonesia/5/2005 Equal to or Above (≥) 1:10
Time frame: At Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2)
Population: The analysis was based on the ATP cohort for analysis of immunogenicity, which included all evaluable subjects (meeting all eligibility criteria, complying with the procedures in the protocol, with no elimination criteria during the study) with a complete set of data concerning immunogenicity primary outcome variables available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Influenza A (H5N1) 18-64Y Group | Number of Subjects With Serum Reciprocal HI Antibodies Against A/Indonesia/5/2005 Equal to or Above (≥) 1:10 | 1391 Subjects |
| Placebo 18-64Y Group | Number of Subjects With Serum Reciprocal HI Antibodies Against A/Indonesia/5/2005 Equal to or Above (≥) 1:10 | 1 Subjects |
| Influenza A (H5N1) >64Y Group | Number of Subjects With Serum Reciprocal HI Antibodies Against A/Indonesia/5/2005 Equal to or Above (≥) 1:10 | 410 Subjects |
| Placebo >64Y Group | Number of Subjects With Serum Reciprocal HI Antibodies Against A/Indonesia/5/2005 Equal to or Above (≥) 1:10 | 1 Subjects |
Secondary
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1) as Assessed by Microneutralization Assays
Titers were expressed as Geometric Mean Titers (GMTs).
Time frame: At Day 0 and Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2)
Population: The analysis was based on the ATP cohort for analysis of immunogenicity, which included all evaluable subjects (meeting all eligibility criteria, complying with the procedures in the protocol, with no elimination criteria during the study) with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Influenza A (H5N1) 18-64Y Group | Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1) as Assessed by Microneutralization Assays | A/Vietnam/1194/04, Day 0 | 29.9 Titers |
| Influenza A (H5N1) 18-64Y Group | Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1) as Assessed by Microneutralization Assays | A/Indonesia/5/05, Day 42 | 1450.6 Titers |
| Influenza A (H5N1) 18-64Y Group | Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1) as Assessed by Microneutralization Assays | A/Vietnam/1194/04, Day 42 | 163.1 Titers |
| Influenza A (H5N1) 18-64Y Group | Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1) as Assessed by Microneutralization Assays | A/Indonesia/5/05, Day 0 | 22.4 Titers |
| Placebo 18-64Y Group | Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1) as Assessed by Microneutralization Assays | A/Indonesia/5/05, Day 42 | 631.1 Titers |
| Placebo 18-64Y Group | Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1) as Assessed by Microneutralization Assays | A/Indonesia/5/05, Day 0 | 52.4 Titers |
| Placebo 18-64Y Group | Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1) as Assessed by Microneutralization Assays | A/Vietnam/1194/04, Day 42 | 213.4 Titers |
| Placebo 18-64Y Group | Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1) as Assessed by Microneutralization Assays | A/Vietnam/1194/04, Day 0 | 94.4 Titers |
Secondary
Titers for Serum HI Antibodies Against A/Indonesia/5/05 (H5N1)
Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was ≥ 1:10.
Time frame: At Month 6 (Day 182) after Dose 1
Population: The analysis was based on the ATP cohort for analysis of immunogenicity - Month 6, which included all evaluable subjects (meeting all eligibility criteria, complying with the procedures in the protocol, with no elimination criteria during the study) with a complete set of data concerning immunogenicity primary outcome variables at Month 6.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Influenza A (H5N1) 18-64Y Group | Titers for Serum HI Antibodies Against A/Indonesia/5/05 (H5N1) | 36.2 Titers |
| Placebo 18-64Y Group | Titers for Serum HI Antibodies Against A/Indonesia/5/05 (H5N1) | 5.5 Titers |
| Influenza A (H5N1) >64Y Group | Titers for Serum HI Antibodies Against A/Indonesia/5/05 (H5N1) | 44.8 Titers |
| Placebo >64Y Group | Titers for Serum HI Antibodies Against A/Indonesia/5/05 (H5N1) | 5.4 Titers |