Immunogenicity & Safety of GSK's Influenza Vaccine 1557484A Given to Adults Aged ≥18 Years

Phase 3

Completed

Conditions: Influenza

Interventions: Biological: Placebo
Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted

Registration Number: NCT00616928

Lead Sponsor: GlaxoSmithKline

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 4561

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo >64Y Group	Placebo	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.
Placebo 18-64Y Group	Placebo	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.
Placebo Group	Placebo	Pooled group of subjects aged \>18 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.
Influenza A (H5N1) Group	Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted	Pooled group of subjects aged \>18 years, who received 2 doses of the Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted vaccine 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.
Placebo 18-60Y Group	Placebo	Subjects aged 18-60 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.
Influenza A (H5N1) >60Y Group	Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted	Subjects aged \>60 years, who received 2 doses of the Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted vaccine 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.
Influenza A (H5N1) 18-64Y Group	Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted	Subjects aged 18-64 years, who received 2 doses of the Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted vaccine 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.
Influenza A (H5N1) >64Y Group	Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted	Subjects aged \> 64 years, who received 2 doses of the Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted vaccine 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.
Influenza A (H5N1) 18-60Y Group	Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted	Subjects aged 18-60 years, who received 2 doses of the Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted vaccine 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.
Placebo >60Y Group	Placebo	Subjects aged \> 60 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.

Primary Outcome Measures

Name	Time	Method
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 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.
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 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.

Secondary Outcome Measures

Name	Time	Method
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 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).
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 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.