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

Study Overview
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Brief Summary
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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.

Official Title
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A Trial to Evaluate the Safety and Immunogenicity of an Investigational Vaccination Regimen in Adults Aged ≥18 Years

Conditions
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Influenza

Intervention / Treatment
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* Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Influenza A (H5N1) 18-64Y Group<br>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. | Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted<br>* Two intramuscular injections at Days 0 and 21.<br>|
| Placebo Comparator: Placebo 18-64Y Group<br>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. | Biological: Placebo<br>* Two intramuscular injections at Days 0 and 21.<br>|
| Experimental: Influenza A (H5N1) >64Y Group<br>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. | Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted<br>* Two intramuscular injections at Days 0 and 21.<br>|
| Placebo Comparator: Placebo >64Y Group<br>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. | Biological: Placebo<br>* Two intramuscular injections at Days 0 and 21.<br>|
| Experimental: Influenza A (H5N1) Group<br>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. | Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted<br>* Two intramuscular injections at Days 0 and 21.<br>|
| Placebo Comparator: Placebo Group<br>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. | Biological: Placebo<br>* Two intramuscular injections at Days 0 and 21.<br>|
| Experimental: Influenza A (H5N1) 18-60Y Group<br>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. | Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted<br>* Two intramuscular injections at Days 0 and 21.<br>|
| Placebo Comparator: Placebo 18-60Y Group<br>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. | Biological: Placebo<br>* Two intramuscular injections at Days 0 and 21.<br>|
| Experimental: Influenza A (H5N1) >60Y Group<br>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. | Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted<br>* Two intramuscular injections at Days 0 and 21.<br>|
| Placebo Comparator: Placebo >60Y Group<br>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. | Biological: Placebo<br>* Two intramuscular injections at Days 0 and 21.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2) | 
| 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. | At Day 0 and Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2) | 
| 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. | During a 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after each vaccine administration | 
| 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. | During a 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after each vaccine administration | 
| 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. | During a 21-day follow-up period for each vaccine administration, as well as overall (Day 0 through Day 84) | 
| 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. | From Day 0 through Day 182 and through Day 379. | 
| Number of Subjects With Medically Attended Events (MAEs) |  | From Day 0 through Day 182 and through Day 364. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | At Month 6 (Day 182) after 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) | Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was ≥ 1:10. | At Month 6 (Day 182) after Dose 1 | 
| 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. | At Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2) | 
| 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). | At Day 0 and Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccines, immunogenicity, human, safety, influenza