Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Monovalent Pandemic H5N1 Vaccine in Adults

Study Overview
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Brief Summary
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This trial will assess the immunogenicity and safety of GSK Biologicals' vaccine GSK1557484A, prepared from old concentrated monobulk material, in adults aged 18 to 64 years, when administered up to 5 years following production.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Monovalent Pandemic H5N1 Vaccine 1557484A in Adults Aged 18 - 64 Years

Conditions
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Influenza

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes can and will comply with the requirements of the protocol. A male or female 18 to 64 years of age at the time of the first vaccination. Written informed consent obtained from the subject. Stable general health as established by medical history and clinical examination before entering into the study. Subject access to a consistent means of telephone contact, land line or mobile, but NOT a pay phone or other multiple-user device. Female subjects of non-childbearing potential may be enrolled in the study. Female subjects of childbearing potential may be enrolled in the study, if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception for 2 months after completion of the vaccination series. Exclusion Criteria: Previous vaccination at any time with an H5N1 vaccine. Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period. Presence of significant acute or chronic, uncontrolled medical or psychiatric illness. Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, even if stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports. Presence of a temperature ≥ 38.0ºC, or acute symptoms greater than mild severity on the scheduled date of first dose. Diagnosed with cancer, or treatment for cancer, within 3 years. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Receipt of systemic glucocorticoids within 1 month prior to study enrolment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrolment. Topical, intra-articularly injected, or inhaled glucocorticoids, topical calcineurin inhibitors or imiquimod are allowed. Receipt of any immunoglobulins and/or any blood products within 3 months before first study vaccination or planned administration of any of these products during the study period. Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. Persons receiving individual doses of low molecular weight heparin outside of 24 hours prior to dosing, are eligible. Persons receiving prophylactic antiplatelet medications, and without a clinically-apparent bleeding tendency, are eligible. An acute evolving neurological disorder or history of Guillain-Barré syndrome within 6 weeks of receipt of seasonal influenza vaccine. Administration of an inactivated or a live, attenuated seasonal influenza vaccine within 14 days before the first study vaccine dose, or of any other vaccine(s) not foreseen by the study protocol within 30 days before the first study vaccine dose. Planned administration of any vaccine(s) not foreseen by the study protocol through completion of the Day 42 visit. Any known or suspected allergy to any constituent of influenza vaccines, or history of severe reaction to a previous influenza vaccination. Known pregnancy or a positive urine beta-human chorionic gonadotropin test result prior to the first study vaccine dose. Lactating or nursing women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Influenza A (H5N1) Group<br>Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of the Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted, at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm. | Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted<br>* Intramuscular (IM), two doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects Against the H5N1 Strain of Influenza Disease. | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination reciprocal HI titer less than (<) 1:10 and a post-vaccination reciprocal HI titer greater than or equal to (≥) 1:40 or a pre-vaccination reciprocal HI titer ≥ 1:10 and at least a four-fold increase in post-vaccination reciprocal titer against the vaccine virus. | At Day 42 | 
| Mean Geometric Increase (MGI) for the H5N1 Strain of Influenza Disease. | MGI was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer for the vaccine virus. | At Day 42 | 
| Number of Seroprotected Subjects Against the H5N1 Strain of Influenza Disease. | A seroprotected subject was defined as a vaccinated subject who had H5N1 reciprocal HI titers ≥ 1:40 against the vaccine-homologous virus. | At Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects Against the H5N1 Strain of Influenza Disease. | A seropositive subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:10. | At Day 0 and Day 42 | 
| Titers for Serum HI Antibodies Against the H5N1 Strain of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). | At Day 0 and Day 42 | 
| Number of Seropositive Subjects Against the H5N1 Strain of Influenza Disease. | A seropositive subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:10. | At Day 0 and Day 182 | 
| Titers for Serum HI Antibodies Against the H5N1 Strain of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). | At Day 0 and Day 182 | 
| Number of Seroprotected Subjects Against the H5N1 Strain of Influenza Disease. | A seroprotected subject was defined as a vaccinated subject who had H5N1 reciprocal HI titers ≥ 1:40 against the vaccine-homologous virus. | At Day 0 and Day 182 | 
| Number of Seroconverted Subjects Against the H5N1 Strain of Influenza Disease. | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination reciprocal HI titer < 1:10 and a post-vaccination reciprocal HI titer (≥) 1:40 or a pre-vaccination reciprocal HI titer ≥ 1:10 and at least a four-fold increase in post-vaccination reciprocal titer against the vaccine virus. | At Day 182 | 
| Mean Geometric Increase (MGI) for the H5N1 Strain of Influenza Disease. | MGI was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer for the vaccine virus. | At Day 182 | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any solicited local symptoms regardless of intensity grade. Grade 3 pain = significant pain at rest; prevented normal activities. Grade 3 Redness/Swelling = Redness/Swelling >100 millimeters (mm). | During the 7-day follow-up period (Days 0-6) after any vaccination | 
| Duration of Solicited Local Symptoms After Vaccination. | Assessed solicited local symptoms were pain, redness and swelling. Duration was defined as the number of days with any grade of local symptoms. | During the 7-day (Days 0-6) post-vaccination period following each dose | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal, headache, joint pain at other location (joint pain), muscle aches, shivering, sweating and fever. Any = occurrence of any solicited general symptoms regardless of intensity grade or relationship to vaccination. Any fever was defined as axillary temperature ≥ 38 degrees Celsius (°C). Grade 3 = general symptom that prevented normal activities. Grade 3 fever = fever ≥ 39.0°C. Related = general symptom assessed by the investigator as causally related to the vaccination. | During the 7-day follow-up period (Days 0-6) after any vaccination | 
| Duration of Solicited General Symptoms After Vaccination. | Assessed solicited general symptoms were fatigue, gastrointestinal, headache, joint pain at other location (joint pain), muscle aches, increased sweating and shivering. Duration was defined as the number of days with any grade of general symptoms. | During the 7-day (Days 0-6) post-vaccination period following each dose | 
| Number of Subjects With Any, Grade 3 and Related Medically Attended Adverse Events (MAEs). | MAE was defined as any unsolicited symptom that received medical attention such as hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any = occurrence of any MAEs regardless of intensity grade or relationship to vaccination. Grade 3 = event which prevented normal activities Related = event assessed by the investigator as causally related to the study vaccination. | From Day 0 to Day 84 | 
| Number of Subjects With Any, Grade 3 and Related Medically Attended Adverse Events (MAEs). | MAE was defined as any unsolicited symptom that received medical attention such as hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel for any reason. Any = occurrence of any MAEs regardless of intensity grade or relationship to vaccination. Grade 3 = event which prevented normal activities. Related = event assessed by the investigator as causally related to the study vaccination. | From Day 0 to Day 385 | 
| Number of Subjects With Potential Immune Mediated Disease (s) (pIMDs). | pIMDs are a subset of AEs that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune aetiology. | From Day 0 to Day 84 and from Day 0 to Day 385 | 
| Number of Subjects With Normal and Abnormal Biochemical and Haematological Parameters. | Assessed biochemical and haematological parameters were alanine aminotransferase (ALT), aspartate aminotransferase (AST), basophils (BAS), blood urea nitrogen (BUN), creatinine (CREA), eosinophils (EOS), haematocrit (HCRIT), haemoglobin (HBIN), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), white blood cells (WBC), total bilirubin (Total BIR), bilirubin conjugated/direct (BIL con/dir). Per parameter, it was assessed whether subjects had laboratory values unknown, below, within or above the normal ranges. This outcome presents BAS, EOS and HCRIT results. | At Day 0 and Day 42 | 
| Number of Subjects With Normal and Abnormal Biochemical and Haematological Parameters. | Assessed biochemical and haematological parameters were alanine aminotransferase (ALT), aspartate aminotransferase (AST), basophils (BAS), blood urea nitrogen (BUN), creatinine (CREA), eosinophils (EOS), haematocrit (HCRIT), haemoglobin (HBIN), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), white blood cells (WBC), total bilirubin (Total BIR), bilirubin conjugated/direct (BIL con/dir). Per parameter, it was assessed whether subjects had laboratory values unknown, below, within or above the normal ranges. This outcome presents HBIN, LYM and MON results. | At Day 0 and Day 42 | 
| Number of Subjects With Normal and Abnormal Biochemical and Haematological Parameters. | Assessed biochemical and haematological parameters were alanine aminotransferase (ALT), aspartate aminotransferase (AST), basophils (BAS), blood urea nitrogen (BUN), creatinine (CREA), eosinophils (EOS), haematocrit (HCRIT), haemoglobin (HBIN), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), white blood cells (WBC), total bilirubin (Total BIR), bilirubin conjugated/direct (BIL con/dir). Per parameter, it was assessed whether subjects had laboratory values unknown, below, within or above the normal ranges. This outcome presents NEU, PLA and RBC results. | At Day 0 and Day 42 | 
| Number of Subjects With Normal and Abnormal Biochemical and Haematological Parameters. | Assessed biochemical and haematological parameters were alanine aminotransferase (ALT), aspartate aminotransferase (AST), basophils (BAS), blood urea nitrogen (BUN), creatinine (CREA), eosinophils (EOS), haematocrit (HCRIT), haemoglobin (HBIN), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), white blood cells (WBC), total bilirubin (Total BIR), bilirubin conjugated/direct (BIL con/dir). Per parameter, it was assessed whether subjects had laboratory values unknown, below, within or above the normal ranges. This outcome presents WBC, ALT and AST results. | At Day 0 and Day 42 | 
| Number of Subjects With Normal and Abnormal Biochemical and Haematological Parameters. | Assessed biochemical and haematological parameters were alanine aminotransferase (ALT), aspartate aminotransferase (AST), basophils (BAS), blood urea nitrogen (BUN), creatinine (CREA), eosinophils (EOS), haematocrit (HCRIT), haemoglobin (HBIN), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), white blood cells (WBC), total bilirubin (Total BIL), bilirubin conjugated/direct (BIL con/dir). Per parameter, it was assessed whether subjects had laboratory values unknown, below, within or above the normal ranges. This outcome presents Total BIL, BIL con/dir, CREA and BUN results. | At Day 0 and Day 42 | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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 = occurrence of an unsolicited AE regardless of intensity grade or relationship to vaccination. Grade 3 = event which prevented normal activities. Related = event assessed by the investigator as causally related to the study vaccination. | From Day 0 to Day 20 and from Day 0 to Day 84. | 
| Number of Subjects With Any and Related Serious Adverse Events (SAEs) | A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or resulted in a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination. | From Day 0 to Day 84 and from Day 0 to Day 385 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H5N1, Influenza vaccine, influenza infection, GSK1557484A