Immunogenicity and Safety Study of Different Formulations of GlaxoSmithKline (GSK) Biologicals H7N1 Influenza Vaccine Administered to Adults 65 Years of Age and Older

Study Overview
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Brief Summary
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The purpose of this placebo controlled study is to evaluate the safety and immunogenicity of different formulations of GSK Biologicals H7N1 influenza vaccine in subjects 65 years of age and older. The study will evaluate safety related events and antibody immune responses to different formulations of study vaccine.

Official Title
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An Observer-blind Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Influenza Vaccine(s) GSK2789869A Administered in Adults 65 Years of Age and Older

Conditions
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Influenza

Intervention / Treatment
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* Biological: Investigational H7N1 vaccine GSK2789869A
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adults who are 65 years of age and older at the time of first study vaccination. Written informed consent obtained from the subject. Subjects who the investigator believes can and will comply with the requirements of the protocol. Stable health status, as established by medical history and physical exam, and defined by absence of a health event satisfying the definition of a serious adverse event, or a change in an ongoing drug therapy due to therapeutic failure or symptoms of drug toxicity, within 1 month prior to enrollment. Access to a consistent means of telephone contact, which may be either in the home or at the workplace, land line or mobile, but NOT a pay phone or other multiple-user device. Exclusion Criteria: Presence or evidence of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports. Presence or evidence of substance abuse. Diagnosed with cancer, or treatment for cancer within three years. Persons with a history of cancer who are disease-free without treatment for three years or more are eligible. Persons with a history of histologically-confirmed basal cell carcinoma of the skin successfully treated with local excision only are excepted and are eligible, but other histologic types of skin cancer are exclusionary. Women who are disease-free three years or more after treatment for breast cancer and receiving long-term prophylaxis are eligible. Diagnosed with excessive daytime sleepiness (unintended sleep episodes during the day present almost daily for at least one month), or narcolepsy; or history of narcolepsy in subject's parent, sibling or child. Presence of a temperature ≥ 38.0ºC (≥100.4ºF), 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 (HIV) infection. Receipt of systemic glucocorticoids within 30 days prior to the first dose of study vaccine/placebo, or any other cytotoxic, immunosuppressive or immune-modifying drugs within 6 months of first study vaccine/placebo dose. Topical, intra-articularly injected, or inhaled glucocorticoids, topical calcineurin inhibitors or imiquimod are allowed. 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 vaccination are eligible. Persons receiving prophylactic antiplatelet medications, e.g., low-dose aspirin, and without a clinically-apparent bleeding tendency, are eligible. An acute evolving neurological disorder or Guillain Barré Syndrome within 42 days of receipt of prior seasonal or pandemic influenza vaccine. Administration of an inactive vaccine within 14 days or of a live attenuated vaccine within 30 days before the first dose of study vaccine/placebo. Planned administration of any vaccine other than the study vaccine/placebo before blood sampling at the Day 42 visit. Previous administration of any H7 vaccine or physician-confirmed H7 disease. Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine/placebo, or planned use during the study period. Receipt of any immunoglobulins and/or any blood products within 90 days before the first dose of study vaccine/placebo, or planned administration of any of these products during the study period. Any known or suspected allergy to any constituent of influenza vaccines or component used in the manufacturing process of the study vaccine including a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine. Any condition which, in the opinion of the investigator, prevents the subject from participating in the study.

Ages Eligible for Study
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Minimum Age: 65 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2789869A F1 Group<br>Healthy male and female adults, 65 years of age and older, who received two doses of GSK2789869A H7N1 vaccine Formulation 1 (F1), administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and of the dominant arm at Day 21. | Biological: Investigational H7N1 vaccine GSK2789869A<br>* Two doses of GSK2789869A H7N1 vaccine administered intramuscularly to the deltoid region at Day 0 and Day 21.<br>|
| Experimental: GSK2789869A F2 Group<br>Healthy male and female adults, 65 years of age and older, who received two doses of GSK2789869A H7N1 vaccine Formulation 2 (F2), administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and of the dominant arm at Day 21. | Biological: Investigational H7N1 vaccine GSK2789869A<br>* Two doses of GSK2789869A H7N1 vaccine administered intramuscularly to the deltoid region at Day 0 and Day 21.<br>|
| Experimental: GSK2789869A F3 Group<br>Healthy male and female adults, 65 years of age and older, who received two doses of GSK2789869A H7N1 vaccine Formulation 3 (F3), administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and of the dominant arm at Day 21. | Biological: Investigational H7N1 vaccine GSK2789869A<br>* Two doses of GSK2789869A H7N1 vaccine administered intramuscularly to the deltoid region at Day 0 and Day 21.<br>|
| Experimental: GSK2789869A F4 Group<br>Healthy male and female adults, 65 years of age and older, who received two doses of GSK2789869A H7N1 vaccine Formulation 4 (F4), administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and of the dominant arm at Day 21. | Biological: Investigational H7N1 vaccine GSK2789869A<br>* Two doses of GSK2789869A H7N1 vaccine administered intramuscularly to the deltoid region at Day 0 and Day 21.<br>|
| Placebo Comparator: Placebo Group<br>Healthy male and female adults, 65 years of age and older, who received two doses of Placebo, administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and of the dominant arm at Day 21. | Biological: Placebo<br>* Two doses of placebo administered intramuscularly to the deltoid region at Day 0 and Day 21.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted (SCR) Subjects for Hemagglutination Inhibition (HI) Antibodies Against the Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain | Seroconversion was defined as: For initially seronegative subjects [antibody titer below (<) 10 post-vaccination], antibody titer greater than or equal to (≥) 40 after vaccination; For initially seropositive subjects (antibody titer ≥ 10 prior to vaccination), antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. The Flu strain assessed was A/mallard/Netherlands/12/2000 NIBRG-63 (H7N1) (Flu A/mallard/NL/12/2000 H7N1). | At Day 42 | 
| Number of Subjects Who Were Seroprotected for HI Antibodies Against the Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain | A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40, that usually is accepted as indicating protection. | At Day 42 | 
| Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain | GMFR, also known as seroconversion factor (SCR) or mean geometric increase (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 Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest; prevented normal activities as assessed by inability to attend/do work or school. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (symptoms included nausea, vomiting, diarrhoea and/or abdominal pain), headache, joint pain at other location, muscle aches, shivering, sweating and fever [defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination. Grade 3 symptom = general symptom that prevented normal everyday activities as assessed by inability to attend/do work or school, or required intervention of a physician/healthcare provider. Grade 3 fever = temperature > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values | Among analysed biochemical parameters were alanine aminotransferase [ALT], aspartate aminotransferase [AST], basophils [BAS], creatinine [CRE], eosinophils [EOS], hematocrit [HEM], hemoglobin [HgB], lymphocytes [LYM], monocytes [MON], neutrophils [NEU], platelets [PLA], red blood cells [RBC] and white blood cells [WBC]. | At Day 0 | 
| Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values | Among analysed biochemical parameters were alanine aminotransferase [ALT], aspartate aminotransferase [AST], basophils [BAS], creatinine [CRE], eosinophils [EOS], hematocrit [HEM], hemoglobin [HgB], lymphocytes [LYM], monocytes [MON], neutrophils [NEU], platelets [PLA], red blood cells [RBC] and white blood cells [WBC]. | At Day 7 | 
| Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values | Among analysed biochemical parameters were alanine aminotransferase [ALT], aspartate aminotransferase [AST], basophils [BAS], creatinine [CRE], eosinophils [EOS], hematocrit [HEM], hemoglobin [HgB], lymphocytes [LYM], monocytes [MON], neutrophils [NEU], platelets [PLA], red blood cells [RBC] and white blood cells [WBC]. | At Day 21 | 
| Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values | Among analysed biochemical parameters were alanine aminotransferase [ALT], aspartate aminotransferase [AST], basophils [BAS], creatinine [CRE], eosinophils [EOS], hematocrit [HEM], hemoglobin [HgB], lymphocytes [LYM], monocytes [MON], neutrophils [NEU], platelets [PLA], red blood cells [RBC] and white blood cells [WBC]. | At Day 28 | 
| Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values | Among analysed biochemical parameters were alanine aminotransferase [ALT], aspartate aminotransferase [AST], basophils [BAS], creatinine [CRE], eosinophils [EOS], hematocrit [HEM], hemoglobin [HgB], lymphocytes [LYM], monocytes [MON], neutrophils [NEU], platelets [PLA], red blood cells [RBC] and white blood cells [WBC]. | At Day 42 | 
| Number of Subjects With Any Medically-attended Adverse Events (MAEs) | MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any MAE(s) = Occurrence of any MAE(s) regardless of intensity grade or relation to vaccination. | From Day 0 up to Day 42 | 
| Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs) | Any pIMD was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration. | From Day 0 up to Day 42 | 
| 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. | From Day 0 up to Day 42 | 
| Number of Subjects With Serious Adverse Events (SAEs) | 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 up to Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With HI Antibody Concentrations Above the Cut-off Value for Vaccine-homologous (H7N1) | Seropositivity cut-off values assessed were equal to or above (≥) 1:10 in the sera of subjects seronegative before vaccination. The flu strain assessed was Flu A/mallard/NL/12/2000 (H7N1). | At Days 0, 21, 42 and Months 6 and 12 | 
| Titers for Antibodies Against Flu A/Mallard/NL/12/2000 Strain of Influenza Disease Vaccine-homologous (H7N1) | Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strain assessed was Flu A/mallard/NL/12/2000 (H7N1). | At Days 0, 21, 42 and Months 6 and 12 | 
| Number of Seroprotected (SPR) Subjects Against HI Antibodies for Vaccine-homologous (H7N1) | Seroprotection (SPR) was defined as the proportion of subjects with H7N1 reciprocal HI titers equal to or above (≥) 1:40 against the tested vaccine virus. The flu strain assessed was Flu A/mallard/NL/12/2000 (H7N1). | At Days 0, 21 and 42 and at Months 6 and 12 | 
| Number of Seroconverted (SCR) Subjects for HI Antibodies for Vaccine-homologous (H7N1) | SCR was defined as the proportion of subjects who had either a pre-vaccination reciprocal HI titer < 10 and a post-vaccination reciprocal titer ≥ 40, or a pre-vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post-vaccination reciprocal titer against the vaccine virus. The flu strain assessed was Flu A/mallard/NL/12/2000 (H7N1). | At Days 21 and 42 and at Months 6 and 12 | 
| Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/Mallard/NL/12/2000 Strain of Influenza Disease Vaccine-homologous (H7N1) | GMFR, also known as seroconversion factor (SCF), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. The flu strain assessed was Flu A/mallard/NL/12/2000 (H7N1). | At Days 21 and 42 and at Months 6 and 12 | 
| Number of Subjects With HI Antibody Concentrations Above the Cut-off Value for Vaccine-heterologous (H7N9) | Seropositivity cut-off values assessed were equal to or above (≥) 1:10 in the sera of subjects seronegative before vaccination. The flu strain assessed was Flu A/Shanghai/2/2013 (H7N9). | At Days 0, 21 and 42 and at Months 6 and 12 | 
| Titers for Antibodies Against Flu A/Shanghai/2/2013 Strain of Influenza Disease Vaccine-heterologous (H7N9) | Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strain assessed was Flu A/Shanghai/2/2013 (H7N9). | At Days 0, 21 and 42 and at Months 6 and 12 | 
| Number of Seroprotected (SPR) Subjects Against HI Antibodies for Vaccine-heterologous (H7N9) | Seroprotection (SPR) was defined as the proportion of subjects with H7N9 reciprocal HI titers equal to or above (≥) 1:40 against the tested vaccine virus. The flu strain assessed was Flu A/Shanghai/2/2013 (H7N9). | At Days 0, 21 and 42 and at Months 6 and 12 | 
| Number of Seroconverted (SCR) Subjects for HI Antibodies for Vaccine-heterologous (H7N9) | SCR was defined as the proportion of subjects who had either a pre-vaccination reciprocal HI titer < 10 and a post-vaccination reciprocal titer ≥ 40, or a pre-vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post-vaccination reciprocal titer against the vaccine virus. The flu strain assessed was Flu A/Shanghai/2/2013 (H7N9). | At Days 21 and 42 and at Months 6 and 12 | 
| Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/Shanghai/2/2013 Strain of Influenza Disease Vaccine-heterologous (H7N9) | GMFR, also known as seroconversion factor (SCF), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. The flu strain assessed was Flu A/Shanghai/2/2013 (H7N9). | At Days 21 and 42 and at Months 6 and 12 | 
| Number of Subjects With HI Neutralizing Antibody Concentrations Above the Cut-off Value for Vaccine-homologous (H7N1) | Seropositivity cut-off values assessed were equal to or above (≥) 1:28 in the sera of subjects seronegative before vaccination. The flu strain assessed was Flu A/mallard/NL/12/2000 (H7N1). | At Days 0, 21 and 42 and Month 6 | 
| Titers for Serum Neutralizing Antibodies Against Flu A/Mallard/NL/12/2000 Strain of Influenza Disease Vaccine-homologous (H7N1) | Titers are presented as geometric mean titers (GMTs). The flu strain assessed was Flu A/mallard/NL/12/2000. The reference seropositivity cut-off value was ≥ 1:28. | At Days 0, 21 and 42 and at Month 6 | 
| Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Against the Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain | Vaccine response was defined as: For initially seronegative subjects antibody titer ≥ 1:56 at post-vaccination]; For initially seropositive subjects antibody titer at post-vaccination ≥ 4 fold the pre-vaccination antibody titer. The Flu strain assessed was Flu A/mallard/NL/12/2000 (H7N1). | At Days 21 and 42 and at Month 6 | 
| Number of Subjects With HI Neutralizing Antibody Concentrations Above the Cut-off Value for Vaccine-heterologous (H7N9) | Seropositivity cut-off values assessed were equal to or above (≥) 1:28 in the sera of subjects seronegative before vaccination. The flu strain assessed was Flu A/Anhui/1/2013 (H7N9). | At Days 0, 21 and 42 and at Month 6 | 
| Titers for Antibodies Against Flu A/Anhui/1/2013 Strain of Influenza Disease Vaccine-homologous (H7N9) | Titers are presented as geometric mean titers (GMTs). The flu strain assessed was Flu A/Anhui/1/2013. The reference seropositivity cut-off value was ≥ 1:28. | At Days 0, 21 and 42 and at Month 6 | 
| Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Against the Flu A/Anhui/1/2013 (H7N9) Virus Strain | Vaccine response was defined as: For initially seronegative subjects antibody titer ≥ 1:56 at post-vaccination]; For initially seropositive subjects antibody titer at post-vaccination ≥ 4 fold the pre-vaccination antibody titer. The Flu strain assessed was Flu A/Anhui/1/2013 (H7N9). | At Days 21 and 42 and at Month 6 | 
| Number of Subjects With Any Medically-attended Adverse Events (MAEs) | MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any MAE(s) = Occurrence of any MAE(s) regardless of intensity grade or relation to vaccination. Analysis of intensity and relationship to vaccination of MAEs was not performed. | From Day 42 up to Month 12 | 
| Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs) | An pIMD was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration. | From Day 42 up to Month 12 | 
| 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 the 21-day (From Day 0 to Day 20) post-vaccination period after each dose | 
| Number of Subjects With Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | During the entire study period (From Day 0 up to Month 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H7N1, AS03 adjuvant, Safety, Immunogenicity, Influenza, Adults, Elderly adults