Study to Evaluate Immunogenicity and Safety of an Investigational Influenza Vaccine (H1N1) in Adults

Study Overview
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Brief Summary
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The objective of the study is to evaluate the immunogenicity and safety of GSK Biologicals' investigational vaccine GSK2340272A.

Official Title
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Safety and Immunogenicity Study of GSK Biologicals' Influenza Vaccine GSK2340272A in Adults Aged 18 Years and Above

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK investigational vaccine GSK2340272A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female aged 18 years or above at the time of the first vaccination. Subjects who the investigator believes that they can and will comply with the requirements of the protocol. Written informed consent obtained from the subject. Satisfactory baseline medical assessment by history and physical examination. Stable health status is defined as the 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 one month prior to enrolment. 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. 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 during the entire treatment period and for 2 months after completion of the vaccination series. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of the study vaccine or planned use during the study period. Potential subjects in the follow-up phase of a prior investigational study may be enrolled if the investigator's judgment is that it will have no effect on safety, reactogenicity, or immunogenicity endpoints in this study, and that it does not violate the protocol requirements of the prior trial. Presence of evidence of substance abuse or 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 of an axillary temperature >= 37.5ºC, or acute symptoms greater than mild severity on the scheduled date of first vaccination. NOTE: The subject may be vaccinated at a later date, provided symptoms have resolved, vaccination occurs within the window specified by the protocol, and all other eligibility criteria continue to be satisfied. Diagnosed with cancer, or treatment for cancer, within the past 3 years. Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible. Persons with a history of histological-confirmed basal cell carcinoma of the skin successfully treated with local excision only are excepted and may enrol within 3 years of diagnosis, but other histological types of skin cancer require a 3-year untreated and disease-free window as above. Women who are disease-free 3 years or more after treatment for breast cancer and receiving long-term prophylactic hormonal therapy are excepted and may enrol. Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection. Chronic administration of immunosuppressants or other immune modifying drugs within 6 months of study enrolment or planned administration during the study period. Receipt of any immunoglobulins and/or any blood products within 3 months of study enrolment 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 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 history of Guillain-Barré syndrome. Clinically or virologically confirmed influenza infection within 6 months preceding the study start. Administration of any vaccines within 30 days before vaccination. Any known or suspected allergy to any constituent of influenza vaccines; anaphylactic-type reaction to any constituent of influenza vaccines; or a history of severe adverse reaction to a previous influenza vaccine. Pregnant or lactating female Female planning to become pregnant or planning to discontinue contraceptive precautions. Any conditions which, in the opinion of the investigator, prevents the subjects from participating in the study.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2340272A 2D Group<br>Healthy male or female adults, aged 18 to 60 years (18-60y) and above (>60y), who received two doses (2D) of GSK2340272A vaccine, one administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and the other one, administered intramuscularly in the deltoid region of the dominant arm at Day 21. | Biological: GSK investigational vaccine GSK2340272A<br>* One or two intramuscular injections in the deltoid region of the non-dominant or the dominant arm.<br>|
| Experimental: GSK2340272A 1D Group<br>Healthy male or female adults, aged 18 to 60 years (18-60y) and above (>60y), who received a single dose (1D) of GSK2340272A vaccine, administered intramuscularly in the deltoid region of the non-dominant arm at Day 0. | Biological: GSK investigational vaccine GSK2340272A<br>* One or two intramuscular injections in the deltoid region of the non-dominant or the dominant arm.<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 | 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/California/7/2009 (H1N1)v-like influenza (Flu A/CAL/7/09). This outcome included only subjects who received two doses of the study product and results were tabulated per age stratum. The CHMP criterion was fulfilled if the post-vaccination point estimate for SPR was > 70% in subjects 18 to 60 of age or > 60% for subjects above 60 years of age . | At Day 21 | 
| Number of Subjects Who Were Seroprotected (SPR) for HI Antibodies Against the Flu A/California/7/2009 (H1N1) 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. This outcome included only subjects who received two doses of the study product and the results were tabulated per age stratum. The CHMP criterion was fulfilled if the post-vaccination point estimate for SPR was > 70% in subjects 18 to 60 of age or > 60% for subjects above 60 years of age . | At Day 21 | 
| Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease | GMFR was defined as the fold change in serum HI geometric mean titers (GMTs) post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/CAL/7/09. This outcome included only subjects who received two doses of the study product and results were tabulated per age stratum. The CHMP criterion was fulfilled if the point estimated for GMFR was > 2.5 in subjects 18 to 60 years old or > 2 for subjects > 60 years of age. | At Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Were Seropositive for HI Antibodies Against the Flu A/California/7/2009 (H1N1) Virus Strain | A seropositive subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:10, that usually is accepted as indicating protection. The results for this assay were tabulated per age stratum. | At Days 0, 21 and 42 | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease | Titers are presented as geometric mean titers (GMTs). The flu strain assessed was Flu A/CAL/7/09. The reference seropositivity cut-off value was ≥ 1:10. The results for this assay were tabulated per age stratum. | At Days 0, 21 and 42 | 
| Number of Subjects Who Were Seropositive for HI Antibodies Against the Flu A/California/7/2009 (H1N1) Virus Strain | A seropositive subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:10, that usually is accepted as indicating protection. The results for this assay were tabulated per age stratum. | At Day 182 and 364 | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease | Titers are presented as geometric mean titers (GMTs). The flu strain assessed was Flu A/CAL/7/09. The reference seropositivity cut-off value was ≥ 1:10. The results for this assay were tabulated per age stratum. | At Day 182 and 364 | 
| Number of Seroconverted (SCR) Subjects for Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/2009 Strain of Influenza Disease | Seroconversion was defined as: For initially seronegative subjects [antibody titer below (<) 10 post to 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/California/7/2009 (H1N1)v-like influenza (Flu A/CAL/7/09). This outcome included only subjects who received one dose of the study product and the results were tabulated per age stratum. The CHMP criterion was fulfilled if the post-vaccination point estimate for SPR was > 70% in subjects 18 to 60 of age or > 60% for subjects above 60 years of age . | At Days 21 and 42 | 
| Number of Seroconverted (SCR) Subjects for Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease | Seroconversion was defined as: For initially seronegative subjects [antibody titer below (<) 10 post to 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/California/7/2009 (H1N1)v-like influenza (Flu A/CAL/7/09). The results for this assay were tabulated per age stratum. The CHMP criterion was fulfilled if the post-vaccination point estimate for SPR was > 70% in subjects 18 to 60 of age or > 60% for subjects above 60 years of age . | At Days 182 and 364 | 
| Number of Subjects Who Were Seroprotected (SPR ) for HI Antibodies Against the Flu A/California/7/2009 (H1N1) 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. This outcome included only subjects who received one dose of the study product and the results were tabulated per age stratum. The CHMP criterion was fulfilled if the post-vaccination point estimate for SPR was > 70% in subjects 18 to 60 of age or > 60% for subjects above 60 years of age . | At Days 0, 21 and 42 | 
| Number of Subjects Who Were Seroprotected (SPR ) for HI Antibodies Against the Flu A/California/7/2009 (H1N1) 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. The results for this assay were tabulated per age stratum. The CHMP criterion was fulfilled if the post-vaccination point estimate for SPR was > 70% in subjects 18 to 60 of age or > 60% for subjects above 60 years of age. | At Days 182 and 364 | 
| Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease | GMFR was defined as the fold change in serum HI geometric mean titers (GMTs) post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/CAL/7/09. This outcome included only subjects who received one dose of the study product and the results were tabulated per age stratum. The CHMP criterion was fulfilled if the point estimated for GMFR was > 2.5 in subjects 18 to 60 years old or > 2 for subjects > 60 years of age. | At Days 21 and 42 | 
| Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease | GMFR was defined as the fold change in serum HI geometric mean titers (GMTs) post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/CAL/7/09. The results for this assay were tabulated per age stratum. The CHMP criterion was fulfilled if the point estimated for GMFR was > 2.5 in subjects 18 to 60 years old or > 2 for subjects > 60 years of age. | At Day 182 and 364 | 
| Number of Seropositive Subjects for Serum Neutralizing Antibodies Against Flu A/Netherlands (Neth)/602/09 | A seropositive subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:8, that usually is accepted as indicating protection. The Flu strain assessed was Flu A/Neth/602/09. The results for this assay were tabulated per age stratum. | At Days 0, 21, 42 and 182 | 
| Titers for Serum Neutralizing Antibodies Against Flu A/Neth/602/09 Strain of Influenza Disease | Titers are presented as geometric mean titers (GMTs). The flu strain assessed was Flu A/Neth/602/09. The reference seropositivity cut-off value was ≥ 1:8. The results for this assay were tabulated per age stratum. | At Days 0, 21, 42 and 182 | 
| Number of Seroconverted Subjects for Serum Neutralizing Antibodies Against Flu A/Neth/602/09 | Seroconversion was defined as: For initially seronegative subjects, antibody titer ≥ 1:8 after vaccination; For initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. The Flu strain assessed was Flu A/Neth/602/09. The results were tabulated per age stratum. | At Days 21, 42 and 182 | 
| 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 = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. This outcome included all the subjects who received 1 dose of the study product and the assay results were tabulated per age stratum. | During the 7-day (Days 0-6) post-dose 1 vaccination period | 
| Number of Days With Solicited Local Symptoms | The number of days with any solicited local symptoms reported during the solicited post-vaccination period. This outcome included all the subjects who received 1 dose of the study product and the assay results were tabulated per age stratum. | During the 7-day (Days 0-6) post-dose 1 vaccination period | 
| 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 = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. This outcome included only subjects who received two doses of the study product and the results were tabulated per age stratum. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Days With Solicited Local Symptoms | The number of days with any solicited local symptoms reported during the solicited post-vaccination period. This outcome included only subjects who received 2 doses of the study product and the results were tabulated per age stratum. No subjects from GSK2340272A 2D (18-60y) Sub-Group presented any redness post dose 1. | 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, headache, joint pain at other location, muscle aches, shivering, sweating and fever [defined as axillary temperature equal to or above (>) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = temperature ≥ 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. This outcome included all the subjects who received 1 dose of the study product and the assay results were tabulated per age stratum. | During the 7-day (Days 0-6) post-dose 1 vaccination period | 
| Number of Days With Solicited General Symptoms | The number of days with any solicited general symptoms reported during the solicited post-vaccination period. This outcome included all the subjects who received 1 dose of the study product and the results were tabulated per age stratum. | During the 7-day (Days 0-6) post-dose 1 vaccination period | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, headache, joint pain at other location, muscle aches, shivering, sweating and fever [defined as axillary temperature above (>) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = temperature ≥ 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. This outcome inlcuded only subjects who received two doses of the study product and the results were tabulated per age stratum. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Days With Solicited General Symptoms | The number of days with any solicited general symptoms reported during the solicited post-vaccination period. This outcome included only subjects who received two doses of the study product and the results were tabulated per age stratum. No subjects from GSK2340272A 2D (>60y) Sub-Group reported any temperature. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Subjects With Adverse Events of Specific Interest (AESIs) | An AESI was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration. The results were tabulated per age stratum. | During the entire study period (from Day 0 up to Day 364) | 
| Number of Subjects With Normal/Abnormal Biochemical and Haematological Levels | Among biochemical and haematological parameters assessed were alanine aminotransferase [ALT], alkaline phosphatase [AP], aspartate aminotransferase [AST], total bilirubin [BIL], creatinine [CRE], blood urea nitrogen [BUN]. Levels of haematological/biochemical parameters assessed with respect to normal laboratory values were - unknown, below, within and above in subjects aged 18-60 years and > 60 years old. | At Days 0, 21, 42, 182 and 364 | 
| Number of Subjects With Any, Grade 3 and Related 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. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. This outcome included all the subjects who received 1 dose of the study product and the results were tabulated per age stratum. | Within 21 days after the first vaccination (Day 0 - Day 20) | 
| Number of Subjects With Any, Grade 3 and Related 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. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. The results were tabulated per age stratum. | Within 84 days after the first vaccination and 63 days after the second vaccination (Day 0 - Day 83) | 
| 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. The results were tabulated per age stratum. | During the entire study period (from Day 0 up to Day 364) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza infection, GSK Bio's influenza vaccine GSK2340272A