Safety, Immunogenicity, and Relative Efficacy of H1N1 Vaccines in Adults Aged 18 Years and Older

Study Overview
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Brief Summary
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The purpose of this study is to characterize the safety, immunogenicity, and relative efficacy of the H1N1 (swine) flu vaccines GSK2340273A and GSK2340274A in adults 18 years of age or older.

Detailed Description
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Collaborators: United States Department of Health and Human Services, Office of Biomedical Advanced Research and Development Authority

Official Title
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A Study to Evaluate the Safety, Immunogenicity, and Relative Efficacy of A/California/7/2009 (H1N1)V-like Vaccines GSK2340274A and GSK2340273A in Adults Aged 18 Years and Older

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK2340274A
* Biological: GSK2340273A


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. Written informed consent obtained from the subject. Male and female adults, >= 18 years of age at the time of the first vaccination. Satisfactory baseline medical assessment by history and physical examination. Safety laboratory test results within the parameters specified in the protocol. Comprehension of the study requirements, ability to comprehend and comply with procedures for collection of safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits as demonstrated by signature on the informed consent document. 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 first 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: Medical history of physician-confirmed infection with an A/California/7/2009 (H1N1)v-like virus. Previous vaccination at any time with an A/California/7/2009 (H1N1)v-like virus vaccine. With the exception of seasonal influenza vaccination, administration of any vaccine(s) within 30 days before study vaccination on Day 0. Seasonal influenza vaccine may be administered up to 14 days prior to study vaccination on Day 0. Planned administration of any vaccine other than the study vaccines between Day 0 and the phlebotomy 21 days after vaccination. Planned administration of any monovalent pandemic (H1N1)v-like vaccine other than the study vaccines during the whole study (Day 0 - Day 385). Previous vaccination with an H1N1v-like virus vaccine or a medical history of physician-confirmed infection with an H1N1v-like virus. 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 a temperature >= 38.0ºC (>= 100.4 ºF), oral temperature assessment preferred, or acute symptoms greater than mild severity on the scheduled date of first vaccination. 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 1month prior to study enrollment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrollment. 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 of study enrollment 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 are eligible if no such doses are given in the 24 hours before a study vaccination. Persons receiving prophylactic antiplatelet medications, e.g., low-dose acetylsalicylic acid, and without a clinically-apparent bleeding tendency, are eligible. History of an acute evolving neurological disorder or history of Guillain-Barré syndrome within 6 weeks of receipt of seasonal influenza vaccine. With the exception of seasonal influenza vaccination, administration of any vaccines within 30 days before study vaccination on Day 0. Seasonal influenza vaccine may be administered up to 14 days prior to study vaccination on Day 0. Planned administration of any vaccine other than the study vaccine between Day 0 and the phlebotomy 21 days after the second study vaccine dose. Use of any investigational or non-registered product within 30 days preceding the first dose of study vaccine, or planned use during the study period. Any known or suspected allergy to any constituent of influenza vaccines; a history of anaphylactic-type reaction to any constituent of influenza vaccines; 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 vaccination. Lactating or nursing women.

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: GSK2340274A Group<br>Healthy male or female subjects between and including 18 to 60 years of age and older (>60 years) and between 18 to 64 years of age and older (>64 years), who received one dose of the adjuvanted GSK2340274A vaccine at Day 0, administered intramuscularly into the deltoid region of the non-dominant arm. | Biological: GSK2340274A<br>* One intramuscular injection<br>|
| Experimental: GSK2340273A Group<br>Healthy male or female subjects between and including 18 to 60 years of age and older (>60 years) and between 18 to 64 years of age and older (>64 years), who received one dose of the unadjuvanted GSK2340273A vaccine at Day 0, administered intramuscularly into the deltoid region of the non-dominant arm. | Biological: GSK2340273A<br>* One intramuscular injection<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 Flu A/CAL/7/09 H1N1 Virus Strain | A seroconverted subject was defined as a vaccinated subject who had a post-vaccination titer higher than or equal to (≥)1:40 or at least a 4-fold increase of the pre-vaccination titer of ≥ 1:10. The Flu strain assessed was A/California/7/09 (H1N1)v-like (Flu A/CAL/7/09) in subjects of 18-60 years and older and 18-64 years and older, following the Committee for Medicinal Products for Human Use (CHMP) and the Center for Biologics Evaluation and Research (CBER) guidance. | At Day 21 | 
| Number of Seroprotected (SPR) Subjects for HI Antibodies Against the Flu A/CAL/7/09 H1N1 Virus Strain | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) antibody titer ≥ 1:40 against the tested virus. The Flu strain assessed was A/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09) in subjects 18-60 years and older and 18-64 years and older, following the CHMP and the CBER guidance. | At Day 0 | 
| Number of Seroprotected (SPR) Subjects for HI Antibodies Against the Flu A/CAL/7/09 H1N1 Virus Strain | A seroprotected subject was defined as a vaccinated subject with serum HI antibody titer ≥ 1:40. The Flu strain assessed was A/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09) in subjects 18-60 years and older and 18-64 years and older, following the CHMP and the CBER guidance. | At Day 21 | 
| Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 H1N1 Virus Strain | SCF was defined as the fold increase in serum HI 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, in subjects 18-60 years and older and 18-64 years and older, following the CHMP guidance. | At Day 21 | 
| Number of A/California/7/2009 (H1N1)V-like Illness (ILI) Cases | The analysis focused on Quantitative Reverse Transcription Polymerase Chain Reaction Assay (RT-qPCR)-confirmed A/California/7/2009 (H1N1)v-like illness (ILI) cases. | From Day 14 post-vaccination up to study end (at Day 385) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects for HI Antibodies Against Flu A/CAL/7/09 H1N1 Virus Strain | Cut-off values assessed were greater than or equal to (≥) 1:10 in the sera of subjects seronegative before vaccination. The Flu strains assessed was A/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09) in subjects 18-60 years and older and 18-64 years and older, following the CHMP and the CBER guidance. | At Days 0 and 21 | 
| Titers for Serum HI Antibodies Against Flu A/CAL/7/09 H1N1 Virus Strain | Titers were presented as geometric mean titers (GMTs). The flu strain assessed was /California/7/2009 (H1N1)v-like (Flu A/CAL/7/09) in subjects 18-60 years and older and 18-64 years and older, following the CHMP and the CBER guidance. | At Days 0 and 21 | 
| Number of Seropositive Subjects for HI Antibodies Against Flu A/CAL/7/09 H1N1 Virus Strain | Cut-off values assessed were greater than or equal to (≥) 1:10 in the sera of subjects seronegative before vaccination. The Flu strain assessed was A/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09) in subjects 18-60 years and older and 18-64 years and older, following the CHMP and the CBER guidance. | At Day 42 | 
| Titers for Serum HI Antibodies Against Flu A/CAL/7/09 H1N1 Virus Strain | Titers were presented as geometric mean titers (GMTs). The flu strain assessed was A/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09) in subjects 18-60 years and older and 18-64 years and older, following the CHMP and the CBER guidance. | At Day 42 | 
| Number of Seropositive Subjects for HI Antibodies Against Flu A/CAL/7/09 H1N1 Virus Strain | Cut-off values assessed were greater than or equal to ≥ 1:10 in the sera of subjects seronegative before vaccination. The Flu strain assessed was A/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09) in subjects 18-60 years and older and 18-64 years and older, following the CHMP and the CBER guidance. | At Day 182 | 
| Titers for Serum HI Antibodies Against Flu A/CAL/7/09 H1N1 Virus Strain | Titers were presented as geometric mean titers (GMTs). The flu strain assessed was A/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09) in subjects 18-60 years and older and 18-64 years and older, following the CHMP and the CBER guidance. | At Day 182 | 
| Number of Seroconverted (SCR) Subjects for HI Antibodies Against Flu A/CAL/7/09 H1N1 Virus Strain | A seroconverted subject was defined as a vaccinated subject who had a post-vaccination titer ≥1:40 and at least a 4-fold increase of the pre-vaccination titer. The Flu strain assessed was A/California/7/09 (H1N1)v-like) (Flu A/CAL/7/09) in subjects of 18-60 years and older and 18-64 years and older, following the CHMP and the CBER guidance. | At Day 42 | 
| Number of Seroconverted (SCR) Subjects for HI Antibodies Against Flu A/CAL/7/09 H1N1 Virus Strain | A seroconverted subject was defined as a vaccinated subject who had a post-vaccination titer ≥1:40 and at least a 4-fold increase of the pre-vaccination titer. The Flu strain assessed was A/California/7/09 (H1N1)v-like) (Flu A/CAL/7/09) in subjects of 18-60 years and older and 18-64 years and older, following the CHMP and the CBER guidance. | At Day 182 | 
| Number of Seroprotected (SPR) Subjects for HI Antibodies Against the Flu A/CAL/7/09 H1N1 Virus Strain | A seroprotected subject was defined as a vaccinated subject with serum HI antibody titer ≥ 1:40. The Flu strain assessed was A/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09) in subjects 18-60 years and older and 18-64 years and older, following the CHMP and the CBER guidance. | At Day 42 | 
| Number of Seroprotected (SPR) Subjects for HI Antibodies Against the Flu A/CAL/7/09 H1N1 Virus Strain | A seroprotected subject was defined as a vaccinated subject with serum HI antibody titer ≥ 1:40. The Flu strain assessed was A/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09) in subjects 18-60 years and older and 18-64 years and older, following the CHMP and the CBER guidance. | At Day 182 | 
| Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 H1N1 Virus Strain | SCF was defined as the fold increase in serum HI 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, in subjects 18-60 years and older and 18-64 years and older, following the CHMP. | At Day 42 | 
| Seroconversion Factor (SCF) for HI Antibodies Against A/CAL/7/09 H1N1 Virus Strain | SCF was defined as the fold increase in serum HI 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, in subjects 18-60 years and older and 18-64 years and older, following the CHMP. | At Day 182 | 
| Number of A/California Influenza Related Cases | Influenza related cases included: A/California/7/2009 (H1N1)v-like influenza illness (ILI) cases, pneumonia cases, RT-qPCR confirmed influenza, culture confirmed influenza and RT-qPCR confirmed influenza with pneumonia. | From Day 0 up to the end of ILI surveillance (Day 385) | 
| Number of ILI Symptoms in All Reported ILI Cases | Assessed ILI symptoms were fever [defined as oral temperature equal to or above (≥) 38.5 degrees Celsius (°C)], myalgia (muscle aches all over the body), cough, sore throat, runny/stuffy nose, short of breath, headache, vomiting, diarrhea, chills, fatigue. | From Day 0 up to the end of ILI surveillance (Day 385) | 
| Number of ILI Symptoms in All Reported ILI Cases | Assessed ILI symptoms were fever [defined as oral temperature equal to or above (≥) 38.5 degrees Celsius (°C)], myalgia (muscle aches all over the body), cough, sore throat, runny/stuffy nose, short of breath, headache, vomiting, diarrhea, chills, fatigue. | From Day 14 post-vaccination through the end of ILI surveillance (Day 385) | 
| 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. Safety results were tabulated according to age stratification: adults aged 18-64 years and older (>64y). | During the 7-day (Days 0-6) post-vaccination period | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, fever [defined as axillary temperature equal to or above (≥) 38.0 degrees Celsius (°C)], headache, joint pain at other location, muscle aches, shivering and sweating. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. Safety results were tabulated according to age stratification: adults aged 18-64 years and older (>64y). | During the 7-day (Days 0-6) post-vaccination period | 
| 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], basophils [BAS], total bilirubin [T/BIL], bilirubin direct [BIL/D], creatinine [CREA], eosinophils [EOS], hematocrit [HEM], haemoglobin [Hgb], lymphocytes [LYM], monocytes [MON], neutrophils [NEU], platelets [PLA], red blood cells [RBC], blood urea nitrogen [BUN] and white blood cells [WBC]. Levels of haematological/biochemical parameters assessed with respect to normal laboratory values were - unknown, below, within and above for subjects aged 18-64 years (18-64y) and >64 years old (>64y). | At Days 7 and 21 | 
| 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. Safety results were tabulated according to age stratification: adults aged 18-64 years and older (>64y). | Throughout the entire study period (Day 0 - Day 385) | 
| Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs) | Potential immune-mediated diseases (pIMDs) represent a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. Safety results were tabulated according to age stratification: adults aged 18-64 years and older (>64y). | Throughout the entire study period (Day 0 - Day 385) | 
| 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. Safety results were tabulated according to age stratification: adults aged 18-64 years and older (>64y). | Within the 42-day (Days 0-41) post-vaccination period | 
| 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. Safety results were tabulated according to age stratification: adults aged 18-64 years and older (>64y). | Throughout the entire study period (Day 0 - Day 385) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GSK Bio's influenza vaccine GSK2340274A, Influenza Vaccines, GSK Bio's influenza vaccine GSK2340273A, influenza infection