Study of GSK Biologicals' Influenza Vaccine Arepanrix™ in Japanese Adults 65 Years of Age or Older

Study Overview
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Brief Summary
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The purpose of this study is to comply with the post marketing condition to the exceptional approval of Arepanrix™ in Japan and to assess the immunogenicity and safety of GSK Biologicals' H1N1 influenza vaccine healthy Japanese adults 65 years of age or older.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Influenza Vaccine Arepanrix™ (GSK2340274A) in Adults 65 Years of Age or Older

Conditions
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Influenza

Intervention / Treatment
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* Biological: Arepanrix™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese male and female adults 65 years of age or older at time of vaccination. Subjects who the investigator believes can and will comply with the requirements of the protocol. Written informed consent obtained from the subject. Good general health as assessed by medical history and physical examination. 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. Non-childbearing potential is defined as current tubal ligation, hysterectomy, ovariectomy or post-menopause. 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 and for 2 months after study vaccination. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the dose of study vaccine, or planned use during the study period. History of previous administration of a pandemic H1N1 vaccine. Presence of significant acute or chronic, uncontrolled medical or psychiatric illness. Presence or 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 >= 37.5 °C, or acute symptoms greater than mild severity on the scheduled date of vaccination. 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 accepted and may enrol, 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 prophylactic tamoxifen are excepted and may enroll. Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune modifying drugs within 6 months of study enrolment or planned administration during the study period. For corticosteroids, this will mean a dose equivalent to 10 mg/day of prednisone or equivalent when administered for > 2 weeks. Topical, intra-articularly injected, or inhaled glucocorticoids, topical calcineurin inhibitors or imiquimod are allowed. Receipt of any immunoglobulins and/or any blood products within three 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 within 6 months of receipt of seasonal influenza vaccination. Administration of any vaccines within 30 days before vaccination or planned administration before blood sampling at Day 21 and within 30 days prior to blood sampling at Day 182. Any known or suspected allergy to any constituent of influenza vaccines or component used in the manufacturing process of the study vaccine; a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine. Excessive underweight [Body Mass Index (BMI) < 18.5] or excessive obesity (BMI >= 30). Any conditions which, in the opinion of the investigator, prevents the subjects from participating in the study. Clinically or virologically confirmed influenza infection within 12 months preceding the study start.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arepanrix Group<br>Healthy Japanese male and female adults, 65 years of age or older, who received one dose of the study vaccine Arepanrix™, administered intramuscularly in the deltoid region of the non-dominant arm at Day 0. | Biological: Arepanrix™<br>* Intramuscular administration, one dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects for Hemagglutination Inhibition (HI) Antibodies | Seroconversion (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/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09). | At Day 21 | 
| Number of Seroprotected Subjects for HI Antibodies | Seroprotection (SPR) was defined as the proportion of subjects with H1N1 reciprocal HI titers equal to or above (≥) 40 against the tested vaccine virus. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09). | At Day 21 | 
| Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/California/7/2009 Strain of Influenza Disease | 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/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09). | At Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With HI Antibody Concentrations Above the Cut-off Value | 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/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09). | At Days 0 and 21 | 
| Number of Subjects With HI Antibody Concentrations Above the Cut-off Value | 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/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09). | At Days 0 and 182 | 
| Titers for Serum HI Antibodies Against Flu A/California/7/2009 Strain | 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/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09). | At Days 0 and 21 | 
| Titers for Serum HI Antibodies Against Flu A/California/7/2009 Strain | 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/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09). | At Days 0 and 182 | 
| Number of Seroconverted Subjects for HI Antibodies | 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/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09). | At Day 182 | 
| Number of Seroprotected Subjects for HI Antibodies | Seroprotection (SPR) was defined as the proportion of subjects with H1N1 reciprocal HI titers equal to or above (≥) 40 against the tested vaccine virus. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09). | At Days 0 and 182 | 
| GMFR for HI Antibodies Against Flu A/California/7/2009 Strain of Influenza Disease | 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/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09). | At Day 182 | 
| Number of Subjects With Neutralizing Antibody Concentrations Above the Cut-off Value | Seropositivity cut-off values assessed were equal to or above (≥) 1:8 in the sera of subjects seronegative before vaccination. The flu strain assessed was Flu A/Netherlands/602/2009 (H1N1) (Flu A/Neth/602/09). | At Days 0 and 21 | 
| Number of Subjects With Neutralizing Antibody Concentrations Above the Cut-off Value | Seropositivity cut-off values assessed were equal to or above (≥) 1:8 in the sera of subjects seronegative before vaccination. The flu strain assessed was Flu A/Netherlands/602/2009 (H1N1) (Flu A/Neth/602/09). | At Days 0 and 182 | 
| Titers for Neutralizing Antibodies Against Flu A/Netherlands/602/09 Strain of Influenza Disease | Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:8. The flu strain assessed was Flu A/Netherlands/602/2009 (H1N1) (Flu A/Neth/602/09). | At Days 0 and 21 | 
| Titers for Neutralizing Antibodies Against Flu A/Netherlands/602/09 Strain of Influenza Disease | Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:8. The flu strain assessed was Flu A/Netherlands/602/2009 (H1N1) (Flu A/Neth/602/09). | At Days 0 and 182 | 
| Number of Subjects With Vaccine Response Rate (VRR) for Neutralizing Antibodies Against Flu A/Netherlands/602/09 Strain of Influenza Disease | VRR for microneutralization titers was defined as the proportion of vaccinees with at least a 4-fold increase in post-vaccination reciprocal titer relative to Day 0. The flu strain assessed was Flu A/Netherlands/602/2009 (H1N1) (Flu A/Neth/602/09). | At Day 21 | 
| Number of Subjects With VRR for Neutralizing Antibodies Against Flu A/Netherlands/602/2009 Strain of Influenza Disease | VRR for microneutralization titers was defined as the proportion of vaccinees with at least a 4-fold increase in post-vaccination reciprocal titer relative to Day 0. The flu strain assessed was Flu A/Netherlands/602/2009 (H1N1) (Flu A/Neth/602/09). | 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 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. | During the 7-day (Days 0-6) post-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. | 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, 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 = fever ≥ 39.0°C to ≤ 40.0°C. Related = symptom assessed by the investigator as causally related to the study vaccination. | During the 7-day (Days 0-6) post-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. | During the 7-day (Days 0-6) post-vaccination period | 
| Number of Subjects With Medically Attended AEs (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. | During the 21-day (Days 0-20) post-vaccination period | 
| Number of Subjects With 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. | During the 42-day (Days 0-41) post-vaccination period | 
| Number of Subjects With Potential Immune-mediated Diseases (pIMDs) | pIMDs are 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. | During the entire study period (from Day 0 up to Day 182) | 
| Number of Subjects With Normal or Abnormal Hematological and Biochemical Levels | Among hematological and biochemical parameters assessed were alanine aminotransferase (ALAT), albumin, alkaline phosphatase (AP), aspartate aminotransferase (ASAT), basophils, total bilirubin, bilirubin conjugated/direct, cholesterol, chloride, creatine, creatine kinase (CK), eosinophils, gamma-glutamyl transpeptidase (GGT), hematocrit, hemoglobin, potassium, lactate dyhydrogenase (LDH), lymphocytes, monocytes, sodium, neutrophils, platelets, protein, red blood cells, urate/uric acid, blood urea nitrogen (BUN) and white blood cells. Unknown = value unknown for the specified time point and laboratory parameter; Below = value below the laboratory reference range defined for the specified time point and laboratory parameter; Within = value within the laboratory reference range defined for the specified time point and laboratory parameter; Above = value above the laboratory reference range defined for the specified time point and laboratory parameter. | At Day 0 and Day 7 | 
| Number of Subjects With Abnormal Urine Sampling Parameters | Among assessed urine sampling parameters were glucose, protein, red blood cells and urobilinogen. | At Day 0 and Day 7 | 
| Number of Subjects With 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. | During the 21-day (Days 0-20) post-vaccination period | 
| Number of Subjects With Unsolicited 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. | During the 42-day (Days 0-41) post-vaccination period | 
| 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 Day 182) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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elderly, post-marketing, H1N1, Clinical trial, pandemic influenza