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

Study Overview
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Brief Summary
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The objective of this study is to evaluate the immunogenicity and safety of GSK Biologicals' investigational vaccine GSK2340272A in adults aged 18 to 60 years.

Detailed Description
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This Protocol Posting has been updated following Protocol amendment 1, October 2009. The impacted section is the outcomes measures section.

Official Title
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Safety and Immunogenicity Study of GSK Biologicals' Influenza Vaccine GSK2340272A in Adults Aged 18 to 60 Years

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK2340272A
* Biological: GSK2340269A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female aged 18 to 60 years 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 health event satisfying the definition of an SAE, 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 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 two 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 >= 37.5°C, or acute symptoms greater than mild severity on the scheduled date of first vaccination. Diagnosed with cancer, or treatment for cancer, within the past three years. Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection. Clinically or virologically confirmed influenza infection within six months preceding the study start. Chronic administration of immunosuppressants or other immune modifying drugs within six months of study enrolment or planned administration during the study period. For corticosteroids, this will mean a dose equivalent to 20 mg/day of prednisone or equivalent for persons for > two weeks. Inhaled and topical steroids 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 and without a clinically-apparent bleeding tendency, are eligible. An acute evolving neurological disorder or history of Guillain-Barré syndrome. Administration of any vaccines within 30 days before vaccination. 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. 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
Maximum Age: 60 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: GSK2340272A Group<br>Healthy male or female adults, between and including 18 to 60 years of age, who received two doses of GSK2340272A vaccine, administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and of the dominant arm at Day 21. | Biological: GSK2340272A<br>* Two intramuscular injections in the deltoid region of the non-dominant arm.<br>|
| Experimental: GSK2340269A Group<br>Healthy male or female adults, between and including 18 to 60 years of age, who received two doses of GSK2340269A vaccine, administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and of the dominant arm at Day 21. | Biological: GSK2340269A<br>* Two intramuscular injections in the deltoid region of the non-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 Against Flu A/California/7/2009 (H1N1) 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/California/7/2009 (H1N1)v-like influenza (Flu A/CAL/7/09). | 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. | At Day 21 | 
| Geometric Mean Fold Change (GMFR) for HI Antibodies Against Flu A/California/7/2009 (H1N1) 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. | At Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Were Seropositive for Hemagglutination Inhibition (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. | At Days 0, 21 and 42 | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/California/7/2009 (H1N1) 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. | At Days 0, 21 and 42 | 
| Number of Subjects Who Were Seropositive for HI Antibodies Against Flu A/California/7/2009 (H1N1) Virus Strain | A seropositive subject was defined as a vaccinated subject with a serum HI titer ≥ 1:10, that usually is accepted as indicating protection. | At Days 0, 21 and 42 | 
| Titers for Serum HI Antibodies Against Flu A/California/7/2009 (H1N1) 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. | 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. | At Days 182 and 364 | 
| Titers for Serum HI Antibodies Against the Flu A/California/7/2009 (H1N1) 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 greater than or equal to (≥) 1:10. | At Days 182 and 364 | 
| Number of Subjects Who Were Seropositive for HI Antibodies Against Flu A/California/7/2009 (H1N1) Virus Strain | A seropositive subject was defined as a vaccinated subject with a serum HI titer ≥ 1:10, that usually is accepted as indicating protection. | At Days 182 and 364 | 
| Titers for Serum HI Antibodies Against Flu A/California/7/2009 (H1N1) 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. | At Days 182 and 364 | 
| Number of Seroconverted (SCR) Subjects for HI Antibodies Against Flu A/California/7/2009 (H1N1) Strain of Influenza Disease | 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). | At Days 21 and 42 | 
| Number of Seroconverted (SCR) Subjects for HI Antibodies Against the Flu A/California/7/2009 (H1N1) Strain of Influenza Disease | 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). | At Days 182 and 364 | 
| Number of Seroconverted (SCR) Subjects for HI Antibodies Against Flu A/California/7/2009 (H1N1) Strain of Influenza Disease | Seroconversion was defined as: For initially seronegative subjects (antibody titer < 10 post-vaccination), antibody titer ≥ 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). | 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. | 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 ≥ 1:40, that usually is accepted as indicating protection. | At Days 182 and 364 | 
| Geometric Mean Fold Change (GMFR) for HI Antibodies Against Flu A/California/7/2009 (H1N1) 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. | At Days 21 and 42 | 
| Geometric Mean Fold Change (GMFR) for HI Antibodies Against Flu A/California/7/2009 (H1N1) 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. | At Days 182 and 364 | 
| 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 post-vaccination period following Dose 1 (Day 0-6), Dose 2 (Day 21-27), and across doses (Day 0-6 and 21-27) | 
| Number of Days With Solicited Local Symptoms | The number of days with any solicited local symptoms reported during the solicited post-vaccination period. No subjects in GSK2340269A Group reported redness or swelling. | During the 7-day post-vaccination period following Dose 1 (Day 0-6), Dose 2 (Day 21-27), and across doses (Day 0-6 and 21-27) | 
| 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 or their 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 post-vaccination period following Dose 1 (Day 0-6), Dose 2 (Day 21-27), and across doses (Day 0-6 and 21-27) | 
| Number of Days With Solicited General Symptoms | The number of days with any solicited general symptoms reported during the solicited post-vaccination period. No subjects from the GSK2340269A Group reported any temperature after Dose 2. | During the 7-day post-vaccination period following Dose 1 (Day 0-6), Dose 2 (Day 21-27), and across doses (Day 0-6 and 21-27) | 
| 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. | From Day 0 up to Day 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. | Within 21 days after the first vaccination and 63 days after the second vaccination (Day 0 - Day 20 and Day 21 - Day 84) | 
| 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 364) | 

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