Safety Study of Pandemic Candidate Influenza Vaccines in the Elderly Population

Phase 2

Completed

• Conditions: Influenza Vaccines; Influenza
• Interventions: Biological: SB218352_4; Biological: SB218352_2; Biological: SB218352_8AL; Biological: SB218352_2AL; Biological: SB218352_4AL; Biological: SB218352_15; Biological: SB218352_8

• Registration Number: NCT00306995
• Lead Sponsor: GlaxoSmithKline

Brief Summary

Influenza pandemics are caused by viruses that possess an Hemagglutinin molecule to which most of the population lacks immunity. If such virus is pathogenic to human and demonstrates the ability to transmit from person to person, the result is a global outbreak of disease that affects a high percentage of individuals in a short period of time and is likely to cause substantially increased mortality and morbidity in all countries of the world. Recently, purely avian influenza viruses, including the H5N1, H9N2 and H7N7 subtypes, have been directly transmitted to humans, raising concern over the possibility of a new influenza pandemic among the world's immunologically naive populations. In order to face this kind of situation, a pandemic influenza vaccine has to be developed.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2005-05-11
• Study First Submitted: 2006-02-16
• Study First Submitted QC: 2006-03-24
• Study First Posted: 2006-03-27
• Primary Completion: 2006-07-04
• Study Completion: 2006-07-04
• Results First Submitted: 2017-09-22
• Status Verified: 2020-02
• Results First Submitted QC: 2020-02-06
• Last Update Submitted: 2020-02-06
• Results First Posted: 2020-02-10
• Last Update Posted: 2020-02-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 385

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SB218352_4 Group	SB218352_4	Male and female subjects over 60 years of age, healthy or with underlying disease, received 2 doses of SB218352 pandemic influenza A formulation 3 non-adjuvanted vaccine, administered in the deltoid region of the non-dominant arm, at Day 0 and Day 21.
SB218352_2 Group	SB218352_2	Male and female subjects over 60 years of age, healthy or with underlying disease, received 2 doses of SB218352 pandemic influenza A formulation 4 non-adjuvanted vaccine, administered in the deltoid region of the non-dominant arm, at Day 0 and Day 21.
SB218352_8AL Group	SB218352_8AL	Male and female subjects over 60 years of age, healthy or with underlying disease, received 2 doses of SB218352 pandemic influenza A formulation 2 aluminium-adjuvanted vaccine, administered in the deltoid region of the non-dominant arm, at Day 0 and Day 21.
SB218352_2AL Group	SB218352_2AL	Male and female subjects over 60 years of age, healthy or with underlying disease, received 2 doses of SB218352 pandemic influenza A formulation 4 aluminium-adjuvanted vaccine, administered in the deltoid region of the non-dominant arm, at Day 0 and Day 21.
SB218352_4AL Group	SB218352_4AL	Male and female subjects over 60 years of age, healthy or with underlying disease, received 2 doses of SB218352 pandemic influenza A formulation 3 aluminium-adjuvanted vaccine, administered in the deltoid region of the non-dominant arm, at Day 0 and Day 21.
SB218352_15 Group	SB218352_15	Male and female subjects over 60 years of age, healthy or with underlying disease, received 2 doses of SB218352 pandemic influenza A formulation 1 non-adjuvanted vaccine, administered in the deltoid region of the non-dominant arm, at Day 0 and Day 21.
SB218352_8 Group	SB218352_8	Male and female subjects over 60 years of age, healthy or with underlying disease, received 2 doses of SB218352 pandemic influenza A formulation 2 non-adjuvanted vaccine, administered in the deltoid region of the non-dominant arm, at Day 0 and Day 21.

Primary Outcome Measures

Name	Time	Method
Serum Haemagglutination-inhibition (HI) Antibody Titers Against the Influenza A Virus Strain Subtype H9N2 (Anti-H9N2)	At Day 10 post Dose 1	Anti-H9N2 antibody titers were expressed as Geometric Mean Titers (GMTs).
Serum HI Antibody Titers Against the Influenza A Virus Strain Subtype H9N2 (Anti-H9N2)	At Day 21 post Dose 3 (Day 210 for Subset 1 groups and Day 386 for Subset 2 groups)	Anti-H9N2 antibody titers were expressed as Geometric Mean Titers (GMTs).
Number of Seroconverted Subjects Against Influenza A Subtype H9N2	At Day 21 post Dose 3 (Day 210 for Subset 1 groups and Day 386 for Subset 2 groups)	Seroconversion rate was defined as the percentage of vaccinees who had a pre-vaccination HI titer \< 1:10 and a post-vaccination titre ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and a minimum four-fold increase in post-vaccination titer
Seroconversion Factor for Influenza A Subtype H9N2	At Day 21 post Dose 3 (Day 210 for Subset 1 groups and Day 386 for Subset 2 groups)	Seroconversion factor was defined as the fold increase in serum HI GMTs on day 21 post Dose 3 (Day 210 for Subset 1 and Day 386 for Subset 2) compared to day 0.
Number of Seroprotected Subjects Against H9N2	At Day 21 post Dose 3 (Day 210 for Subset 1 groups and Day 386 for Subset 2 groups)	Seroprotection rate was defined as the percentage of vaccinees with a serum HI titer ≥ 1:40 after vaccination (for each vaccine strain) that usually was accepted as indicating protection.
Number of Subjects With Seroprotection Power Against H9N2	At Day 21 post Dose 3 (Day 210 for Subset 1 groups and Day 386 for Subset 2 groups)	Seroprotection power was defined as the proportion of subjects who were unprotected prior to the vaccination (HI titer \< 1:40 on day 0) and had a protective post-vaccination titer of ≥ 1:40.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Unsolicited Adverse Events (AEs)	During the 30-days (Day 0-30) post vaccination	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.
Number of Subjects With Serious Adverse Events (SAEs)	From Day 0 to Day 51	A SAE was any untoward medical occurrence which resulted in death, was life-threatening, resulted in hospitalization or prolongation of hospitalization, resulted in permanent of serious physical disability or incapacity, caused a congenital anomaly or birth defect in the offspring of a subject or might have put the subject at risk based on medical or scientific judgment or necessitated intervention to prevent such an event (e.q. invasive or malignant cancers, intensive treatment in an emergency room or at home for bronchospasm, blood dyscrasias, or convulsion that do not resulted in hospitalization).
Frequency of Antigen-specific Cluster of Differentiation 4 (CD4) T-cells	At Days 0, 10, 21 and 42 post vaccination	Among expressed immune markers were interferon-gamma (IFN-γ) and cluster of differentiation 40 - ligand (CD40-L).
Frequency of Antigen-specific CD4 T-cells	At Days 0, 10, 21 and 42 post-vaccination	Among expressed immune markers were interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-α).
Cytokine-positive CD4 T-cells Frequency	At Days 10, 21 and 42 post-vaccination	Among expressed immune markers were interleukin-2 (IL-2), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and cluster of differentiation 40 - ligand (CD40-L). Descriptive comparison of the CMI response after Dose 1 and Dose 2 of the monovalent candidate pandemic influenza A vaccine. CMI response was determined in terms of the proportion of lymphocytes (CD4+ and CD8+ per million T cells) activated in vitro by the vaccine antigen on Days 10 and 21 after the Dose 1 and on Day 21 after Dose 2 as compared to Day 0 (pre-vaccination). The results were calculated based on the individual difference between each post-vaccination timepoint (Day 10, Day 21, Day 42) and Day 0.
Frequency of Antigen-specific Cluster of Differentiation 8 (CD8) T-cells	At Days 0, 10, 21 and 42 post-vaccination	Among expressed immune markers were interferon-gamma (IFN-γ) and cluster of differentiation 40 - ligand (CD40-L).
Frequency of Antigen-specific CD8 T-cells	At Days 0, 10, 21 and 42 post-vaccination	Among expressed immune markers were interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-α).
Cytokine-positive CD8 T-cells Frequency	At Days 10, 21 and 42 post-vaccination	Among expressed immune markers were interleukin-2 (IL-2), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and cluster of differentiation 40 - ligand (CD40-L). Descriptive comparison of the CMI response after Dose 1 and Dose 2 of the monovalent candidate pandemic influenza A vaccine. CMI response was determined in terms of the proportion of lymphocytes (CD4+ and CD8+ per million T cells) activated in vitro by the vaccine antigen on Days 10 and 21 after the Dose 1 and on Day 21 after Dose 2 as compared to Day 0 (pre-vaccination). The results were calculated based on the individual difference between each post-vaccination timepoint (Day 10, Day 21, Day 42) and Day 0.
Number of Subjects With Solicited Local Symptoms	During the 4 Days post Dose 3 (Days 189-192 for Subset 1 groups and Days 365-368 for Subset 2 groups)	Assessed solicited local symptoms were pain, redness, swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = pain which prevents normal everyday activities. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm).
Number of Subjects With Solicited General Symptoms	During the 4 Days post Dose 3 (Days 189-192 for Subset 1 groups and Days 365-368 for Subset 2 groups)	Assessed solicited general symptoms were arthralgia, fatigue, fever \[defined as axilar temperature higher than (≥) 37.5 degrees Celsius (°C)\], headache, myalgia, shivering and sweating. Any = occurrence of any solicited general symptom regardless of intensity grade or relationship to the study vaccination. Grade 3 symptom = symptoms that prevented normal activity. Grade 3 fever = fever higher than (\>) 39°C. Related symptom = symptom assessed by the investigator as being casually related to the study vaccination.
Number of Subjects With Unsolicited AEs	During the 30-days post Dose 3 (Days 189-219 for Subset 1 groups and Days 365-395 for Subset 2 groups)	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.
Number of Subjects With SAEs	Within the 365-day post-vaccination period (Days 0-364 for Subset 1 groups) and within the 395-day post-vaccination period (Days 0-394 for Subset 2 groups)	A SAE was any untoward medical occurrence which resulted in death, was life-threatening, resulted in hospitalization or prolongation of hospitalization, resulted in permanent of serious physical disability or incapacity, caused a congenital anomaly or birth defect in the offspring of a subject or might have put the subject at risk based on medical or scientific judgment or necessitated intervention to prevent such an event (e.q. invasive or malignant cancers, intensive treatment in an emergency room or at home for bronchospasm, blood dyscrasias, or convulsion that do not resulted in hospitalization).
Number of Subjects With Any SAEs	Up to 30-day post Dose 3 (Days 365-394)	A SAE was any untoward medical occurrence which resulted in death, was life-threatening, resulted in hospitalization or prolongation of hospitalization, resulted in permanent of serious physical disability or incapacity, caused a congenital anomaly or birth defect in the offspring of a subject or might have put the subject at risk based on medical or scientific judgment or necessitated intervention to prevent such an event (e.q. invasive or malignant cancers, intensive treatment in an emergency room or at home for bronchospasm, blood dyscrasias, or convulsion that do not resulted in hospitalization). Only Subset 2 groups had available data for the specified time frame.
Number of Subjects With Antibody Persistence	At Days 189 and 365	Antibody persistence was evaluated in terms of seroprotection rate (SPR) against influenza A subtype H9N2 and seroconversion rate (SCR) against influenza A subtype H9N2.
Seroconversion Factor (SCF) for Influenza A Subtype H9N2.	At Days 189 and 365	SCF was defined as the fold increase in serum HI GMTs at the post-vaccination time points compared to Day 0, for each vaccine strain.

Trial Locations

Locations (1)

GSK Investigational Site; 🇩🇪 Elmshorn, Schleswig-Holstein, Germany