Evaluate Safety & Immunogenicity of a Pandemic Influenza Vaccine (GSK1562902A) in Adults Over 60 Years of Age

Phase 2

Completed

• Conditions: Influenza
• Interventions: Biological: Pandemic influenza vaccine (GSK1562902A) (adjuvanted or not); Biological: Fluarix

• Registration Number: NCT00397215
• Lead Sponsor: GlaxoSmithKline

Brief Summary

The present study is designed to evaluate the immunogenicity and safety of a single or double dose of the pandemic influenza candidate vaccine (GSK1562902A), administered following a two-administration schedule (21 days apart) in adults over 60 years of age. The persistence of influenza antibodies will also be evaluated 24 months after vaccination.

Detailed Description

The present study is designed to evaluate the immunogenicity and safety of a single or double dose of the candidate vaccine in healthy elderly persons. The candidate vaccine will be administered following a two-administration schedule (21 days apart) in adults over 60 years of age. The persistence of H5N1 influenza antibodies will also be evaluated up to two years after vaccination (neutralizing antibodies will only be evaluated in a subset of subjects in the adjuvanted groups). Single and double dose of H5N1 vaccine non-adjuvanted vaccine will be used as comparator.

Study Timeline

• Study First Submitted: 2006-11-07
• Study First Submitted QC: 2006-11-07
• Study First Posted: 2006-11-08
• Study Start: 2006-11-17
• Primary Completion: 2009-09-14
• Study Completion: 2009-09-14
• Results First Submitted: 2012-12-19
• Results First Submitted QC: 2013-03-28
• Results First Posted: 2013-05-20
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-12
• Last Update Posted: 2019-06-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 437

Inclusion Criteria

• Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
• A male or female aged 61 years or above at the time of the first vaccination.
• Written informed consent obtained from the subject.
• Healthy subjects or subjects with well controlled underlying disease.

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Exclusion Criteria

• Administration of the licensed MF59-containing vaccines, e.g. Fluad™ or Addigrip™ or virosome-based influenza vaccines such as Inflexal V™, InfectoVac Flu™ or Invivac™ during the 2006-2007 influenza season.
• Administration of licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrolment in this study.
• Planned administration of a vaccine not foreseen by the study protocol up to 30 days after the second vaccination with H5N1 vaccine.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first administration of the study vaccine.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• History of chronic alcohol consumption and/or drug abuse.
• History of hypersensitivity to vaccines.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (including egg and thiomersal allergy).
• Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• Acute disease at the time of enrolment.
• Serious chronic disease including any medically significant chronic pulmonary, cardiovascular, renal, neurological, psychiatric or metabolic disorder, as determined by medical history and physical examination.
• Administration of immunoglobulins and/or any blood products within the three months preceding the first vaccination or during the study.
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days prior to the first vaccination, or planned use during the study period.
• Any condition which, in the opinion of the investigator, prevents the subject from participation in the study.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GSK1562902A 2 Group	Pandemic influenza vaccine (GSK1562902A) (adjuvanted or not)	Subjects aged 61 years or older at the time of first vaccination received 1 dose of GSK1562902A non-adjuvanted vaccine at Day 0. The vaccine was administered intramuscularly, in the deltoid region of the non-dominant arm.
GSK1562902A 2 Group	Fluarix	Subjects aged 61 years or older at the time of first vaccination received 1 dose of GSK1562902A non-adjuvanted vaccine at Day 0. The vaccine was administered intramuscularly, in the deltoid region of the non-dominant arm.
GSK1562902A 1 Group	Pandemic influenza vaccine (GSK1562902A) (adjuvanted or not)	Subjects aged 61 years or older at the time of first vaccination received 1 dose of GSK1562902A adjuvanted vaccine at Day 0. The vaccine was administered intramuscularly, in the deltoid region of the non-dominant arm.
GSK1562902A 1 Group	Fluarix	Subjects aged 61 years or older at the time of first vaccination received 1 dose of GSK1562902A adjuvanted vaccine at Day 0. The vaccine was administered intramuscularly, in the deltoid region of the non-dominant arm.
GSK1562902A 3 Group	Fluarix	Subjects aged 61 years or older at the time of first vaccination received 2 doses of GSK1562902A adjuvanted vaccine at Days 0 and 21. The vaccine was administered in the deltoid region of each arm.
GSK1562902A 4 Group	Pandemic influenza vaccine (GSK1562902A) (adjuvanted or not)	Subjects aged 61 years or older at the time of first vaccination received 2 doses of GSK1562902A non-adjuvanted vaccine at Days 0 and 21. The vaccine was administered in the deltoid region of each arm.
GSK1562902A 3 Group	Pandemic influenza vaccine (GSK1562902A) (adjuvanted or not)	Subjects aged 61 years or older at the time of first vaccination received 2 doses of GSK1562902A adjuvanted vaccine at Days 0 and 21. The vaccine was administered in the deltoid region of each arm.
GSK1562902A 4 Group	Fluarix	Subjects aged 61 years or older at the time of first vaccination received 2 doses of GSK1562902A non-adjuvanted vaccine at Days 0 and 21. The vaccine was administered in the deltoid region of each arm.

Primary Outcome Measures

Name	Time	Method
Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease.	At Day 180	The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0. The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1).
Number of Seroprotected Subjects Against 2 Strains of Influenza Disease	At Month 24	A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1).
Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease	At Month 24	The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0. The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1).
Neutralizing Antibody Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Two Strains of Influenza Disease.	At Day 180	Titers are presented as geometric mean titers (GMTs). The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1). The reference seropositivity cut-off value was ≥ 1:28. This outcome only covers results from the adjuvanted groups.
Number of Seroconverted Subjects Against 2 Strains of Influenza Disease.	At Month 24	A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer \<1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and at least a four-fold increase in post-vaccination titer. The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1).
Number of Seroconverted Subjects for Neutralizing Antibody Response Against 2 Strains of Influenza Disease.	At Month 24	A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer \<1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and at least a four-fold increase in post-vaccination titer. The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1). This outcome only covers results from the adjuvanted groups.
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Two Strains of Influenza Disease.	At Month 24	Titers are presented as geometric mean titers (GMTs). The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1). The reference seropositivity cut-off value was ≥ 1:10.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Any and Grade 3 Solicited Local Symptoms.	During the 7-day follow-up period (Days 0 to 6) after any vaccination	Assessed solicited local symptoms were ecchymosis, induration, pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 ecchymosis/induration/redness/swelling = ecchymosis/induration/redness/swelling spreading beyond 100 millimeters (mm) of injection site.
Number of Subjects With Abnormalities in Assessed Biochemical and Hematological Laboratory Parameters.	At Days 0, 2, 21 and 23.	Assessed parameters were alanine aminotransferase (ALT), basophils (BAS), creatinine (CREA), eosinophils (EOS), haematocritis (HEM), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC) and white blood cells (WBC). Per parameter and range, it was assessed whether laboratory values of the subjects were below normal, normal or above the normal range. This outcome presents NEU, PLA, RBC, URE and WBC results.
Number of Subjects With Serious Adverse Events (SAEs)	During the entire study period (Day 0 to Month 24).	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. Note: The study period was divided into 4 consecutive periods (Days 0-51, Days 52-180 \[Month 6\], Months 6-12 and Months 12-24), for which SAEs were collected.
Geometric Mean of Influenza-specific Cluster of Differentiation (CD) 4/CD8 T-cells.	At Days 0, 21 and 42	The geometric mean was calculated for cluster of differentiation (CD) 4/CD 8 T-cells (per million) producing at least one cytokine beside either of the following: CD40 ligand \[CD40L\], interleukin-2 \[IL-2\], interferon gamma \[INF-g\] and tumor necrosis factor-alpha \[TNF-α\].
Geometric Mean of Influenza-specific Cluster of Differentiation (CD) 4/CD8 T-cells	At Day 180	The geometric mean was calculated for cluster of differentiation (CD) 4/CD 8 T-cells (per million) producing at least one cytokine beside either of the following: CD40 ligand \[CD40L\], interleukin-2 \[IL-2\], tumor necrosis factor-alpha \[TNF-α\] or interferon-gamma \[IFN-γ\].
Number of Subjects With Adverse Events of Specific Interest (AESIs)	During the entire study period (Day 0 to Month 24)	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. Note: No AESIs were reported during the entire study period.
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs).	During the 21-day (Days 0-20) follow-up period after first vaccination and during the 30-day (Days 0-29) follow-up period after second 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. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms.	During the 7-day follow-up period (Days 0 to 6) after any vaccination	Assessed solicited general symptoms were arthralgia, fatigue, fever \[defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], headache, myalgia, 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.

Trial Locations

Locations (1)

GSK Investigational Site; 🇮🇹 Ragusa, Sicilia, Italy