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

Influenza Clinical Trial

Official title:

Evaluate Immunogenicity & Safety of a Single or Double-dose of the Pandemic Influenza Candidate Vaccine (GSK1562902A) Given Following a Two-administration Schedule (21 Days Apart) in Adults Over 60 Yrs

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00397215
• Other study ID #: 108251
• Secondary ID: 1082521112751112
• Status: Completed
• Phase: Phase 2
• Start date: November 17, 2006
• Est. completion date: September 14, 2009

Study information

• Verified date: February 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 437
• Est. completion date: September 14, 2009
• Est. primary completion date: September 14, 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

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.

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• Pandemic influenza vaccine (GSK1562902A) (adjuvanted or not)
intramuscular injection
• Fluarix
Intramuscular injection. All subjects not vaccinated with an influenza vaccine for the 2006-2007 season received Fluarix NH 2006/2007 (i.e. interpandemic GSK's influenza vaccine) at least 3 weeks before administration of the first dose of H5N1 vaccine.

Locations

Country	Name	City	State
Belgium	GSK Investigational Site	Dour
Belgium	GSK Investigational Site	Gozée
Belgium	GSK Investigational Site	Libramont
Belgium	GSK Investigational Site	Mont-Godinne
Belgium	GSK Investigational Site	Sprimont
Belgium	GSK Investigational Site	Tessenderlo
Belgium	GSK Investigational Site	Watermael-Boitsfort
Italy	GSK Investigational Site	Genova	Liguria
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Monserrato Cagliari	Sardegna
Italy	GSK Investigational Site	Ragusa	Sicilia
Italy	GSK Investigational Site	Sassari	Sardegna

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Belgium,  Italy, 

References & Publications (2)

Gillard P, Giet D, Heijmans S, Dramé M, Walravens K, Roman F. Long-term outcome of the humoral and cellular immune response of an H5N1 adjuvanted influenza vaccine in elderly persons: 2-year follow-up of a randomised open-label study. Trials. 2014 Oct 29;15:419. doi: 10.1186/1745-6215-15-419. — View Citation

Heijmans S, De Meulemeester M, Reynders P, Giet D, Demanet E, Devresse PY, Icardi G, Dramé M, Roman F, Gillard P. Immunogenicity profile of a 3.75-µg hemagglutinin pandemic rH5N1 split virion AS03A-adjuvanted vaccine in elderly persons: a randomized trial. J Infect Dis. 2011 Apr 15;203(8):1054-62. doi: 10.1093/infdis/jiq174. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Two Strains of Influenza Disease.	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.	At Days 0, 21 and 42
Primary	Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease.	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).	At Days 21 and 42
Primary	Number of Seroprotected Subjects Against 2 Strains of Influenza Disease	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).	At Days 0, 21 and 42
Primary	Neutralizing Antibody Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Two Strains of Influenza Disease.	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.	At Days 0 and 42
Primary	Number of Seroconverted Subjects Against 2 Strains of Influenza Disease.	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).	At Days 21 and 42
Primary	Number of Seroconverted Subjects for Neutralizing Antibody Response Against 2 Strains of Influenza Disease.	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.	At Day 42
Primary	Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Two Strains of Influenza Disease.	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.	At Day 180
Primary	Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Two Strains of Influenza Disease.	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.	At Month 12
Primary	Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Two Strains of Influenza Disease.	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.	At Month 24
Primary	Number of Seroconverted Subjects Against 2 Strains of Influenza Disease.	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).	At Day 180
Primary	Number of Seroconverted Subjects Against 2 Strains of Influenza Disease.	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).	At Month 12
Primary	Number of Seroconverted Subjects Against 2 Strains of Influenza Disease.	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).	At Month 24
Primary	Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease.	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).	At Day 180
Primary	Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease	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).	At Month 12
Primary	Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease	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).	At Month 24
Primary	Number of Seroprotected Subjects Against 2 Strains of Influenza Disease	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).	At Day 180
Primary	Number of Seroprotected Subjects Against 2 Strains of Influenza Disease	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).	At Month 12
Primary	Number of Seroprotected Subjects Against 2 Strains of Influenza Disease	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).	At Month 24
Primary	Number of Seroconverted Subjects for Neutralizing Antibody Response Against 2 Strains of Influenza Disease.	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.	At Day 180
Primary	Number of Seroconverted Subjects for Neutralizing Antibody Response Against 2 Strains of Influenza Disease.	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.	At Month 12
Primary	Number of Seroconverted Subjects for Neutralizing Antibody Response Against 2 Strains of Influenza Disease.	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.	At Month 24
Primary	Neutralizing Antibody Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Two Strains of Influenza Disease.	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.	At Month 12
Primary	Neutralizing Antibody Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Two Strains of Influenza Disease.	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.	At Month 24
Primary	Neutralizing Antibody Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Two Strains of Influenza Disease.	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.	At Day 180
Secondary	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. Note: No AESIs were reported during the entire study period.	During the entire study period (Day 0 to Month 24)
Secondary	Number of Subjects With Any and Grade 3 Solicited Local Symptoms.	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.	During the 7-day follow-up period (Days 0 to 6) after any vaccination
Secondary	Number of Subjects With Abnormalities in Assessed Biochemical and Hematological Laboratory Parameters.	Assessed parameters were alanine aminotransferase (ALT), aspartate aminotransferase (AST), basophils (BAS), creatinine phosphokinase (CRPH), creatinine (CREA), eosinophils (EOS), haemoglobin (HEM), lactate dehydrogenase (LDE), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), urea (URE) 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 results for ALT, AST, BAS, CREA and CRPH.	At Days 0, 2, 21 and 23
Secondary	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. 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.	During the entire study period (Day 0 to Month 24).
Secondary	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.	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
Secondary	Number of Subjects With Abnormalities in Assessed Biochemical and Hematological Laboratory Parameters.	Assessed parameters were alanine aminotransferase (ALT), aspartate aminotransferase (AST), basophils (BAS), creatinine phosphokinase (CRPH), creatinine (CREA), eosinophils (EOS), haemoglobin (HEM), lactate dehydrogenase (LDE), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), urea (URE) 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 EOS, HEM, LDE, LYM and MON results.	At Days 0, 2, 21 and 23.
Secondary	Geometric Mean of Influenza-specific Cluster of Differentiation (CD) 4/CD8 T-cells.	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-a] or interferon-gamma [IFN-?].	At Month 12
Secondary	Geometric Mean of Influenza-specific Cluster of Differentiation (CD) 4/CD8 T-cells.	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-a] or interferon-gamma [IFN-?].	At Month 24
Secondary	Number of Subjects With Abnormalities in Assessed Biochemical and Hematological Laboratory Parameters.	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.	At Days 0, 2, 21 and 23.
Secondary	Geometric Mean of Influenza-specific Cluster of Differentiation (CD) 4/CD8 T-cells.	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-a].	At Days 0, 21 and 42
Secondary	Geometric Mean of Influenza-specific Cluster of Differentiation (CD) 4/CD8 T-cells	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-a] or interferon-gamma [IFN-?].	At Day 180
Secondary	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms.	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.	During the 7-day follow-up period (Days 0 to 6) after any vaccination

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