Clinical trial NCT00449670: Assess Consistency of Immunogenicity of GlaxoSmithKline Biologicals' Pandemic Influenza Vaccine (GSK1562902A) in Adults
Official title: Assess the Consistency of the Immunogenicity of a GlaxoSmithKline Biologicals' Pandemic Influenza Vaccine (GSK1562902A) in Adults Aged Between 18 and 60 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Influenza Vaccines
Keywords: Influenza
Influenza Vaccine
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-03-20
Enrollment: 1206
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The present study is designed to assess the lot-to-lot consistency of the immunogenicity of a GlaxoSmithKline Biologicals' pandemic influenza candidate vaccine (GSK1562902A) in adults aged between 18 and 60 years.

Detailed description: The protocol posting has been updated to reflect changes due to an amendment to the protocol (addition of an exclusion criterion). The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes that they can and will comply with the requirements of the protocol
* A male or female between, and including, 18 and 60 years of age at the time of the first vaccination.
* Written informed consent obtained from the subject.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* If the subject is female, she must be of non-childbearing potential; or, if of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series.

Exclusion Criteria:

* Administration of any 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 during the following periods: from Day 0 up to Day 51, 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to Month 6; from Month 6 up to Month 6 + 30 days (or Month 6 + 51 days for the control groups).
* Previous vaccination with a pandemic candidate vaccine or a vaccine containing the same adjuvant as the study vaccine.
* Previous proven contact with H5N1 wild type virus (i.e. contact with an individual with laboratory-confirmed H5N1 infection, or contact with an animal (e.g. poultry) which died as a result of H5N1 infection).
* 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 candidate vaccines.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, or autoimmune diseases such as Guillain Barre Syndrome, based on medical history and physical examination (no laboratory testing required).
* History of hypersensitivity to vaccines.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
* History of chronic alcohol consumption and/or drug abuse.
* Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
* Serious chronic disease including any medically significant chronic pulmonary, cardiovascular, renal, neurological, psychiatric or metabolic disorder, as determined by medical history and physical examination.
* Acute disease at the time of enrolment.
* Administration of immunoglobulins and/or any blood products within the 3 months preceding the first administration of the candidate vaccine or during the study.
* Lactating women.
* 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.

Primary outcomes:
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: Before vaccination (Day 0)
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: Within 21 days following 2-dose primary vaccination (at Day 42)
Secondary outcomes:
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: Within 21 days following the first primary vaccination dose (Day 21)
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D) and at Month 6+42 days (M6+42D)
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D) and at Month 6+42 days (M6+42D) and at Month 12 (M12)
measure: Titers for Serum Neutralizing (SN) Antibodies Against 2 Strains of Influenza Disease
timeFrame: Before vaccination at Day 0 (D0) and within 21 days following 2-dose primary vaccination at Day 42 (D42)
measure: Titers for Serum Neutralization (SN) Antibodies Against 2 Strains of Influenza Disease
timeFrame: Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D) and at Month 6+42 days (M6+42D)
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease in Adults Who Had Not Received the Booster Dose at Month 6
timeFrame: At Day 0, at Day 21, at Day 42, at Month 6 and at Month 12
measure: Titers for Serum Neutralization (SN) Antibodies Against 2 Strains of Influenza Disease in Adults Who Had Not Received the Booster Dose at Month 6
timeFrame: At Month 12
measure: Number of Seroconverted Subjects for HI Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Day 21 (D21) and at Day 42 (D42)
measure: Number of Seroconverted Subjects for HI Antibodies Against 2 Strains of Influenza Disease
timeFrame: Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D) and at Month 6+42 days (M6+42D)
measure: Number of Seroconverted Subjects for HI Antibodies Against 2 Strains of Influenza Disease for Adults Who Received the Booster Dose at Month 6 - Booster Phase
timeFrame: Following booster vaccination at Month 6 +21 days (M6+21D) and Month 6 +42 days (M6+42D)
measure: Number of Seroconverted Subjects for HI Antibodies Against 2 Strains of Influenza Disease for Adults Who Received the Booster Dose at Month 6 - Booster Phase
timeFrame: At Month 12
measure: Number of Seroconverted Subjects for Neutralizing Antibodies Against 2 Strains of Influenza Disease
timeFrame: Within 21 days following 2-dose primary vaccination at Day 42
measure: Number of Seroconverted Subjects for Neutralizing Antibodies Against 2 Strains of Influenza Disease - Booster Phase
timeFrame: Following booster vaccination at Month 6+21 days (M6+21D) and at Month 6+42 days (M6+42D)
measure: Number of Seroconverted Subjects for HI Antibodies Against 2 Strains of Influenza Disease for Adults Who Have Not Received Booster at Month 6
timeFrame: At Day 21, Day 42, Month 6 and Month 12 following primary vaccination
measure: Number of Seroconverted Subjects for Neutralizing Antibodies Against 2 Strains of Influenza Disease for Subjects Not Boosted at Month 6
timeFrame: At Month 12
measure: Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At day 21 and Day 42
measure: Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: Before booster vaccination at Month 6 (M6) and within 21 days following each booster dose: At Month 6 + 21 days (M6+21D) and, for H5N1 Un-adjuvanted Group only, at Month 6 + 42 days (M6+42D)
measure: Booster Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: Within 21 days following each booster dose: At Month 6 + 21 days (M6+21D) and, for H5N1 Un-adjuvanted Group only, at Month 6 + 42 days (M6+42D)
measure: Booster Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 12
measure: Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease for Subjects Not Boosted at Month 6
timeFrame: At Day 21, at Day 42, at Month 6 and at Month 12
measure: Number of Subjects Seroprotected Against 2 Strains of Influenza Disease
timeFrame: Before primary vaccination at Day 0 and within 21 days following each primary vaccination dose at Day 21 and at Day 42.
measure: Number of Subjects Seroprotected Against 2 Strains of Influenza Disease
timeFrame: Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D) and at Month 6+42 days (M6+42D)
measure: Number of Seroprotected Subjects Against 2 Strains of Influenza Disease
timeFrame: Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D), at Month 6+42 days (M6+42D) and at Month 12 (M12)
measure: Number of Subjects Seroprotected Against 2 Strains of Influenza Disease for Subjects Not Boosted at Month 6
timeFrame: At Day 0, Day 21, Day 42, Month 6 and Month 12
measure: Frequency of Influenza-specific Cluster of Differentiation 4+ (CD4+) T Cells Expressing at Least 2 Markers Among the Analyzed Cytokines Upon in Vitro Stimulation
timeFrame: Within 21 days of each primary vaccine dose: at Day 21 and at Day 42
measure: Frequency of Influenza-specific Cluster of Differentiation 8+ (CD8+) T Cells Expressing at Least 2 Markers Among the Analyzed Cytokines Upon in Vitro Stimulation
timeFrame: Within 21 days of each primary vaccine dose: at Day 21 and at Day 42
measure: Frequency of Influenza-specific Cluster of Differentiation 4+ (CD4+) T Cells Expressing at Least 2 Markers Among the Analyzed Cytokines Upon in Vitro Stimulation
timeFrame: Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D), at Month 6+42 days (M6+42D) and at Month 12 (M12)
measure: Frequency of Influenza-specific Cluster of Differentiation 8+ (CD8+) T Cells Expressing at Least 2 Markers Among the Analyzed Cytokines Upon in Vitro Stimulation
timeFrame: Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D), at Month 6+42 days (M6+42D) and at Month 12 (M12)
measure: Frequency of Influenza-specific Cluster of Differentiation 4+ (CD4+) T Cells Expressing at Least 2 Markers Among the Analyzed Cytokines Upon in Vitro Stimulation for Subjects Not Boosted at Month 6
timeFrame: At Month 6 and Month 12
measure: Frequency of Influenza-specific Cluster of Differentiation 8+ (CD8+) T Cells Expressing at Least 2 Markers Among the Analyzed Cytokines Upon in Vitro Stimulation for Subjects Not Boosted at Month 6
timeFrame: At Month 6 and at Month 12
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-days (Days 0-6) post-primary vaccination period following each dose and overall
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-days (Days 0-6) post-primary vaccination period following each dose and overall
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms - Booster Phase
timeFrame: During the 7-days (Days 0-6) post-booster vaccination period
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms - Booster Phase
timeFrame: During the 7-days (Days 0-6) post-booster vaccination period
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: During the primary phase (from Day 0 to Month 6)
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: During the booster phase (from Month 6 to Month 12)
measure: Number of Subjects With Serious Adverse Events (SAEs).
timeFrame: During the primary phase (from Day 0 to Month 6)
measure: Number of Subjects With Serious Adverse Events (SAEs).
timeFrame: During the booster phase (from Month 6 to Month 12)
measure: Number of Subjects With Serious Adverse Events (SAEs) for Subjects Not Boosted at Month 6
timeFrame: From Month 6 to Month 12
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: GSK Investigational Site
city: Singapore
country: Singapore
facility: GSK Investigational Site
city: Singapore
country: Singapore
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Chu DW, Hwang SJ, Lim FS, Oh HM, Thongcharoen P, Yang PC, Bock HL, Drame M, Gillard P, Hutagalung Y, Tang H, Teoh YL, Ballou RW; H5N1 Flu Study Group for Hong Kong, Singapore, Taiwan and Thailand. Immunogenicity and tolerability of an AS03(A)-adjuvanted prepandemic influenza vaccine: a phase III study in a large population of Asian adults. Vaccine. 2009 Dec 9;27(52):7428-35. doi: 10.1016/j.vaccine.2009.07.102. Epub 2009 Aug 13.
citation: Chu DW, Kwong AS, Tsui WW, Wang JH, Ngai CK, Wan PK, Ong G, Tang HW, Roman F, Dram M, Bock HL. Cross-clade immunogenicity and safety of an AS03A-adjuvanted prepandemic H5N1 influenza vaccine in Hong Kong. Hong Kong Med J. 2011 Feb;17(1):39-46.
citation: Hwang SJ, Chang SC, Yu CJ, Chan YJ, Chen TJ, Hsieh SL, Lai HY, Lin MH, Liu JY, Ong G, Roman F, Drame M, Bock HL, Yang PC. Immunogenicity and safety of an AS03(A)-adjuvanted H5N1 influenza vaccine in a Taiwanese population. J Formos Med Assoc. 2011 Dec;110(12):780-6. doi: 10.1016/j.jfma.2011.11.009. Epub 2011 Dec 23.
citation: Thongcharoen P, Auewarakul P, Hutagalung Y, Ong G, Gillard P, Drame M, Bock HL. Cross-clade immunogenicity and antigen-sparing with an AS03(A)-adjuvanted prepandemic influenza vaccine in a Thai population. J Med Assoc Thai. 2011 Aug;94(8):916-26.
citation: Gillard P, Chu DW, Hwang SJ, Yang PC, Thongcharoen P, Lim FS, Drame M, Walravens K, Roman F. Long-term booster schedules with AS03A-adjuvanted heterologous H5N1 vaccines induces rapid and broad immune responses in Asian adults. BMC Infect Dis. 2014 Mar 15;14:142. doi: 10.1186/1471-2334-14-142.