Clinical trial NCT00652743: Immunogenicity of GSK Biologicals' Pandemic Influenza Vaccine (GSK1562902A) at Different Boosting Vaccination Schedules
Official title: Immunogenicity of GSK Biologicals' Pandemic Influenza Vaccine (GSK1562902A) at Different Boosting Vaccination Schedules
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Keywords: immunogenicity
safety
GSK pandemic candidate vaccine
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-04-04
Enrollment: 845
Sex: ALL
Minimum age (years): 19
Maximum age (years): 61
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Today, the leading contender for the next influenza pandemic is H5N1, a strain of avian virus found primarily in domestic and wild birds. Experts warn that the next influenza pandemic is imminent and could be severe. Prevention and control will depend on the rapid production and worldwide distribution of specific pandemic vaccines. Candidate 'pandemic-like' vaccines must be developed and tested in clinical trials to determine the best formulation and vaccination schedule.

The purpose of this study is to assess the immune response of a candidate pandemic vaccine. The protocol posting deals with objectives \& outcome measures of the secondary phase of this study. The objectives and outcome measures of the primary phase are presented in a separate protocol posting (NCT number = 00449670).


Eligibility criteria: Inclusion Criteria:

* Subjects who completed participation in primary phase of this study.
* Subjects who the investigator believes can and will comply with the requirements of the protocol should be enrolled in the study.
* 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 be post-menopausal; 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 4 weeks prior to enrolment in this study.
* Planned administration of a vaccine not foreseen by the study protocol: 4 weeks prior to any visit or within 30 days after vaccination.
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first visit or planned use during the study
* 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 three months preceding the first visit or planned use during the study.
* Pregnant or 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 visit, 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: Number of Subjects Boosted at Month 12 With Haemagglutinin-inhibition (HI) Antibody Concentrations Above the Cut-off Value
timeFrame: At Month 12 + 21 days
measure: Titers for Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 12
timeFrame: At Month 12 + 21 days
measure: Number of Subjects Boosted at Month 36 With HI Antibody Concentrations Above the Cut-off Value
timeFrame: At Month 36 + 21 days
measure: Titers for Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 36
timeFrame: At Month 36 + 21 days
measure: Booster Vaccine Response for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 12
timeFrame: At Month 12 + 21 days
measure: Booster Vaccine Response for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 36
timeFrame: At Month 36 + 21 Days
measure: Geometric Mean Fold Rise (GMFR) for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 12
timeFrame: At Month 12 + 21 days
measure: Geometric Mean Fold Rise (GMFR) for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 36
timeFrame: At Month 36 +21 days
measure: Number of Subjects Boosted at Month 12 Seroprotected (SPR) for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease
timeFrame: At Month 12 + 21 days
measure: Number of Subjects Boosted at Month 36 Seroprotected (SPR) for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease
timeFrame: At Month 36 + 21 days
Secondary outcomes:
measure: Number of Seropositive Subjects for H5N1 HI Antibodies
timeFrame: At Months 18, 24, 30 and 36
measure: Number of Seropositive Subjects for H5N1 HI Antibodies
timeFrame: At Months 42 and 48
measure: Booster Vaccine Response for H5N1 HI Antibodies for Subjects Boosted at Month 6 and Month 12
timeFrame: At Months 18, 24 and 30
measure: Number of Subjects Boosted at Month 36 Seroconverted for H5N1 HI Antibodies
timeFrame: At Months 18, 24 and 30
measure: Booster Vaccine Response for H5N1 HI Antibodies
timeFrame: At Months 36, 42 and 48
measure: Geometric Mean Fold Rise (GMFR) for H5N1 HI Antibodies
timeFrame: At Months 18, 24, 30
measure: Geometric Mean Fold Rise (GMFR) for H5N1 HI Antibodies
timeFrame: At Months 36, 42 and 48
measure: Number of Seroprotected (SPR) Subjects for H5N1 HI Antibodies
timeFrame: At Months 18, 24 and 30
measure: Number of Seroprotected (SPR) Subjects for H5N1 HI Antibodies
timeFrame: At Months 36, 42 and 48
measure: Titers for Serum Neutralizing Antibodies
timeFrame: At Months 6/12, 6/12 + 21 days, 24, 36 and 48
measure: Booster Vaccine Response for Neutralizing Antibodies
timeFrame: At Months 6/12/36 + 21 days, 12, 24, 36 and 48
measure: Number of Subjects With Neutralizing Antibody Concentrations Above the Cut-off Value
timeFrame: At Months 6/12/36 + 21 days, 12, 24, 36 and 48
measure: Number of Subjects With Neutralizing Antibody Concentrations Above the Cut-off
timeFrame: At Months 6/12/36 + 21 days, 12, 24, 36 and 48
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period - subjects boosted at Month 12 and Month 36
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptom
timeFrame: During the 7-day (Days 0-6) post-vaccination period - subjects boosted at Month 12 and 36
measure: Number of Subjects With Adverse Events of Specific Interest (AESIs)
timeFrame: During the entire study period (From Month 12 to Month 48)
measure: Frequency of Antigen-specific CD4 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines (for A/Indonesia/05/2005 Strain)
timeFrame: At Months 6, 12, 18, 24, 30, 36, 42 and 48 and at Months 6/12/36 + 21 days
measure: Frequency of Antigen-specific CD4 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines (for A/Vietnam/1194/2004 Strain)
timeFrame: At Months 6, 12, 18, 24, 30, 36, 42 and 48 and at Months 6/12/36 + 21 days
measure: Frequency of Antigen-specific CD8 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines (for A/Indonesia/05/2005 Strain)
timeFrame: At Months 6, 12, 18, 24, 30, 36, 42 and 48 and at Months 6/12/36 + 21 days
measure: Frequency of Antigen-specific CD8 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines (for A/Vietnam/1194/2004 Strain)
timeFrame: At Months 6, 12, 18, 24, 30, 36, 42 and 48 and at Months 6/12/36 + 21 days
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day (Days 0-29) follow-up period after vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the entire study period (From Month 12 up to Month 48)
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: 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.