Clinical trial NCT00430521: Safety & Immunogenicity of an Alternative Immunization Schedule of GSK Bio's Pandemic Influenza Vaccine (GSK1119711A)
Official title: Reactogenicity and Immunogenicity Study of GlaxoSmithKline Biologicals' Pandemic Influenza Vaccine (GSK1119711A) Administered According to Different Vaccination Schedules
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Influenza Vaccines
Keywords: Pandemic Flu
Pandemic influenza vaccine (GSK1119711A)
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-02-02
Enrollment: 512
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 aim of the study is to assess the safety \& immunogenicity of a pandemic influenza vaccine administered at 2 different time points. 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 should be enrolled in the study.
* 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 be abstinent or have used adequate contraceptive precautions for 30 days prior to first vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series.

Exclusion Criteria:

* Administration of licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrolment in this study.
* History of vaccination with investigational influenza pandemic vaccine.
* History of administration of an experimental/licensed vaccine
* Planned administration of a vaccine not foreseen by the study protocol during the following periods: from Day 0 up to Day 51; from 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to Month 6 and Month 12; from Month 6 up to Month 6 + 30 days; from Month 12 up to Month 12 + 30 days.
* 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, based on medical history and physical examination
* 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 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: Number of Subjects With H5N1 Haemagglutination-inhibition (HI) Antibody Concentrations Above the Cut-off Value
timeFrame: At Day 0
measure: Number of Subjects With H5N1 Haemagglutination-inhibition (HI) Antibody Concentrations Above the Cut-off Value
timeFrame: At Month 6
measure: Number of Subjects With H5N1 Haemagglutination-inhibition (HI) Antibody Concentrations Above the Cut-off Value
timeFrame: At Month 6 + 7 Days
measure: Number of Subjects With H5N1 Haemagglutination-inhibition (HI) Antibody Concentrations Above the Cut-off Value
timeFrame: At Month 6 + 21 Days
measure: Geometric Mean Titers (GMTs) of H5N1 HI Antibodies
timeFrame: At Day 0
measure: Geometric Mean Titers (GMTs) of H5N1 HI Antibodies
timeFrame: At Month 6
measure: Geometric Mean Titers (GMTs) of H5N1 HI Antibodies
timeFrame: At Month 6 + 7 Days
measure: Geometric Mean Titers (GMTs) of H5N1 HI Antibodies
timeFrame: At Month 6 + 21 Days
measure: Seroconversion Factor for H5N1 Haemagglutination-inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 6
measure: Seroconversion Factor for H5N1 Haemagglutination-inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 6 + 7 Days
measure: Seroconversion Factor for H5N1 Haemagglutination-inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 6 + 21 Days
measure: Number of Seroconverted Subjects for H5N1 Haemagglutination-inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 6
measure: Number of Seroconverted Subjects for H5N1 Haemagglutination-inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 6 + 7 Days
measure: Number of Seroconverted Subjects for H5N1 Haemagglutination-inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 6 + 21 Days
measure: Number of Seroprotected Subjects for H5N1 Haemagglutination-inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Day 0
measure: Number of Seroprotected Subjects for H5N1 Haemagglutination-inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 6
measure: Number of Seroprotected Subjects for H5N1 Haemagglutination-inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 6 + 7 Days
measure: Number of Seroprotected Subjects for H5N1 Haemagglutination-inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 6 + 21 Days
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses, up to 6/12 months + 7 days
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses, up to 12 months + 7 days
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day (Days 0-29) post-primary vaccination period (Month 6 + 30 days)
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day (Days 0-29) post-booster vaccination period (Month 12 + 30 days)
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During the entire study period (Day 0 to Month 18)
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the entire study period (Day 0 to Month 18)
measure: Number of Booster Seroconverted Subjects Against 2 Strains of Influenza Disease
timeFrame: At Month 6 + 7 Days
measure: Number of Booster Seroconverted Subjects Against 2 Strains of Influenza Disease
timeFrame: At Month 6 + 21 days
measure: Booster Factor of H5N1 HI Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 6 + 7 Days
measure: Booster Factor of H5N1 HI Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 6 + 21 Days
Secondary outcomes:
measure: GMTs of H5N1 HI Antibodies Against 2 Strains of Influenza Disease for Groups Who Received Booster Dose at Month 12
timeFrame: At Day 0, Day 21, Day 42, Month 6, Month 12, Month 12 + 7 Days, Month 12 + 21 Days and at Month 18
measure: Number of Seroconverted Subjects for H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 12
timeFrame: At Day 21, Day 42, Month 6, Month 12, Month 12 + 7 Days, Month 12 + 21 Days
measure: Number of Seroconverted Subjects for H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 12
timeFrame: At Month 12 + 7 Days, Month 12 + 21 Days and Month 18
measure: Seroconversion Factor for H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received the Booster Dose at Month 12
timeFrame: At Day 21, Day 42, Month 6, Month 12, Month 12 + 7 Days, Month 12 + 21 Days
measure: Number of Seroprotected Subjects for H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received the Booster Dose at Month 12
timeFrame: At Day 0, Day 21, Day 42, Month 6, Month 12, Month 12 + 7 Days, Month 12 + 21 Days
measure: GMTs of H5N1 HI Antibody Titers, for Groups Who Received Booster Dose at Month 6
timeFrame: At Day 0, Day 21, Day 42, Month 6, Month 6+ 7 Days, Month 6+ 21 Days, Month 12 and at Month 18
measure: Number of Seroconverted Subjects for H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 6
timeFrame: At Day 21, Day 42, Month 6, Month 6 + 7 Days, Month 6 + 21 Days, Month 12 and Month 18
measure: Seroconversion Factor for H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received the Booster Dose at Month 6
timeFrame: At Day 21, Day 42, Month 6, Month 6 + 7 Days, Month 6 + 21 Days, Month 12 and Month 18
measure: Number of Seroprotected Subjects for H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 6
timeFrame: At Day 0, Day 21, Day 42, Month 6, Month 6+ 7 Days, Month 6+ 21 Days, Month 12 and Month 18
measure: Number of Booster Seroconverted Subjects Against 2 Strains of Influenza Disease, A/Vietnam/1194/2004 and A/Indonesia/5/2005, for Groups Who Received Booster Dose at Month 12
timeFrame: At Month 12 + 7 Days, Month 12 + 21 Days and Month 18
measure: Booster Factor of H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 12
timeFrame: At Month 12 + 7 Days and at Month 12 + 21 Days
measure: Booster Factor of H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 12
timeFrame: At Month 12 + 7 Days, Month 12 + 21 Days and at Month 18
measure: Frequency of Influenza-specific CD4/CD8 T-cells (Per 10E6 T-cells) in Tests Identified as Producing at Least Two Out of Four Different Cytokines, for Groups Who Received Booster Dose at Month 6
timeFrame: At Day 0, Month 6, Month 6 + 7 Days, Month 6 + 21 Days, Month 12 and Month 18
measure: Frequency of Influenza-specific CD4/CD8 T-cells (Per 10E6 T-cells) in Tests Identified as Producing at Least Two Out of Four Different Cytokines, for Groups Who Received Booster Dose at Month 12
timeFrame: At Day 0, Month 6, Month 12, Month 12 + 7 Days, Month 12 + 21 Days and Month 18
measure: GMTs of H5N1 Neutralizing Antibodies Against 2 Strains of Influenza Disease, for Adults Who Received Booster Dose at Month 6
timeFrame: At Day 0, Day 21, Day 42, Month 6, Month 6 + 7 Days, Month 6 + 21 Days and Month 12
measure: GMTs of H5N1 Neutralizing Antibodies Against 2 Strains of Influenza Disease, for Adults Who Received Booster Dose at Month 12
timeFrame: At Day 0, Day 21, Day 42, Month 6, Month 12, Month 12 + 7 Days and Month 12 + 21 Days
measure: GMTs of H5N1 Neutralizing Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 6
timeFrame: At Day 0, Day 21, Day 42, Month 6, Month 6 + 7 Days, Month 6 + 21 Days, Month 12 and Month 18
measure: GMTs of H5N1 Neutralizing Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 12
timeFrame: At Day 0, Day 21, Day 42, Month 6, Month 12, Month 12 + 7 Days, Month 12 + 21 Days and Month 18
measure: Number of Seroconverted Subjects for H5N1 Neutralizing Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 6
timeFrame: At Day 21, Day 42, Month 6, Month 6 + 7 Days, Month 6 + 21 Days and Month 12
measure: Number of Seroconverted Subjects for H5N1 Neutralizing Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 12
timeFrame: At Day 21, Day 42, Month 6, Month 12, Month 12 + 7 Days and Month 12 + 21 Days
measure: Number of Booster Seroconverted Subjects Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 6
timeFrame: At Month 6 + 7 Days, Month 6 + 21 Days, Month 12 and Month 18
measure: Number of Booster Seroconverted Subjects Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 12
timeFrame: At Month 12 + 7 Days and Month 12 + 21 Days
measure: Number of Booster Seroconverted Subjects Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 12
timeFrame: At Month 12 + 7 Days, Month 12 + 21 Days and Month 18
Other outcomes:
Locations:
city: Deggendorf
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Neu-Ulm
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Regensburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Wuerzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Schwerin
country: Germany
facility: GSK Investigational Site
state: Mecklenburg-Vorpommern
city: Witten
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Gillard P, Caplanusi A, Knuf M, Roman F, Walravens K, Moris P, Drame M, Schwarz TF. An assessment of prime-boost vaccination schedules with AS03A -adjuvanted prepandemic H5N1 vaccines: a randomized study in European adults. Influenza Other Respir Viruses. 2013 Jan;7(1):55-65. doi: 10.1111/j.1750-2659.2012.00349.x. Epub 2012 Mar 9.
citation: Schwarz TF, Horacek T, Knuf M, Damman HG, Roman F, Drame M, Gillard P, Jilg W. Single dose vaccination with AS03-adjuvanted H5N1 vaccines in a randomized trial induces strong and broad immune responsiveness to booster vaccination in adults. Vaccine. 2009 Oct 23;27(45):6284-90. doi: 10.1016/j.vaccine.2009.01.040.