Clinical trial NCT00502593: Evaluate Safety & Immunogenicity of a Pandemic Influenza Vaccine (GSK1562902A) in Children
Official title: A Phase II, Randomized, Open, Controlled Study to Evaluate the Safety and Immunogenicity of Different Formulations of a Pandemic Influenza Vaccine Candidate (Split Virus Formulation Adjuvanted With AS03) Given Following a Two-administration Schedule (21 Days Apart) in Children Between 3 and 9 Years of Age.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Keywords: Influenza
Pandemic Influenza Vaccine (GSK1562902A)
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-07-17
Enrollment: 138
Sex: ALL
Minimum age (years): 3
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The present study is designed to evaluate in children (aged between 3 and 9 years) the immunogenicity and safety of different antigen doses of the candidate vaccine (GSK1562902A) administered following a two-administration schedule (21 days apart). Subjects in the control group will receive Fluarix. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed description: This 107066 study is a participating study to the broader NCT00502593 study, which included 2 other studies, the 108498 and 108500 studies. The NCT00502593 study had a staggered design (subjects from each group being enrolled sequentially into 2 age strata, '6-9 years' 1st, and '3-5 years' next) and was run in 3 phases, phases A (Study 107066), B (Study 108498) and C (Study 108500). In each phase, the decision to vaccinate subjects aged 3-5 years and to administer a 2nd injection to subjects aged 6-9 years was made based on safety data collected on Days 0-6 after the 1st injection for the subjects aged 6-9 years. Decision to start Phase B was made on complete safety data including those collected on Day 28 of Phase A (7 days after the 2nd injection) for each age group. A similar approach was to be used to start Phase C. As safety data in Phase A did not raise any safety concerns, Phases B and C were run in parallel.

Eligibility criteria: Inclusion Criteria:

* Children who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.
* Children aged between and including 3 and 9 years of age at the time of first vaccination.
* Written informed consent obtained from the parent(s) or guardian of the subject.
* Healthy children as established by medical history and clinical examination before entering the study.
* Subjects who are likely to reside in the vicinity of the study center for the duration of the study.

Exclusion criteria:

* Use of any investigational or non-registered product (drug or vaccine) other than the investigational vaccine within 30 days prior to the enrolment in this study, or planned use during the study period.
* 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 the exception of routine childhood inoculations which cannot be delayed, but which must not be administered on the same day as the investigational vaccine candidate.
* Administration of the interpandemic influenza vaccine 21 days prior to Day 0 or up to Day 51.
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the enrolment in this study.
* Any chronic drug therapy to be continued during the study period, with the exception of inhalative treatment for seasonal allergies or asthma.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by 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 vaccines used in this study.
* History of any neurological disorders or seizures.
* Acute disease at the time of enrolment.
* Administration of immunoglobulins and/or any blood products within the three months prior to the enrolment in this study or planned during the study.
* Any condition which, in the opinion of the investigator, renders the subject unfit for participation in the study

Primary outcomes:
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Day 0
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Day 21
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Day 42
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 6
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 12
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 24
measure: Number of Seroconverted Subjects Against 2 Strains of Influenza Disease
timeFrame: At Day 21
measure: Number of Seroconverted Subjects Against 2 Strains of Influenza Disease
timeFrame: At Day 42
measure: Number of Seroconverted Subjects Against 2 Strains of Influenza Disease
timeFrame: At Month 6
measure: Number of Seroconverted Subjects Against 2 Strains of Influenza Disease
timeFrame: At Month 12
measure: Number of Seroconverted Subjects Against 2 Strains of Influenza Disease
timeFrame: At Month 24
measure: Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Day 21
measure: Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Day 42
measure: Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Month 6
measure: 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
timeFrame: At Month 24
measure: Number of Seroprotected Subjects Against the 2 Strains of Influenza Disease
timeFrame: At Day 0
measure: Number of Seroprotected Subjects Against the 2 Strains of Influenza Disease
timeFrame: At Day 21
measure: Number of Seroprotected Subjects Against the 2 Strains of Influenza Disease
timeFrame: At Day 42
measure: Number of Seroprotected Subjects Against the 2 Strains of Influenza Disease
timeFrame: At Month 6
measure: Number of Seroprotected Subjects Against the 2 Strains of Influenza Disease
timeFrame: At Month 12
measure: Number of Seroprotected Subjects Against the 2 Strains of Influenza Disease
timeFrame: At Month 24
measure: Number of Subjects With Any, Grade 3 and Related Solicited Local Symptoms
timeFrame: During the 7 day follow-up period after each vaccination
measure: Number of Subjects With Any, Grade 3 and Related Solicited Local Symptoms
timeFrame: During the 7-day follow-up period after each vaccination
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) follow-up period after any vaccination
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) follow-up period after any vaccination
measure: Number of Subjects With Any, Grade 3 and Related Solicited Local Symptoms
timeFrame: During the 7-day follow-up period after each vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the entire study (Day 0 to Month 24)
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events
timeFrame: During a 21 day follow-up period after the first vaccination, during a 30-day follow-up period after the second vaccination
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Alanine Aminotransferase (ALT) for Subjects in Study Phase A
timeFrame: At Days 21 and 42 and Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Aspartate Aminotransferase (AST) in Study Phase A
timeFrame: At Days 21 and 42 and Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Blood Urea Nitrogen (BUN) in Study Phase A
timeFrame: At Days 21 and 42 and Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Creatine Phosphokinase (CPK) in Study Phase A
timeFrame: At Days 21 and 42 and Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Blood Creatinine (CREA) in Study Phase A
timeFrame: At Days 21 and 42 and Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Lactate Dehydrogenase (LDH) in Study Phase A
timeFrame: At Days 21 and 42 and Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Alanine Aminotransferase (ALT) for Subjects in Study Phase B
timeFrame: At Days 21 and 42 and Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Aspartate Aminotransferase (AST) in Study Phase B
timeFrame: At Days 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Blood Urea Nitrogen (BUN) in Study Phase B
timeFrame: At Days 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Creatine Phosphokinase (CPK) in Study Phase B
timeFrame: At Days 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Blood Creatinine (CREA) in Study Phase B
timeFrame: At Days 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Lactate Dehydrogenase (LDH) in Study Phase B
timeFrame: At Days 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Alanine Aminotransferase (ALT) for Subjects in Study Phase C
timeFrame: At Days 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Aspartate Aminotransferase (AST) in Study Phase C
timeFrame: At Days 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Blood Urea Nitrogen (BUN) in Study Phase C
timeFrame: At Days 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Changed Status as Regards to the Biochemical Parameter Blood Creatinine (CREA) in Study Phase C
timeFrame: At Days 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Changed Status With Regards to Creatine Phosphokinase (CPK) in Study Phase C
timeFrame: At Days 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Changed Status With Regards to Lactate Dehydrogenase (LDH) in Study Phase C
timeFrame: At Days 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Respect to Alanine Aminotransferase (ALT) in Study Phase A
timeFrame: At Days 0, 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Respect to Aspartate Aminotransferase (AST) in Study Phase A
timeFrame: At Days 0, 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Regards to Blood Urea Nitrogen (BUN) in Study Phase A
timeFrame: At Days 0, 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Regards to Creatinine (CREA) in Study Phase A
timeFrame: At Days 0, 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Regards to Creatine Phosphokinase (CPK) in Study Phase A
timeFrame: At Days 0, 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Regards to Lactate Dehydrogenase (LDH) in Study Phase A
timeFrame: At Days 0, 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Respect to Alanine Aminotransferase (ALT) in Study Phase B
timeFrame: At Days 0, 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Regards to Aspartate Aminotransferase (AST) in Study Phase B
timeFrame: At Days 0, 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Regards to Creatinine (CREA) in Study Phase B
timeFrame: At Days 0, 21 and 42 and at Month 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Regards to Lactate Dehydrogenase (LDH) in Study Phase B
timeFrame: At Days 0, 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Regards to Blood Urea Nitrogen (BUN) in Study Phase B
timeFrame: At Days 0, 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Regards to Blood Urea Nitrogen (BUN) in Study Phase C
timeFrame: At Days 0, 21 and 42 and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Respect to Alanine Aminotransferase (ALT) in Study Phase C
timeFrame: At Days 0, 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Regards to Creatine Phosphokinase (CPK) in Study Phase B
timeFrame: At Days 0, 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Respect to Aspartate Aminotransferase (AST) in Study Phase C
timeFrame: At Days 0, 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Regards to Creatine Phosphokinase (CPK) in Study Phase C
timeFrame: At Days 0, 21, and 42, and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Regards to Creatinine (CREA) in Study Phase C
timeFrame: At Days 0, 21 and 42 and at Months 6, 12 and 24
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Regards to Lactate Dehydrogenase (LDH) in Study Phase C
timeFrame: At Days 0, 21 and 42 and at Months 6, 12 and 24
Secondary outcomes:
measure: Titers for Serum Neutralizing Antibodies Against 1 Strain of Influenza Disease
timeFrame: At Days 0, 21 and 42
measure: Titers for Serum Neutralizing Antibodies Against 1 Strain of Influenza Disease
timeFrame: At Days 0, 21 and 42
measure: Titers for Serum Neutralizing Antibodies Against 1 Strain of Influenza Disease
timeFrame: At Days 0, 21 and 42
measure: Number of Seroconverted Subjects Against One Strain of Influenza Disease With Respect to Serum Neutralizing Antibodies
timeFrame: At Days 21 and 42
measure: Number of Seroconverted Subjects Against One Strain of Influenza Disease With Respect to Serum Neutralizing Antibodies
timeFrame: At Days 21 and 42
measure: Number of Seroconverted Subjects Against One Strain of Influenza Disease With Respect to Serum Neutralizing Antibodies
timeFrame: At Days 21 and 42
measure: Titers for Serum Neutralizing Antibodies Against 2 Strains of Influenza Disease
timeFrame: At Months 6, 12 and 24
measure: Number of Seroconverted Subjects Against 2 Strains of Influenza Disease as Regards to Neutralizing Antibody Response
timeFrame: At Months 6, 12 and 24.
measure: Number of Subjects With Adverse Events of Specific Interest (AESIs)
timeFrame: Throughout the entire study period, from Day 0 to Month 24
Other outcomes:
Locations:
city: Blanes (Girona)
country: Spain
facility: GSK Investigational Site
city: L'Eliana, Valencia
country: Spain
facility: GSK Investigational Site
city: Paiporta, Valencia
country: Spain
facility: GSK Investigational Site
city: Quart De Poblet, Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Diez-Domingo J, Baldo JM, Planelles-Catarino MV, Garces-Sanchez M, Ubeda I, Jubert-Rosich A, Mares J, Garcia-Corbeira P, Moris P, Teko M, Vanden Abeele C, Gillard P. Phase II, randomized, open, controlled study of AS03-adjuvanted H5N1 pre-pandemic influenza vaccine in children aged 3 to 9 years: follow-up of safety and immunogenicity persistence at 24 months post-vaccination. Influenza Other Respir Viruses. 2015 Mar;9(2):68-77. doi: 10.1111/irv.12295. Epub 2015 Feb 5.
citation: Diez-Domingo J, Garces-Sanchez M, Baldo JM, Planelles MV, Ubeda I, JuBert A, Mares J, Moris P, Garcia-Corbeira P, Drame M, Gillard P. Immunogenicity and Safety of H5N1 A/Vietnam/1194/2004 (Clade 1) AS03-adjuvanted prepandemic candidate influenza vaccines in children aged 3 to 9 years: a phase ii, randomized, open, controlled study. Pediatr Infect Dis J. 2010 Jun;29(6):e35-46. doi: 10.1097/INF.0b013e3181daf921.