Safety, Immunogenicity Study of GSK Biologicals' Pandemic Influenza Candidate Vaccine (H1N1) (GSK2340272A)

Study Overview
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Brief Summary
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This trial is designed to assess the safety and immunogenicity of a prime-boost schedule of GSK Biologicals' investigational vaccine GSK2340272A in children aged between 6 and 35 months. This protocol posting has been updated following protocol amendment 4, March 2010. The protocol posting sections impacted are number of subjects, primary and secondary endpoints and intervention.

Official Title
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Safety and Immunogenicity Study of GSK Biologicals' Pandemic Influenza Candidate Vaccine (GSK2340272A) in Children Aged 6 to 35 Months

Conditions
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Influenza

Intervention / Treatment
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* Biological: Pandemic influenza vaccine GSK2340272A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol Children, male or female, aged between 6 and 35 months at the time of first study vaccination. Written informed consent obtained from the parent(s) or LAR(s) of the subject. Healthy children, as established by medical history and clinical examination when entering the study. Parent/LAR with access to a consistent means of telephone contact, land line or mobile, but NOT a pay phone or other multiple-user device. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of the study vaccine or planned use during the study period. Clinically or virologically confirmed influenza infection within six months preceding the study start. Planned administration of any vaccine 30 days prior and 30 days after any study vaccine administration. Chronic administration of immunosuppressants or other immune-modifying drugs within three months prior to enrolment in this study or planned administration during the study period. 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 History of any neurological disorders or seizures. Acute disease and/or fever 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. Child in Care.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 35 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK 2340272A F1 Group<br>Healthy male or female children, between and including 6 and 35 months of age, who received 2 doses of GSK2340272A Formulation 1 (F1) vaccine according to a 0, 21-day schedule, intramuscularly administered in the deltoid region of the arm or in the anterolateral region of the thigh if the subject was less than (<) 12 months at study entry. | Biological: Pandemic influenza vaccine GSK2340272A<br>* Two primary intramuscular (IM) injections<br>|
| Experimental: GSK 2340272A F2 Group<br>Healthy male or female children, between and including 6 and 35 months of age, who received 2 doses of GSK2340272A Formulation 2 (F2) vaccine according to a 0, 21-day schedule, intramuscularly administered in the deltoid region of the arm or in the anterolateral region of the thigh if the subject was less than (<) 12 months at study entry. | Biological: Pandemic influenza vaccine GSK2340272A<br>* Two primary intramuscular (IM) injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects for H1N1 Haemagglutination Inhibition (HI) Antibodies | Seropositivity was defined as H1N1 HI antibody titers greater than or equal to (≥) 1:10. The strain assessed was Flu A/California/7/2009 (H1N1). | At Day 0 | 
| Number of Seropositive Subjects for H1N1 Haemagglutination Inhibition (HI) Antibodies | Seropositivity was defined as H1N1 HI antibody titers greater than or equal to (≥) 1:10. The strain assessed was Flu A/California/7/2009 (H1N1). | At Day 42 | 
| Titers for H1N1 Haemagglutination Inhibition (HI) Antibodies | Antibody titers are presented as geometric mean titers (GMTs), with a reference seropositivity cut-off value greater than or equal to (≥) 1:10. The strain assessed was Flu A/California/7/2009 (H1N1). | At Day 0 | 
| Titers for H1N1 Haemagglutination Inhibition (HI) Antibodies | Antibody titers are presented as geometric mean titers (GMTs), with a reference seropositivity cut-off value greater than or equal to (≥) 1:10. The strain assessed was Flu A/California/7/2009 (H1N1). | At Day 42 | 
| Number of Seroconverted Subjects in Terms of H1N1 Haemagglutination Inhibition (HI) Antibodies | Seroconversion (SCR) was defined as the percentage of vaccinees that have 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 4-fold increase in post-vaccination titer. The strain assessed was Flu A/California/7/2009 (H1N1). | At Day 42 | 
| Number of Seroprotected Subjects for H1N1 Haemagglutination Inhibition (HI) Antibodies | Seroprotection (SPR) was defined as the percentage of vaccinees with a serum HI titer ≥ 1:40 that usually is accepted as indicating protection. The strain assessed was Flu A/California/7/2009 (H1N1). | At Day 42 | 
| Seroconversion Factor (SCF) for H1N1 Haemagglutination Inhibition (HI) Antibody Titers | Seroconversion factor was defined as the fold increase in serum HI geometric mean titers (GMTs) post-vaccination compared to pre-vaccination. The strain assessed was Flu A/California/7/2009 (H1N1). | At Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects for H1N1 Haemagglutination Inhibition (HI) Antibodies | Seropositivity was defined as H1N1 HI antibody titers greater than or equal to (≥) 1:10. The strain assessed was Flu A/California/7/2009 (H1N1). | At Days 0, 21, 42, and at Month 11-12 | 
| Titers for H1N1 Haemagglutination Inhibition (HI) Antibodies | Antibody titers are presented as geometric mean titers (GMTs), with a reference seropositivity cut-off value greater than or equal to (≥) 1:10. The strain assessed was Flu A/California/7/2009 (H1N1). | At Days 0, 21, 42 and at Month 11-12 | 
| Number of Seroconverted Subjects in Terms of H1N1 Haemagglutination Inhibition (HI) Antibody Titers | Seroconversion (SCR) was defined as the percentage of vaccinees that have 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 4-fold increase in post-vaccination titer. The strain assessed was Flu A/California/7/2009 (H1N1). | At Days 21, 42 and at Month 11-12 | 
| Number of Seroprotected Subjects for H1N1 Haemagglutination Inhibition (HI) Antibodies | Seroprotection (SPR) was defined as the percentage of vaccinees with a serum HI titer ≥ 1:40 that usually is accepted as indicating protection. The strain assessed was Flu A/California/7/2009 (H1N1). | At Days 0, 21, 42 and at Month 11-12 | 
| Seroconversion Factor (SCF) for H1N1 Haemagglutination Inhibition (HI) Antibody Titers | Seroconversion factor was defined as the fold increase in serum HI geometric mean titers (GMTs) post-vaccination compared to pre-vaccination. The strain assessed was Flu A/California/7/2009 (H1N1). | At Days 21, 42 and at Month 11-12 | 
| Titers for Serum Neutralising Antibodies | Antibody titers are presented as geometric mean titers (GMTs), with a reference seropositivity cut-off value greater than or equal to (≥) 1:8. The strain assessed was Flu A/Neth/602/09. | At Days 0, 21 and 42 | 
| Titers for Serum Neutralising Antibodies | Antibody titers are presented as geometric mean titers (GMTs), with a reference seropositivity cut-off value greater than or equal to (≥) 1:8. The strain assessed was Flu A/Neth/602/09. | At Days 0, 21, 42 and at Month 11-12 | 
| Number of Subjects With Vaccine Response for Serum Neutralising Antibodies | Vaccine response rate was defined as the percentage of vaccinees with a minimum 4-fold increase in titer at post-vaccination for neutralising antibody response. For initially seronegative subjects, antibody titer ≥ 1:32 after vaccination; For initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. The strain assessed was Flu A/Neth/602/2009. | At Days 21 and 42 | 
| Number of Subjects With Vaccine Response for Serum Neutralising Antibodies | Vaccine response rate was defined as the percentage of vaccinees with a minimum 4-fold increase in titer at post-vaccination for neutralising antibody response. For initially seronegative subjects, antibody titer ≥ 1:32 after vaccination; For initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. The strain assessed was Flu A/Neth/602/2009. | At Days 21, 42 and at Month 11-12 | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. | During the 7-day (Days 0-6) post-vaccination period after each dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 loss of appetite= not eating at all. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 7-day (Days 0-6) post-vaccination period after each dose and across doses | 
| Number of Subjects With Any Medically-attended Events (MAEs) | MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any MAE(s) = Occurrence of any MAE(s) regardless of intensity grade or relation to vaccination. | During the entire study period (Day 0 up to Month 7 and Day 0 up to Month 11-12) | 
| Number of Subjects With Any Adverse Events of Specific Interest (AESIs)/ Potential Immune-mediated Disease (pIMDs) | 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. Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. | During the entire study period (Day 0 up to Month 11-12) | 
| Number of Subjects With Normal/Abnormal Biochemical Levels | Among biochemical parameters assessed were: alanine aminotrasferase [ALAT], aspartate aminotransferase [ASAT], bilirubin total [BIL/T], bilirubin direct [BIL/D], creatinine [CREA] and blood urea nitrogen [BUN]. Levels of biochemical parameters assessed with respect to normal laboratory values were - unknown, below, within and above. | At Days 0, 21 and 42 | 
| 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 a 21 day follow-up period after the first vaccination and during a 62-day follow-up period after the second vaccination (Days 0 - 84) | 
| 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. | During the entire study period (Day 0 up to Month 11-12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza infection, GSK Bio's influenza vaccine GSK2340272A