Immunogenicity and Safety Study of a GlaxoSmithKline Biologicals' Candidate Influenza Vaccine in Healthy Children

• ClinicalTrials.gov Identifier: NCT00985790
• Recruitment Status: Completed
• First Posted: September 28, 2009
• Results First Posted: March 12, 2013
• Last Update Posted: September 21, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

The purpose of the present study is to assess the immunogenicity and safety of vaccine GSK2321138A in children.

Condition or disease	Intervention/treatment	Phase
Influenza	Biological: Influenza vaccine GSK2321138A; Biological: Fluarix™	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 599 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety Study of a GlaxoSmithKline Biologicals' Candidate Influenza Vaccine GSK2321138A in Healthy Children
• Study Start Date: October 8, 2009
• Actual Primary Completion Date: May 21, 2010
• Actual Study Completion Date: May 21, 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: GSK2321138A Group; Subjects aged between 18 and 47 months received the GSK2321138A. "Primed" subjects (subjects who had received a 2-dose priming immunization with Fluarix™ vaccine in study NCT00764790 - or the GSK2321138A-Primed Group) received 1 dose of GSK2321138A vaccine at Day 0. "Unprimed" subject (subjects who had not received any 2-dose priming influenza immunization in any previous year - or the the GSK2321138A-Unprimed Group) received 2 doses of GSK2321138A vaccine at Days 0 and 28. The GSK2321138A vaccine was administered intramuscularly in the deltoid of the right arm.	Biological: Influenza vaccine GSK2321138A; Intramuscular injection
Active Comparator: Fluarix Group; Subjects aged between 18 and 47 months received the Fluarix™ vaccine. "Primed" subjects (subjects who had received a 2-dose priming immunization with Fluarix™ vaccine in study NCT00764790 - or the Fluarix-Primed Group) received 1 dose of Fluarix™ vaccine at Day 0. "Unprimed" subject (subjects who had not received any 2-dose priming influenza immunization in any previous year - or the the Fluarix-Unprimed Group) received 2 doses of Fluarix™ vaccine at Days 0 and 28. The Fluarix™ vaccine was administered intramuscularly in the deltoid of the right arm.	Biological: Fluarix™; Intramuscular injection

Outcome Measures

Primary Outcome Measures :

1. Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the 3 Fluarix Vaccine Strains. [ Time Frame: At Day 0 [PRE] and at 28 days post last vaccination (Day 28 or Day 56) [POST] ]
   Titers are presented as geometric mean titers (GMTs). The reference cut-off value was 1:10. The 3 influenza strains assessed were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2) and Flu B/Brisbane/60/08 Victoria (VICT).The POST results were the primary outcome variables.

Secondary Outcome Measures :

1. Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease. [ Time Frame: At Days 0 and 28. ]
   Titers are presented as geometric mean titers (GMTs). The reference cut-off value was 1:10. The 4 influenza strains assessed were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the primed groups.
2. Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease. [ Time Frame: At Days 0, 28 and Day 56 ]
   Titers are presented as geometric mean titers (GMTs). The reference cut-off value was 1:10. The 4 influenza strains assessed were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the unprimed groups.
3. Number of Seropositive Subjects Against 4 Strains of Influenza Disease. [ Time Frame: At Days 0 and 28 ]
   A seropositive subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:10. The 4 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the primed groups.
4. Number of Seropositive Subjects Against 4 Strains of Influenza Disease. [ Time Frame: At Days 0, 28 and 56 ]
   A seropositive subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:10. The 4 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the unprimed groups.
5. Number of Seroconverted Subjects Against 4 Strains of Influenza Disease. [ Time Frame: At Day 28 ]
   A seroconverted subject was defined as a vaccinated subject who had 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 four-fold increase in post-vaccination titer. The 4 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the primed groups.
6. Number of Seroconverted Subjects Against 4 Strains of Influenza Disease. [ Time Frame: At Days 28 and 56 ]
   A seroconverted subject was defined as a vaccinated subject who had 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 four-fold increase in post-vaccination titer. The 4 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the unprimed groups.
7. Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease. [ Time Frame: At Day 28 ]
   The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0. The 4 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the primed groups.
8. Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease. [ Time Frame: At Days 28 and 56 ]
   The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0. The 4 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the unprimed groups.
9. Number of Seroprotected Subjects Against 4 Strains of Influenza Disease. [ Time Frame: At Days 0 and 28 ]
   A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. The 4 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the primed groups.
10. Number of Seroprotected Subjects Against 4 Strains of Influenza Disease. [ Time Frame: At Days 0, 28 and 56 ]
    A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. The 4 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the unprimed groups.
11. Number of Subjects With Any and Grade 3 Solicited Local Symptoms. [ Time Frame: During the 7-day follow-up period (Days 0 to 6) after any vaccination ]
    Assessed solicited local symptoms were pain, redness and swelling at the injection site. 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.
12. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. [ Time Frame: During the 7-day follow-up period (Days 0 to 6) after any vaccination ]
    Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature (defined as axillary temperature equal to or above 37.5 degrees Celsius). For other symptoms: Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms assessed by the investigator as related to vaccination. Grade 3 drowsiness = prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 irritability= crying that could not be comforted/prevented normal activity. Grade 3 temperature: ≥ 39.0°C.
13. Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs). [ Time Frame: During the 28-day follow-up period (Days 0 to 27) after vaccination ]
    An unsolicited AE covers any untoward medical occurrence in a 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 = occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to vaccination.
14. Number of Subjects With Any and Related Serious Adverse Events (SAEs). [ Time Frame: From Day 0 to Day 180 (study conclusion) ]
    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. Any was defined as occurrence of any symptom regardless of intensity grade and related was an event assessed by the investigator as causally related to the study vaccination.
15. Number of Subjects With Any Adverse Events of Specific Interest (AESIs). [ Time Frame: From Day 0 to Day 180 (study conclusion) ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Months to 47 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

For all subjects:

• Subjects who the investigator believes that they and/or their Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol.
• Written informed consent obtained from the subject/from the LAR(s).

For unprimed subjects:

• A male or female child aged 18 to 47 months at the time of the first vaccination.
• Children who did not have influenza vaccine in a previous season.

For primed subjects from study NCT00764790:

• Children who received Fluarix™ in the 111751 study NCT00764790.

Exclusion Criteria:

• Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• History of hypersensitivity to any vaccine.
• History of allergy or reactions likely to be exacerbated by any component of the vaccine.
• Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting one month before and ending 28 days after each dose of vaccine(s).
• Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history and physical examination.
• Acute disease at the time of enrolment.
• History of Guillain Barré syndrome within 6 weeks of receipt of prior inactivated influenza virus vaccine.
• Receipt of another seasonal influenza vaccine outside of this study, during current (2009-2010) flu season.
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccination Inhaled and topical steroids are allowed.
• Administration of immunoglobulins and/or blood products within the 3 month preceding the first dose of study vaccine or planned administration during the study period.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.

Contacts and Locations

Locations

Mexico

GSK Investigational Site

Ecatepec de Morelos, Estado De México, Mexico, 55075

GSK Investigational Site

Mexico city, Mexico, 04530

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. 

Study Data/Documents: Informed Consent Form 

Identifier: 113237
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: 113237
For additional information about this study please refer to the GSK Clinical Study Register

Statistical Analysis Plan 

Identifier: 113237
For additional information about this study please refer to the GSK Clinical Study Register

Clinical Study Report 

Identifier: 113237
For additional information about this study please refer to the GSK Clinical Study Register

Individual Participant Data Set 

Identifier: 113237
For additional information about this study please refer to the GSK Clinical Study Register

Study Protocol 

Identifier: 113237
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rodriguez Weber MA, Claeys C, Aranza Doniz C, Feng Y, Innis BL, Jain VK, Peeters M. Immunogenicity and safety of inactivated quadrivalent and trivalent influenza vaccines in children 18-47 months of age. Pediatr Infect Dis J. 2014 Dec;33(12):1262-9. doi: 10.1097/INF.0000000000000463.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00985790
• Other Study ID Numbers: 113237
• First Posted: September 28, 2009
• Results First Posted: March 12, 2013
• Last Update Posted: September 21, 2018
• Last Verified: September 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:

vaccine; Influenza

Additional relevant MeSH terms:

Influenza, Human; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases