Clinical trial NCT02719743: A Dose Ranging Safety and Immunogenicity Study of GlaxoSmithKline (GSK) Biologicals' GSK1557484A Vaccine in Children 6 to Less Than 36 Months of Age
Official title: An Observer-blind, Dose Ranging Safety and Immunogenicity Study of GSK Biologicals' GSK1557484A Vaccine in Children 6 to Less Than 36 Months of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Keywords: children
H5N1
observer-blind
Influenza
dose-ranging
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-03-25
Enrollment: 185
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the safety and immunogenicity of different formulations of GSK Biologicals' influenza candidate vaccine GSK1557484A, in children 6-35 months of age.

Detailed description: Safety and immunogenicity of different formulations administered as a 2-dose schedule in children 6-35 months of age will be evaluated. In addition, the quality of the 2-dose priming will be assessed through the anamnestic response elicited by an antigen challenge (unadjuvanted H5N1) administered 12 months later. The persistence of the immune response approximately 12 months (Day 385) after dose 2 will also be evaluated.

Subjects from each group will be enrolled into the CMI sub-cohort comprising of approximately 100 subjects. Within the participating country(ies), these subjects will be enrolled in only selected/qualified sites.

Eligibility criteria: Inclusion Criteria:

* Subject's parent(s)/ Legally Acceptable Representative(s) \[LAR(s)\] who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* Male or female children 6 months to less than 36 months old at the time of the first vaccination. Children who are not 36 months old as of Day 0, the day of first vaccine dose under this protocol, can be enrolled.
* Written informed consent obtained from the parent(s)/legally acceptable representative(s) \[LAR(s)\] of the subject prior to performance of any study specific procedure.
* Healthy subjects as established by medical history and standard physical examination before entering into the study.
* Born full-term to be confirmed by interview with parent/LAR or available medical records.

Exclusion Criteria:

* Child in care.
* Medical history of physician-confirmed infection with an H5N1 virus.
* Previous vaccination at any time with an H5N1 vaccine.
* Concurrently participating in another clinical study, or use of an investigational or a non-registered vaccine, pharmaceutical product, or device within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Presence in the parent(s) / LAR(s) of evidence of substance abuse or of neurological or psychiatric diagnoses which, even if stable, are deemed by the investigator to render the parent(s)/LAR(s) unable/unlikely to provide accurate safety reports.
* Acute disease and/or fever at the time of enrolment.
* Administration of immunoglobulins, any blood products, or long-acting immune-modifying drugs during the period starting 3 months before the first dose of study vaccine, or planned administration during the study period.
* History of any neurological disorders or seizures, or Guillain-Barré Syndrome.
* Diagnosed with excessive daytime sleepiness or narcolepsy; or history of narcolepsy in a subject's parent or sibling.
* Administration of an inactive vaccine within 14 days or of a live attenuated vaccine within 30 days before the first vaccination.
* Planned administration of any vaccine not foreseen by the study protocol between Day 0 and Day 42 or planned administration of an inactive vaccine within 14 days or of a live attenuated vaccine within 30 days before through 30 days after the booster vaccination. Note: routine vaccinations may be provided on Day 42 after all study assessments have been performed.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine; a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.
* Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
* Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine. For corticosteroids, this will mean a dose of prednisone or equivalent of \> 2 mg/kg/day of body weight or ≥ 20 mg/day (for persons who weigh ≥ 10 kg). Inhaled and topical steroids are allowed.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Family history of congenital or hereditary immunodeficiency.
* Major congenital defects.
* Any condition which, in the opinion of the investigator, prevents the subject from participating in the study.

Primary outcomes:
measure: Humoral Immune Response for A/Indonesia/05/2005 (H5N1) Strain in Terms of Vaccine-homologous Haemagglutination Inhibition (HI) Antibody Titers Following Primary Vaccination
timeFrame: At Day 42
measure: Humoral Immune Response for A/Indonesia/05/2005 (H5N1) Strain in Terms of Vaccine-homologous Microneutralization (MN) Antibody Titers Following Primary Vaccination
timeFrame: At Day 42
measure: Evaluation of Fever Index for A/Indonesia/05/2005 (H5N1) Strain in Terms of Vaccine-homologous Haemagglutination Inhibition (HI) Antibody Titers Following Primary Vaccination.
timeFrame: During the 3-day follow-up period (i.e. on the day of vaccination and 2 subsequent days) after Dose 1 and Dose 2.
measure: Evaluation of Fever Index for A/Indonesia/05/2005 (H5N1) Strain in Terms of Vaccine-homologous Microneutralization (MN) Antibody Titers Following Primary Vaccination.
timeFrame: During the 3-day follow-up period (i.e. on the day of vaccination and 2 subsequent days) after Dose 1 and Dose 2.
measure: Mean Geometric Increase (MGI) for Vaccine Homologous and Heterologous HI Antibody Titers Against Each of the Four Vaccine Influenza Strains.
timeFrame: At Day 392 (relative to Day 385) post booster vaccination
measure: Mean Geometric Increase (MGI) for Vaccine Homologous and Heterologous MN Antibody Titers Against Each of the 3 Vaccine Influenza Strains.
timeFrame: At Day 392 (relative to Day 385) post booster vaccination
Secondary outcomes:
measure: Number of Seroconverted Subjects for HI Antibodies Against Each of the 4 Vaccine Influenza Strains.
timeFrame: At Days 42, 385 and 392
measure: Number of Subjects Who Were Seroprotected for HI Antibodies Against Each of the 4 Vaccine Influenza Strains.
timeFrame: At Days 0, 42, 385, 392
measure: Geometric Mean Titers (GMTs) for Humoral Immune Response in Terms of HI Antibodies Against Vaccine-homologous/Heterologous Antigens
timeFrame: At Days 0, 42 and 385 (post the primary immunization), at Day 392 (7 days post booster dose)
measure: Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the 4 Vaccine Influenza Strains
timeFrame: At Day 42 (relative to Day 0), at Day 385 (relative to Day 0) and at Day 392 (relative to Day 0)
measure: Mean Geometric Increase (MGI) for MN Antibodies Against the 3 Vaccine Influenza Strains.
timeFrame: At Day 385 (relative to Day 0)
measure: Humoral Immune Response for A/Indonesia/05/2005 (H5N1) Strain in Terms of MN Antibodies Against Vaccine-homologous/Heterologous Antigens
timeFrame: At Days 0, 42, 385 and Day 392
measure: Vaccine Response Rate (VRR) for Homologous and Heterologous MN Antibodies Against Each of the 3 Vaccine Influenza Strains.
timeFrame: At Day 42, Day 385 (relative to Day 0), Day 392 (relative to Day 0) and D 392 (relative to Day 385)
measure: Cell Mediated Immunity (CMI) in Terms of T-cell Markers Related to Flu A/Indonesia/05/2005 Antigen.
timeFrame: At Days 0, 42, 385 and 392
measure: Number of Subjects Reporting Solicited Local Symptoms
timeFrame: During the 7-day follow-up period (i.e. on the day of vaccination and 6 subsequent days) after any vaccine dose
measure: Duration of Solicited Local Symptoms
timeFrame: During the 7-day follow-up period (i.e. on the day of vaccination and 6 subsequent days) after any vaccine dose
measure: Number of Subjects Reporting Solicited General Symptoms.
timeFrame: During the 7-day follow-up period (i.e. on the day of vaccination and 6 subsequent days) after any vaccine dose
measure: Duration of Solicited General Symptoms.
timeFrame: During the 7-day follow-up period (i.e. on the day of vaccination and 6 subsequent days) after any vaccine dose
measure: Number of Subjects Reporting Any Unsolicited Adverse Events (AEs) Post Primary Vaccination.
timeFrame: During the 21-day follow-up period (Day 0-Day 20) after each vaccine dose
measure: Number of Subjects Reporting Any Unsolicited Adverse Events (AEs) Post Booster Vaccination
timeFrame: During the 30-day (Day 385-Day 415) follow-up period after vaccination
measure: Number of Subjects Reporting Medically Attended Events (MAEs)
timeFrame: During the entire study period (Day 0 to Day 415 approximately)
measure: Number of Subjects Reporting Potential Immune Mediated Diseases (pIMDs)
timeFrame: During the entire study period (Day 0 to Day 415 approximately)
measure: Number of Subjects Reporting Serious Adverse Events (SAEs)
timeFrame: During the entire study period (Day 0 to Day 415 approximately)
measure: Number of Subjects Reporting Adverse Events of Special Interest (AESI)
timeFrame: During the entire study period (Day 0 to Day 415 approximately)
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: GSK Investigational Site
city: Taichung
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taoyuan
country: Taiwan
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Chiang Mai
country: Thailand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kim JH, Drame M, Puthanakit T, Chiu NC, Supparatpinyo K, Huang LM, Chiu CH, Chen PY, Hwang KP, Danier J, Friel D, Salaun B, Woo W, Vaughn DW, Innis B, Schuind A. Immunogenicity and Safety of AS03-adjuvanted H5N1 Influenza Vaccine in Children 6-35 Months of Age: Results From a Phase 2, Randomized, Observer-blind, Multicenter, Dose-ranging Study. Pediatr Infect Dis J. 2021 Sep 1;40(9):e333-e339. doi: 10.1097/INF.0000000000003247.