A Dose Ranging Safety and Immunogenicity Study of GlaxoSmithKline (GSK) Biologicals' GSK1557484A Vaccine in Children 6 to Less Than 36 Months of Age

NCT02719743 | Completed Phase 2 Results

• 2 other identifiers: 1169382015-003458-42
• Study Type: interventional
• Target: 185
• Locations: 2 countries
• Sites: 7

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.

Conditions

Influenza

Keywords

children; H5N1; observer-blind; Influenza; dose-ranging

Outcome Measures

Primary Outcomes (6)

• Humoral Immune Response for A/Indonesia/05/2005 (H5N1) Strain in Terms of Vaccine-homologous Haemagglutination Inhibition (HI) Antibody Titers Following Primary Vaccination

  The HI antibody titres were expressed in terms of immunogenicity indices for each group. Immunogenicity index (DGMT) = If the LL of the 95% CI for GMT group ratio is less than 0.25 then DGMT =0. If the LL of the 95% CI for GMT group ratio is greater than 1 then DGMT =1.

  At Day 42

• Humoral Immune Response for A/Indonesia/05/2005 (H5N1) Strain in Terms of Vaccine-homologous Microneutralization (MN) Antibody Titers Following Primary Vaccination

  The MN antibody titres were expressed in terms of immunogenicity indices for each group. Immunogenicity index (DGMT) = If the LL of the 95% CI for GMT group ratio is less than 0.25 then DGMT =0. If the LL of the 95% CI for GMT group ratio is greater than 1 then DGMT =1.

  At Day 42

• Evaluation of Fever Index for A/Indonesia/05/2005 (H5N1) Strain in Terms of Vaccine-homologous Haemagglutination Inhibition (HI) Antibody Titers Following Primary Vaccination.

  Fever index was defined as the average temperature for each vaccine group. Fever index (DR) = The average temperature measurement for each vaccine group. Fever index from Days 0-2 after each dose Any temperature \< 38°C (100.4 F) was assigned a value of 0. Any temperature \> 40.5°C was assigned a value of 40.5. DR correspond to 243 minus the sum of recorded temperature values for 3 days after (dose 1 and dose 2)/243.

  During the 3-day follow-up period (i.e. on the day of vaccination and 2 subsequent days) after Dose 1 and Dose 2.

• Evaluation of Fever Index for A/Indonesia/05/2005 (H5N1) Strain in Terms of Vaccine-homologous Microneutralization (MN) Antibody Titers Following Primary Vaccination.

  Fever index was defined as the average temperature for each vaccine group. Fever index (DR)= The average temperature measurement for each vaccine group. Fever index from Days 0-2 after each dose Any temperature \< 38°C (100.4 F) was assigned a value of 0. Any temperature \> 40.5°C was assigned a value of 40.5. DR correspond to 243 minus the sum of recorded temperature values for 3 days after (dose 1 and dose 2)/243.

  During the 3-day follow-up period (i.e. on the day of vaccination and 2 subsequent days) after Dose 1 and Dose 2.

• Mean Geometric Increase (MGI) for Vaccine Homologous and Heterologous HI Antibody Titers Against Each of the Four Vaccine Influenza Strains.

  MGI was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer (Day 392) to the pre-vaccination (Day 385) reciprocal HI titer for the vaccine virus. The vaccine strains assessed were Flu A/Indonesia/5/2005 H5N1 (homologous), Flu A/Vietnam/1194/2004 H5N1 (heterologous), Flu A/duck/Bangladesh/19097/2013 H5N1 (heterologous) and Flu A/gyrfalcon/Washington/41088-6/2014 H5N8 (heterologous).

  At Day 392 (relative to Day 385) post booster vaccination

• Mean Geometric Increase (MGI) for Vaccine Homologous and Heterologous MN Antibody Titers Against Each of the 3 Vaccine Influenza Strains.

  MGI was defined as the geometric mean of the within-subject ratios of the post-vaccination (Day 392) reciprocal MN titer to the pre-vaccination (Day 385) reciprocal MN titer for the vaccine virus. The vaccine strains assessed were Flu A/Indonesia/5/2005 H5N1 (homologous), Flu A/Vietnam /1194/2004 H5N (heterologous) and Flu A/duck/Bangladesh/19097/2013 H5N1 (heterologous).

  At Day 392 (relative to Day 385) post booster vaccination

Secondary Outcomes (18)

• Number of Seroconverted Subjects for HI Antibodies Against Each of the 4 Vaccine Influenza Strains.

  At Days 42, 385 and 392

• Number of Subjects Who Were Seroprotected for HI Antibodies Against Each of the 4 Vaccine Influenza Strains.

  At Days 0, 42, 385, 392

• Geometric Mean Titers (GMTs) for Humoral Immune Response in Terms of HI Antibodies Against Vaccine-homologous/Heterologous Antigens

  At Days 0, 42 and 385 (post the primary immunization), at Day 392 (7 days post booster dose)

• Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the 4 Vaccine Influenza Strains

  At Day 42 (relative to Day 0), at Day 385 (relative to Day 0) and at Day 392 (relative to Day 0)

• Mean Geometric Increase (MGI) for MN Antibodies Against the 3 Vaccine Influenza Strains.

  At Day 385 (relative to Day 0)

Study Arms (5)

H5N1 Formulation 1 Group

ACTIVE COMPARATOR

Subjects received 2 primary doses (adjuvanted) at Days 0 and 21 of H5N1 vaccine Formulation 1 and a booster dose (unadjuvanted) at Day 385 of H5N1 vaccine (GSK1557484A). All doses were administered intramuscularly (IM) in anterolateral thigh.

Biological: Influenza A (H5N1) Virus monovalent vaccine (GSK1557484A).

H5N1 Formulation 2 Group

EXPERIMENTAL

Subjects received 2 primary doses (adjuvanted) at Days 0 and 21 of H5N1 vaccine Formulation 2 and a booster dose (unadjuvanted) at Day 385 of H5N1 vaccine (GSK1557484A). All doses were administered IM in anterolateral thigh.

Biological: Influenza A (H5N1) Virus monovalent vaccine (GSK1557484A).

H5N1 Formulation 3 Group

EXPERIMENTAL

Subjects received 2 primary doses (adjuvanted) at Days 0 and 21 of H5N1 vaccine Formulation 3 and a booster dose (unadjuvanted) at Day 385 of H5N1 vaccine (GSK1557484A). All doses were administered IM in anterolateral thigh.

Biological: Influenza A (H5N1) Virus monovalent vaccine (GSK1557484A).

H5N1 Formulation 4 Group

EXPERIMENTAL

Subjects received 2 primary doses (adjuvanted) at Days 0 and 21 of H5N1 vaccine Formulation 4 and a booster dose (unadjuvanted) at Day 385 of H5N1 vaccine (GSK1557484A). All doses were administered IM in anterolateral thigh.

Biological: Influenza A (H5N1) Virus monovalent vaccine (GSK1557484A).

H5N1 Formulation 5 Group

EXPERIMENTAL

Subjects received 2 primary doses (adjuvanted) at Days 0 and 21 of H5N1 vaccine Formulation 5 and a booster dose (unadjuvanted) at Day 385 of H5N1 vaccine (GSK1557484A). All doses were administered IM in anterolateral thigh.

Biological: Influenza A (H5N1) Virus monovalent vaccine (GSK1557484A).

Interventions

Influenza A (H5N1) Virus monovalent vaccine (GSK1557484A). BIOLOGICAL

All subjects will receive intramuscularly a two-dose primary series (adjuvanted) at a 21 day interval, and a booster dose (unadjuvanted) at Day 385 of GSK1557484A vaccine.

H5N1 Formulation 1 Group; H5N1 Formulation 2 Group; H5N1 Formulation 3 Group; H5N1 Formulation 4 Group; H5N1 Formulation 5 Group

Eligibility Criteria

• Age: 6 Months - 35 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (7)

GSK Investigational Site

Taichung, 404, Taiwan

Location

GSK Investigational Site

Taichung, 407, Taiwan

Location

GSK Investigational Site

Taipei, 100, Taiwan

Location

GSK Investigational Site

Taipei, 104, Taiwan

Location

GSK Investigational Site

Taoyuan District, 333, Taiwan

Location

GSK Investigational Site

Bangkok, 10330, Thailand

Location

GSK Investigational Site

Chiang Mai, 50200, Thailand

Location

Related Publications (1)

• 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.

  PMID: 34285165 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

pandemrix

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

ct427449@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2016
• First Posted: March 25, 2016
• Study Start: July 7, 2016
• Primary Completion: February 13, 2018
• Study Completion: February 13, 2018
• Last Updated: June 27, 2019
• Results First Posted: June 3, 2019

Record last verified: 2019-06

Locations

TW (5); TH (2)