Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Influenza Vaccine(s) GSK3277510A and GSK3277509A in Adults 18 to 60 Years of Age

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and immunogenicity of different formulations of GSK Biologicals' H7N9 influenza vaccine in subjects 18 to 60 years of age.

Official Title
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An Observer-blind Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Influenza Vaccine(s) GSK3277510A and GSK3277509A Administered in Adults 18 to 60 Years of Age

Conditions
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Influenza

Intervention / Treatment
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* Biological: Investigational H7N9 vaccine GSK3277510A
* Biological: Investigational H7N9 vaccine GSK3277509A
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adults who are 18 to 60years of age (inclusive) at the time of first study vaccination. Written informed consent obtained from subject. Subjects who the investigator believes can and will comply with the requirements of the protocol. Healthy subjects as established by medical history and physical examination. Access to a consistent means of telephone contact. For subjects who undergo a screening visit: Results of screening safety laboratory tests that figure in eligibility assessment must be within reference ranges before dosing. Female subjects of non-childbearing potential may be enrolled in the study. Female subjects of childbearing potential may be enrolled in the study, if they have practiced adequate contraception for 30 days prior to vaccination, and have a negative pregnancy test on the day of vaccination, and agree to continue to practice adequate contraception until 2 months after the last dose administered. Exclusion Criteria: Presence or evidence of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports. Presence or evidence of substance abuse. Diagnosed with cancer, or treatment for cancer within three years. Diagnosed with excessive daytime sleepiness, or narcolepsy; or history of narcolepsy in a subject's parent, sibling or child. Presence of a temperature ≥ 38.0ºC (≥100.4ºF), or acute symptoms greater than mild severity on the scheduled date of first vaccination. Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection. Receipt of systemic glucocorticoids within 30 days prior to the first dose of study vaccine/placebo, or any other cytotoxic, immunosuppressive or immune-modifying drugs within 6 months of first study vaccine/ placebo dose. Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. An acute evolving neurological disorder or Guillain Barré Syndrome within 42 days of receipt of prior seasonal or pandemic influenza vaccine. Administration of an inactive vaccine within 14 days or of a live attenuated vaccine within 30 days before the first dose of study vaccine/placebo. Planned administration of any vaccine other than the study vaccine/placebo before blood sampling at the Day 42 visit. Previous administration of any H7 vaccine or physician-confirmed H7 disease. Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine/placebo, or planned use during the study period. Receipt of any immunoglobulins and/or any blood products within 90 days before the first dose of study vaccine/placebo, or planned administration of any of these products during the study period. Any known or suspected allergy to any constituent of influenza vaccines or component used in the manufacturing process of the study vaccine including a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine. Known pregnancy or a positive urine beta-human chorionic gonadotropin (β-hCG) test result before the first dose of study vaccine/placebo. Lactating or nursing women. Any condition which, in the opinion of the investigator, prevents the subject from participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Formulation 1 Group<br>Subjects in this group will receive two doses of GSK3277510A H7N9 vaccine formulation 1 at a 21 day interval | Biological: Investigational H7N9 vaccine GSK3277510A<br>* One dose of GSK3277510A H7N9 vaccine administered intramuscularly (IM) in the deltoid region of non-dominant arm at Day 0 and the second dose of GSK3277510A H7N9 vaccine administered IM in the deltoid region of dominant arm at Day 21<br>|
| Experimental: Formulation 2 Group<br>Subjects in this group will receive two doses of GSK3277510A H7N9 vaccine formulation 2 at a 21 day interval | Biological: Investigational H7N9 vaccine GSK3277510A<br>* One dose of GSK3277510A H7N9 vaccine administered intramuscularly (IM) in the deltoid region of non-dominant arm at Day 0 and the second dose of GSK3277510A H7N9 vaccine administered IM in the deltoid region of dominant arm at Day 21<br>|
| Experimental: Formulation 3 Group<br>Subjects in this group will receive two doses of GSK3277510A H7N9 vaccine formulation 3 at a 21 day interval | Biological: Investigational H7N9 vaccine GSK3277510A<br>* One dose of GSK3277510A H7N9 vaccine administered intramuscularly (IM) in the deltoid region of non-dominant arm at Day 0 and the second dose of GSK3277510A H7N9 vaccine administered IM in the deltoid region of dominant arm at Day 21<br>|
| Experimental: Formulation 4 Group<br>Subjects in this group will receive two doses of GSK3277510A H7N9 vaccine formulation 4 at a 21 day interval | Biological: Investigational H7N9 vaccine GSK3277510A<br>* One dose of GSK3277510A H7N9 vaccine administered intramuscularly (IM) in the deltoid region of non-dominant arm at Day 0 and the second dose of GSK3277510A H7N9 vaccine administered IM in the deltoid region of dominant arm at Day 21<br>|
| Experimental: Formulation 5 Group<br>Subjects in this group will receive two doses of GSK3277509A H7N9 vaccine formulation 5 at a 21 day interval | Biological: Investigational H7N9 vaccine GSK3277509A<br>* One dose of GSK3277509A H7N9 vaccine administered IM at the deltoid region of non-dominant arm at Day 0 and the second dose of GSK3277509A H7N9 vaccine administered IM at the deltoid region of dominant arm at Day 21<br>|
| Placebo Comparator: Placebo Group<br>Subjects in this group will receive two doses of placebo at a 21 day interval | Biological: Placebo<br>* One dose of placebo administered IM at the deltoid region of non-dominant arm at Day 0 and the second dose of placebo administered IM at the deltoid region of dominant arm at Day 21<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral immune response in terms of vaccine-homologous hemagglutination inhibition (HI) antibody titers |  | At Day 42. | 
| Occurrence of each solicited local symptom |  | During a 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after each vaccination. | 
| Occurrence of each solicited general symptom |  | During a 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after each vaccination. | 
| Occurrence of clinical safety laboratory abnormalities reported for samples |  | At the Day 0, 7, 21, 28 and 42 visits. | 
| Occurrence of unsolicited adverse events (AEs) |  | 21 days after each dose. | 
| Occurrence of Medically Attended Adverse Events (MAEs), potential Immune Mediated Diseases (pIMDs) and Serious Adverse Events (SAEs)[Active Phase] |  | From Day 0 until Day 42. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of adjuvant effect as assessed by vaccine-homologous hemagglutination inhibition (HI) antibody titers |  | At Day 42. | 
| Humoral immune response in terms of vaccine-homologous hemagglutination inhibition (HI) antibody titers for plain antigen vaccine group |  | At Day 42. | 
| Humoral immune response in terms of vaccine-homologous (H7N9) HI antibody titers. |  | GMTs and Seropositivity rates at Days 0, 21, 42 and Months 6 and 12. SCR and MGI at Days 21, 42 (Placebo group only) and Months 6 and 12. SPR at Days 0, 21, 42 (Placebo group only) and Months 6 and 12. | 
| Humoral immune response in terms of vaccine-homologous (H7N9) neutralizing (MN) antibody titres. |  | GMTs and Seropositivity rates at the Days 0, 21, 42 and Month 6 visits. VRR at Days 21, 42 and Month 6 visits. | 
| Humoral immune response in terms of vaccine-homologous (H7N9) HI antibody titers by age stratum. |  | GMTs, Seropositivity rates and SPR at Days 0, 21, 42 and Months 6 and 12. SCR and MGI at Days 21, 42 and Months 6 and 12. | 
| Humoral immune response in terms of vaccine homologous (H7N9) neutralizing (MN) antibody titers for each study group by age stratum (18-40 years; 41-60 years) |  | GMTs and Seropositivity rates at Days 0, 21, 42 and Month 6. VRR at Days 21, 42 and Month 6. | 
| Occurrence of MAEs, pIMDs and SAEs |  | Until the Month 12 visit. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adjuvant, Safety, Influenza, H7N9, Immunogenicity, Adults