Immunogenicity and Safety Study of Different Formulations of GlaxoSmithKline (GSK) Biologicals H7N1 Influenza Vaccine Administered to Adults 21 to 64 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 H7N1 influenza vaccine in subjects 21 to 64 years of age. The study will evaluate safety related events and antibody immune responses to different formulations of study vaccine and placebo.

Official Title
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An Observer-blind Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Influenza Vaccine(s) GSK2789869A and GSK2789868A Administered in Adults 21 to 64 Years of Age

Conditions
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Influenza

Intervention / Treatment
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* Biological: Investigational H7N1 vaccine GSK2789869A
* Biological: Investigational H7N1 vaccine GSK2789868A
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adults who are 21 to 64 years of age (inclusive) at the time of first study vaccination. Written informed consent obtained from the 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, which may be either in the home or at the workplace, land line or mobile, but NOT a pay phone or other multiple-user device. For subjects who undergo a screening visit, results of all safety laboratory tests obtained at the screening visit must be within reference ranges. Results of any repeat testing cannot be used to qualify a subject for enrollment. Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as current tubal ligation, hysterectomy, ovariectomy or post-menopause. 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. Persons with a history of cancer who are disease-free without treatment for three years or more are eligible. Persons with a history of histologically-confirmed basal cell carcinoma of the skin successfully treated with local excision only are excepted and are eligible, but other histologic types of skin cancer are exclusionary. Women who are disease-free three years or more after treatment for breast cancer and receiving long-term prophylaxis are eligible. Diagnosed with excessive daytime sleepiness (unintended sleep episodes during the day present almost daily for at least one month), or narcolepsy. History of narcolepsy in 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. NOTE: The subject may be vaccinated at a later date, provided symptoms have resolved, and all other eligibility criteria continue to be satisfied. 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. Topical, intra-articularly injected, or inhaled glucocorticoids, topical calcineurin inhibitors or imiquimod are allowed. Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. Persons receiving individual doses of low molecular weight heparin outside of 24 hours prior to vaccination are eligible. Persons receiving prophylactic antiplatelet medications, e.g., low-dose aspirin, and without a clinically-apparent bleeding tendency, are eligible. 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: 21 Years
Maximum Age: 64 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 GSK2789869A H7N1 vaccine formulation 1 at a 21 day interval | Biological: Investigational H7N1 vaccine GSK2789869A<br>* One dose of GSK2789869A H7N1 vaccine administered intramuscularly at the deltoid region of the non-dominant arm at Day 0 while second dose of GSK2789869A H7N1 vaccine administered intramuscularly at the deltoid region of the dominant arm at Day 21<br>|
| Experimental: Formulation 2 Group<br>Subjects in this group will receive two doses of GSK2789869A H7N1 vaccine formulation 2 at a 21 day interval | Biological: Investigational H7N1 vaccine GSK2789869A<br>* One dose of GSK2789869A H7N1 vaccine administered intramuscularly at the deltoid region of the non-dominant arm at Day 0 while second dose of GSK2789869A H7N1 vaccine administered intramuscularly at the deltoid region of the dominant arm at Day 21<br>|
| Experimental: Formulation 3 Group<br>Subjects in this group will receive two doses of GSK2789869A H7N1 vaccine formulation 3 at a 21 day interval | Biological: Investigational H7N1 vaccine GSK2789869A<br>* One dose of GSK2789869A H7N1 vaccine administered intramuscularly at the deltoid region of the non-dominant arm at Day 0 while second dose of GSK2789869A H7N1 vaccine administered intramuscularly at the deltoid region of the dominant arm at Day 21<br>|
| Experimental: Formulation 4 Group<br>Subjects in this group will receive two doses of GSK2789869A H7N1 vaccine formulation 4 at a 21 day interval | Biological: Investigational H7N1 vaccine GSK2789869A<br>* One dose of GSK2789869A H7N1 vaccine administered intramuscularly at the deltoid region of the non-dominant arm at Day 0 while second dose of GSK2789869A H7N1 vaccine administered intramuscularly at the deltoid region of the dominant arm at Day 21<br>|
| Experimental: Formulation 5 Group<br>Subjects in this group will receive two doses of GSK2789868A H7N1 vaccine formulation 5 at a 21 day interval | Biological: Investigational H7N1 vaccine GSK2789868A<br>* One dose of GSK2789868A H7N1 vaccine administered intramuscularly at the deltoid region of the non-dominant arm at Day 0 while the second dose of GSK2789868A H7N1 vaccine administered intramuscularly at the deltoid region of the 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 intramuscularly at the deltoid region of the non-dominant arm at Day 0 while the second dose of placebo administered intramuscularly at the deltoid region of the 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 for each adjuvanted H7N1 vaccine group | The following aggregate variables will be calculated: Seroconversion rates (SCR); Seroprotection rates (SPR); Mean Geometric Increase (MGI); | 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 |  | From Day 0 - 42 after each vaccination (i.e Days 0, 7 , 21, 28, 42) | 
| Occurrence of unsolicited adverse events |  | 21 days after each dose | 
| Occurrence of Medically Attended Adverse Events (MAEs), potential Immune Mediated Diseases (pIMDs) and Serious Adverse Events (SAEs) |  | From Day 0 until the Day 42 visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral immune response in terms of Geometric mean reciprocal serum HI antibody titers (GMTs ratios) | GMT ratios will be calculated for each adjuvanted (GSK2789869A) vaccine group which successfully meets Center for Biologics Evaluation and Research (CBER) and Committee for Medicinal Products for Human Use (CHMP) criteria, and for the unadjuvanted (GSK2789868A) plain antigen vaccine group | At Day 42 | 
| Humoral immune response in terms of vaccine-homologous HI antibody titers for the unadjuvanted (GSK2789868A) plain antigen vaccine group | The following aggregate variables will be calculated : • SCR; • SPR; • MGI; | At Day 42 | 
| Vaccine-homologous (H7N1) HI antibody titers | The following aggregate variables will be calculated for each study group: • GMTs; • Seropositivity rates; • SCR; • SPR; • MGI; | • GMTs and Seropositivity rates at Days 0, 21, 42 and Months 6 and 12. • SCR and MGI at Day 21, 42 (Placebo group only) and Months 6 and 12. • SPR at Days 0, 21, 42 (Placebo group only) and Months 6 and 12. | 
| Vaccine-homologous (H7N1) HI antibody titers by age stratum | The following aggregate variables will be calculated for each study group by age stratum (21-40 years; 41-64 years): • GMTs; • Seropositivity rates; • SCR; • SPR; • MGI; | • GMTs, Seropositivity rates and SPR at Days 0, 21, 42 and Months 6 and 12. • SCR and MGI at Day 21, 42 and Months 6 and 12. | 
| Vaccine-heterologous (H7N9) HI antibody titers |  | • GMTs and Seropositivity rates and SPR at Days 0, 21, 42 and Months 6 and 12. • SCR and MGI at Day 21, 42 and Months 6 and 12. | 
| Vaccine homologous (H7N1) and heterologous (H7N9) neutralizing (MN) antibody titers |  | • 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 |  | After the Day 42 visit until the Month 12 visit | 
| Humoral immune response in terms of SCR difference | SCR difference will be calculated for each adjuvanted (GSK2789869A) vaccine group which successfully meets CBER and CHMP criteria, and for the unadjuvanted (GSK2789868A) plain antigen vaccine group | At Day 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity, H7N1, Influenza, Safety, AS03 adjuvant, Adults