Immunogenicity and Safety Study of Different Formulations of GlaxoSmithKline (GSK) Biologicals H7N1 Influenza Vaccine Administered to Adults 21 to 64 Years of Age

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

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Investigational H7N1 vaccine GSK2789869A; Biological: Investigational H7N1 vaccine GSK2789868A; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 427
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Truro, Nova Scotia, Canada, B2N 1L2
      • GSK Investigational Site
  • Ontario
    • Sudbury, Ontario, Canada, P3E 1H5
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M9W 4L6
      • GSK Investigational Site
• United States
  • Florida
    • Miami, Florida, United States, 33143
      • GSK Investigational Site
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • GSK Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • GSK Investigational Site
  • New York
    • Rochester, New York, United States, 14609
      • GSK Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78705
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

  1. Persons with a history of cancer who are disease-free without treatment for three years or more are eligible.
  2. 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.
  3. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Formulation 1 Group; Subjects in this group will receive two doses of GSK2789869A H7N1 vaccine formulation 1 at a 21 day interval	Biological: Investigational H7N1 vaccine GSK2789869A; 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
Experimental: Formulation 2 Group; Subjects in this group will receive two doses of GSK2789869A H7N1 vaccine formulation 2 at a 21 day interval	Biological: Investigational H7N1 vaccine GSK2789869A; 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
Experimental: Formulation 3 Group; Subjects in this group will receive two doses of GSK2789869A H7N1 vaccine formulation 3 at a 21 day interval	Biological: Investigational H7N1 vaccine GSK2789869A; 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
Experimental: Formulation 4 Group; Subjects in this group will receive two doses of GSK2789869A H7N1 vaccine formulation 4 at a 21 day interval	Biological: Investigational H7N1 vaccine GSK2789869A; 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
Experimental: Formulation 5 Group; Subjects in this group will receive two doses of GSK2789868A H7N1 vaccine formulation 5 at a 21 day interval	Biological: Investigational H7N1 vaccine GSK2789868A; 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
Placebo Comparator: Placebo Group; Subjects in this group will receive two doses of placebo at a 21 day interval	Biological: Placebo; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Madan A, Ferguson M, Sheldon E, Segall N, Chu L, Toma A, Rheault P, Friel D, Soni J, Li P, Innis BL, Schuind A. Immunogenicity and safety of an AS03-adjuvanted H7N1 vaccine in healthy adults: A phase I/II, observer-blind, randomized, controlled trial. Vaccine. 2017 Mar 7;35(10):1431-1439. doi: 10.1016/j.vaccine.2017.01.054. Epub 2017 Feb 7.

Helpful Links

• 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 record dates

Study Major Dates

• Study Start (Actual): August 26, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): October 20, 2014

Study Registration Dates

• First Submitted: August 1, 2013
• First Submitted That Met QC Criteria: August 29, 2013
• First Posted (Estimate): September 4, 2013

Study Record Updates

• Last Update Posted (Actual): May 8, 2017
• Last Update Submitted That Met QC Criteria: May 4, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Influenza; Adults; Immunogenicity; H7N1; AS03 adjuvant
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 115415

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.

Study Data/Documents

1. Informed Consent Form
   Information identifier: 115415
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: 115415
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 115415
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 115415
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 115415
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 115415
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register