Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Influenza Vaccine(s) GSK3206641A and GSK3206640A Administered in Adults 18 to 64 Years of Age

An Observer-blind Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Influenza Vaccine(s) GSK3206641A and GSK3206640A Administered in Adults 18 to 64 Years of Age

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 64 years of age.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Investigational H7N9 vaccine GSK3206641A; Biological: Investigational H7N9 vaccine GSK3206640A; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 424
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Truro, Nova Scotia, Canada, B2N 1L2
      • GSK Investigational Site
  • Ontario
    • Woodstock, Ontario, Canada, N4S 5P5
      • GSK Investigational Site
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 2G2
      • GSK Investigational Site
• United States
  • Florida
    • Jacksonville, Florida, United States, 32216
      • GSK Investigational Site
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • GSK Investigational Site
  • Idaho
    • Boise, Idaho, United States, 83642
      • GSK Investigational Site
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16506
      • GSK Investigational Site
  • Washington
    • Seattle, Washington, United States, 98105
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female adults who are 18 to 64 years 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 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 enrolment.
• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• 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 GSK3206641A H7N9 vaccine formulation 1 at a 21 day interval	Biological: Investigational H7N9 vaccine GSK3206641A; One dose of GSK3206641A H7N9 vaccine administered intramuscularly (IM) in the deltoid region of arm at Day 0 and the second dose of GSK3206641A H7N9 vaccine administered IM in the deltoid region of arm at Day 21
EXPERIMENTAL: Formulation 2 Group; Subjects in this group will receive two doses of GSK3206641A H7N9 vaccine formulation 2 at a 21 day interval	Biological: Investigational H7N9 vaccine GSK3206641A; One dose of GSK3206641A H7N9 vaccine administered intramuscularly (IM) in the deltoid region of arm at Day 0 and the second dose of GSK3206641A H7N9 vaccine administered IM in the deltoid region of arm at Day 21
EXPERIMENTAL: Formulation 3 Group; Subjects in this group will receive two doses of GSK3206641A H7N9 vaccine formulation 3 at a 21 day interval	Biological: Investigational H7N9 vaccine GSK3206641A; One dose of GSK3206641A H7N9 vaccine administered intramuscularly (IM) in the deltoid region of arm at Day 0 and the second dose of GSK3206641A H7N9 vaccine administered IM in the deltoid region of arm at Day 21
EXPERIMENTAL: Formulation 4 Group; Subjects in this group will receive two doses of GSK3206641A H7N9 vaccine formulation 4 at a 21 day interval	Biological: Investigational H7N9 vaccine GSK3206641A; One dose of GSK3206641A H7N9 vaccine administered intramuscularly (IM) in the deltoid region of arm at Day 0 and the second dose of GSK3206641A H7N9 vaccine administered IM in the deltoid region of arm at Day 21
EXPERIMENTAL: Formulation 5 Group; Subjects in this group will receive two doses of GSK3206640A H7N9 vaccine formulation 5 at a 21 day interval	Biological: Investigational H7N9 vaccine GSK3206640A; One dose of GSK3206640A H7N9 vaccine administered IM at the deltoid region of arm at Day 0 and the second dose of GSK3206640A H7N9 vaccine administered IM at the deltoid region of 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 IM at the deltoid region of arm at Day 0 and the second dose of placebo administered IM at the deltoid region of arm at Day 21

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 unsolicited adverse events		21 days after each dose
Humoral immune response in terms of vaccine-homologous hemagglutination inhibition (HI) antibody titers	The following aggregate variables will be calculated for each adjuvanted H7N9 vaccine group: • Seroconversion rates (SCR); • Seroprotection rates (SPR); • Mean Geometric Increase (MGI)	At Day 42
Occurrence of clinical safety laboratory abnormalities reported for samples		At Day 0 visit
Occurrence of clinical safety laboratory abnormalities reported for samples		At Day 7 visit
Occurrence of clinical safety laboratory abnormalities reported for samples		At Day 21 visit
Occurrence of clinical safety laboratory abnormalities reported for samples		At Day 28 visit
Occurrence of clinical safety laboratory abnormalities reported for samples		At Day 42 visit
Occurrence of Medically Attended Adverse Events (MAEs), potential Immune Mediated Diseases (pIMDs) and Serious Adverse Events (SAEs)		From Day 0 until the Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Humoral immune response in terms of vaccine-homologous hemagglutination inhibition (HI) antibody titers	The following aggregate variables will be calculated for each adjuvanted (GSK3206641A) vaccine group which successfully meets CBER and CHMP criteria, and for the unadjuvanted (GSK3206640A) plain antigen vaccine group: • Geometric mean reciprocal serum HI antibody titers (GMTs); • SCR	At Day 42
Humoral immune response in terms of vaccine-homologous hemagglutination inhibition (HI) antibody titers	The following aggregate variables will be calculated for the unadjuvanted plain antigen vaccine group: • SCR; • SPR; • MGI	At Day 42
Humoral immune response in terms of vaccine-homologous (H7N9) 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
Humoral immune response in terms of vaccine-homologous (H7N9) HI antibody titers by age stratum	The following aggregate variables will be calculated for each study group by age stratum (18-40 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
Humoral immune response in terms of vaccine homologous (H7N9) neutralizing (MN) antibody titers	The following parameters will be calculated for a subset of subjects in each study group: • GMTs; • Seropositivity rates; • Vaccine response rate (VRR)	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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Madan A, Segall N, Ferguson M, Frenette L, Kroll R, Friel D, Soni J, Li P, Innis BL, Schuind A. Immunogenicity and Safety of an AS03-Adjuvanted H7N9 Pandemic Influenza Vaccine in a Randomized Trial in Healthy Adults. J Infect Dis. 2016 Dec 1;214(11):1717-1727. doi: 10.1093/infdis/jiw414. Epub 2016 Sep 7.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 25, 2013
• Primary Completion (ACTUAL): February 1, 2014
• Study Completion (ACTUAL): January 19, 2015

Study Registration Dates

• First Submitted: November 21, 2013
• First Submitted That Met QC Criteria: November 26, 2013
• First Posted (ESTIMATE): December 3, 2013

Study Record Updates

• Last Update Posted (ACTUAL): May 30, 2017
• Last Update Submitted That Met QC Criteria: May 26, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Influenza; Adults; Immunogenicity; Adjuvant; H7N9
• 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: 201072

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: 201072
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 201072
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 201072
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: 201072
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Annotated Case Report Form
   Information identifier: 201072
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 201072
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Clinical Study Report
   Information identifier: 201072
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register