Clinical trial NCT01949090: Immunogenicity and Safety Study of Different Formulations of GlaxoSmithKline (GSK) Biologicals H7N1 Influenza Vaccine Administered to Adults 65 Years of Age and Older
Official title: An Observer-blind Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Influenza Vaccine(s) GSK2789869A Administered in Adults 65 Years of Age and Older
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Keywords: H7N1
AS03 adjuvant
Safety
Immunogenicity
Influenza
Adults
Elderly adults
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-09-24
Enrollment: 363
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this placebo controlled study is to evaluate the safety and immunogenicity of different formulations of GSK Biologicals H7N1 influenza vaccine in subjects 65 years of age and older. The study will evaluate safety related events and antibody immune responses to different formulations of study vaccine.


Eligibility criteria: Inclusion Criteria:

* Male or female adults who are 65 years of age and older 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.
* Stable health status, as established by medical history and physical exam, and defined by absence of a health event satisfying the definition of a serious adverse event, or a change in an ongoing drug therapy due to therapeutic failure or symptoms of drug toxicity, within 1 month prior to enrollment.
* 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.

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; or 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.
* 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.
* Any condition which, in the opinion of the investigator, prevents the subject from participating in the study.

Primary outcomes:
measure: Number of Seroconverted (SCR) Subjects for Hemagglutination Inhibition (HI) Antibodies Against the Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain
timeFrame: At Day 42
measure: Number of Subjects Who Were Seroprotected for HI Antibodies Against the Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain
timeFrame: At Day 42
measure: Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain
timeFrame: At Day 42
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values
timeFrame: At Day 0
measure: Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values
timeFrame: At Day 7
measure: Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values
timeFrame: At Day 21
measure: Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values
timeFrame: At Day 28
measure: Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values
timeFrame: At Day 42
measure: Number of Subjects With Any Medically-attended Adverse Events (MAEs)
timeFrame: From Day 0 up to Day 42
measure: Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs)
timeFrame: From Day 0 up to Day 42
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: From Day 0 up to Day 42
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Day 0 up to Day 42
Secondary outcomes:
measure: Number of Subjects With HI Antibody Concentrations Above the Cut-off Value for Vaccine-homologous (H7N1)
timeFrame: At Days 0, 21, 42 and Months 6 and 12
measure: Titers for Antibodies Against Flu A/Mallard/NL/12/2000 Strain of Influenza Disease Vaccine-homologous (H7N1)
timeFrame: At Days 0, 21, 42 and Months 6 and 12
measure: Number of Seroprotected (SPR) Subjects Against HI Antibodies for Vaccine-homologous (H7N1)
timeFrame: At Days 0, 21 and 42 and at Months 6 and 12
measure: Number of Seroconverted (SCR) Subjects for HI Antibodies for Vaccine-homologous (H7N1)
timeFrame: At Days 21 and 42 and at Months 6 and 12
measure: Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/Mallard/NL/12/2000 Strain of Influenza Disease Vaccine-homologous (H7N1)
timeFrame: At Days 21 and 42 and at Months 6 and 12
measure: Number of Subjects With HI Antibody Concentrations Above the Cut-off Value for Vaccine-heterologous (H7N9)
timeFrame: At Days 0, 21 and 42 and at Months 6 and 12
measure: Titers for Antibodies Against Flu A/Shanghai/2/2013 Strain of Influenza Disease Vaccine-heterologous (H7N9)
timeFrame: At Days 0, 21 and 42 and at Months 6 and 12
measure: Number of Seroprotected (SPR) Subjects Against HI Antibodies for Vaccine-heterologous (H7N9)
timeFrame: At Days 0, 21 and 42 and at Months 6 and 12
measure: Number of Seroconverted (SCR) Subjects for HI Antibodies for Vaccine-heterologous (H7N9)
timeFrame: At Days 21 and 42 and at Months 6 and 12
measure: Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/Shanghai/2/2013 Strain of Influenza Disease Vaccine-heterologous (H7N9)
timeFrame: At Days 21 and 42 and at Months 6 and 12
measure: Number of Subjects With HI Neutralizing Antibody Concentrations Above the Cut-off Value for Vaccine-homologous (H7N1)
timeFrame: At Days 0, 21 and 42 and Month 6
measure: Titers for Serum Neutralizing Antibodies Against Flu A/Mallard/NL/12/2000 Strain of Influenza Disease Vaccine-homologous (H7N1)
timeFrame: At Days 0, 21 and 42 and at Month 6
measure: Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Against the Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain
timeFrame: At Days 21 and 42 and at Month 6
measure: Number of Subjects With HI Neutralizing Antibody Concentrations Above the Cut-off Value for Vaccine-heterologous (H7N9)
timeFrame: At Days 0, 21 and 42 and at Month 6
measure: Titers for Antibodies Against Flu A/Anhui/1/2013 Strain of Influenza Disease Vaccine-homologous (H7N9)
timeFrame: At Days 0, 21 and 42 and at Month 6
measure: Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Against the Flu A/Anhui/1/2013 (H7N9) Virus Strain
timeFrame: At Days 21 and 42 and at Month 6
measure: Number of Subjects With Any Medically-attended Adverse Events (MAEs)
timeFrame: From Day 42 up to Month 12
measure: Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs)
timeFrame: From Day 42 up to Month 12
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: During the 21-day (From Day 0 to Day 20) post-vaccination period after each dose
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the entire study period (From Day 0 up to Month 12)
Other outcomes:
Locations:
city: Hollywood
country: United States
facility: GSK Investigational Site
state: Florida
city: Meridian
country: United States
facility: GSK Investigational Site
state: Idaho
city: Lenexa
country: United States
facility: GSK Investigational Site
state: Kansas
city: Wichita
country: United States
facility: GSK Investigational Site
state: Kansas
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Truro
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Sudbury
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Madan A, Ferguson M, Rheault P, Seiden D, Toma A, Friel D, Soni J, Li P, Innis BL, Schuind A. Immunogenicity and safety of an AS03-adjuvanted H7N1 vaccine in adults 65years of age and older: A phase II, observer-blind, randomized, controlled trial. Vaccine. 2017 Apr 4;35(15):1865-1872. doi: 10.1016/j.vaccine.2017.02.057. Epub 2017 Mar 13.