Immunogenicity and Safety Study of Different Formulations of GlaxoSmithKline (GSK) Biologicals H7N1 Influenza Vaccine Administered to Adults 65 Years of Age and Older

NCT01949090 | Completed Phase 2 Results

• 1 other identifier: 200613
• Study Type: interventional
• Target: 363
• Locations: 2 countries
• Sites: 8

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.

Conditions

Influenza

Keywords

H7N1; AS03 adjuvant; Safety; Immunogenicity; Influenza; Adults; Elderly adults

Outcome Measures

Primary Outcomes (14)

• Number of Seroconverted (SCR) Subjects for Hemagglutination Inhibition (HI) Antibodies Against the Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain

  Seroconversion was defined as: For initially seronegative subjects \[antibody titer below (\<) 10 post-vaccination\], antibody titer greater than or equal to (≥) 40 after vaccination; For initially seropositive subjects (antibody titer ≥ 10 prior to vaccination), antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. The Flu strain assessed was A/mallard/Netherlands/12/2000 NIBRG-63 (H7N1) (Flu A/mallard/NL/12/2000 H7N1).

  At Day 42

• Number of Subjects Who Were Seroprotected for HI Antibodies Against the Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain

  A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40, that usually is accepted as indicating protection.

  At Day 42

• Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain

  GMFR, also known as seroconversion factor (SCR) or mean geometric increase (MGI), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer for the vaccine virus.

  At Day 42

• Number of Subjects With Any and Grade 3 Solicited Local Symptoms

  Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest; prevented normal activities as assessed by inability to attend/do work or school. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.

  During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

• Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

  Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (symptoms included nausea, vomiting, diarrhoea and/or abdominal pain), headache, joint pain at other location, muscle aches, shivering, sweating and fever \[defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination. Grade 3 symptom = general symptom that prevented normal everyday activities as assessed by inability to attend/do work or school, or required intervention of a physician/healthcare provider. Grade 3 fever = temperature \> 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

  During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

• Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values

  Among analysed biochemical parameters were alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], basophils \[BAS\], creatinine \[CRE\], eosinophils \[EOS\], hematocrit \[HEM\], hemoglobin \[HgB\], lymphocytes \[LYM\], monocytes \[MON\], neutrophils \[NEU\], platelets \[PLA\], red blood cells \[RBC\] and white blood cells \[WBC\].

  At Day 0

• Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values

  Among analysed biochemical parameters were alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], basophils \[BAS\], creatinine \[CRE\], eosinophils \[EOS\], hematocrit \[HEM\], hemoglobin \[HgB\], lymphocytes \[LYM\], monocytes \[MON\], neutrophils \[NEU\], platelets \[PLA\], red blood cells \[RBC\] and white blood cells \[WBC\].

  At Day 7

• Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values

  Among analysed biochemical parameters were alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], basophils \[BAS\], creatinine \[CRE\], eosinophils \[EOS\], hematocrit \[HEM\], hemoglobin \[HgB\], lymphocytes \[LYM\], monocytes \[MON\], neutrophils \[NEU\], platelets \[PLA\], red blood cells \[RBC\] and white blood cells \[WBC\].

  At Day 21

• Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values

  Among analysed biochemical parameters were alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], basophils \[BAS\], creatinine \[CRE\], eosinophils \[EOS\], hematocrit \[HEM\], hemoglobin \[HgB\], lymphocytes \[LYM\], monocytes \[MON\], neutrophils \[NEU\], platelets \[PLA\], red blood cells \[RBC\] and white blood cells \[WBC\].

  At Day 28

• Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values

  Among analysed biochemical parameters were alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], basophils \[BAS\], creatinine \[CRE\], eosinophils \[EOS\], hematocrit \[HEM\], hemoglobin \[HgB\], lymphocytes \[LYM\], monocytes \[MON\], neutrophils \[NEU\], platelets \[PLA\], red blood cells \[RBC\] and white blood cells \[WBC\].

  At Day 42

• Number of Subjects With Any Medically-attended Adverse Events (MAEs)

  MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any MAE(s) = Occurrence of any MAE(s) regardless of intensity grade or relation to vaccination.

  From Day 0 up to Day 42

• Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs)

  Any pIMD was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration.

  From Day 0 up to Day 42

• Number of Subjects With Any Unsolicited Adverse Events (AEs)

  An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

  From Day 0 up to Day 42

• Number of Subjects With Serious Adverse Events (SAEs)

  SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  From Day 0 up to Day 42

Secondary Outcomes (20)

• Number of Subjects With HI Antibody Concentrations Above the Cut-off Value for Vaccine-homologous (H7N1)

  At Days 0, 21, 42 and Months 6 and 12

• Titers for Antibodies Against Flu A/Mallard/NL/12/2000 Strain of Influenza Disease Vaccine-homologous (H7N1)

  At Days 0, 21, 42 and Months 6 and 12

• Number of Seroprotected (SPR) Subjects Against HI Antibodies for Vaccine-homologous (H7N1)

  At Days 0, 21 and 42 and at Months 6 and 12

• Number of Seroconverted (SCR) Subjects for HI Antibodies for Vaccine-homologous (H7N1)

  At Days 21 and 42 and at Months 6 and 12

• Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/Mallard/NL/12/2000 Strain of Influenza Disease Vaccine-homologous (H7N1)

  At Days 21 and 42 and at Months 6 and 12

Study Arms (5)

GSK2789869A F1 Group

EXPERIMENTAL

Healthy male and female adults, 65 years of age and older, who received two doses of GSK2789869A H7N1 vaccine Formulation 1 (F1), administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and of the dominant arm at Day 21.

Biological: Investigational H7N1 vaccine GSK2789869A

GSK2789869A F2 Group

EXPERIMENTAL

Healthy male and female adults, 65 years of age and older, who received two doses of GSK2789869A H7N1 vaccine Formulation 2 (F2), administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and of the dominant arm at Day 21.

Biological: Investigational H7N1 vaccine GSK2789869A

GSK2789869A F3 Group

EXPERIMENTAL

Healthy male and female adults, 65 years of age and older, who received two doses of GSK2789869A H7N1 vaccine Formulation 3 (F3), administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and of the dominant arm at Day 21.

Biological: Investigational H7N1 vaccine GSK2789869A

GSK2789869A F4 Group

EXPERIMENTAL

Healthy male and female adults, 65 years of age and older, who received two doses of GSK2789869A H7N1 vaccine Formulation 4 (F4), administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and of the dominant arm at Day 21.

Biological: Investigational H7N1 vaccine GSK2789869A

Placebo Group

PLACEBO COMPARATOR

Healthy male and female adults, 65 years of age and older, who received two doses of Placebo, administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and of the dominant arm at Day 21.

Biological: Placebo

Interventions

Investigational H7N1 vaccine GSK2789869A BIOLOGICAL

Two doses of GSK2789869A H7N1 vaccine administered intramuscularly to the deltoid region at Day 0 and Day 21.

GSK2789869A F1 Group; GSK2789869A F2 Group; GSK2789869A F3 Group; GSK2789869A F4 Group

Placebo BIOLOGICAL

Two doses of placebo administered intramuscularly to the deltoid region at Day 0 and Day 21.

Placebo Group

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (8)

GSK Investigational Site

Hollywood, Florida, 33024, United States

Location

GSK Investigational Site

Meridian, Idaho, 83642, United States

Location

GSK Investigational Site

Lenexa, Kansas, 66219, United States

Location

GSK Investigational Site

Wichita, Kansas, 67207, United States

Location

GSK Investigational Site

Lexington, Kentucky, 40509, United States

Location

GSK Investigational Site

Truro, Nova Scotia, B2N 1L2, Canada

Location

GSK Investigational Site

Greater Sudbury, Ontario, P3E 1H5, Canada

Location

GSK Investigational Site

Toronto, Ontario, M9W 4L6, Canada

Location

Related Publications (1)

• 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.

  PMID: 28302407 DERIVED

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2013
• First Posted: September 24, 2013
• Study Start: September 25, 2013
• Primary Completion: December 4, 2013
• Study Completion: October 23, 2014
• Last Updated: November 17, 2017
• Results First Posted: November 17, 2017

Record last verified: 2017-11

Locations

CA (3); US (5)