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Evaluation of the Immune Response and the Safety of a Pandemic Influenza Candidate Vaccine (H1N1)

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00971425
First received: August 27, 2009
Last updated: March 15, 2011
Last verified: February 2011
  Purpose

The objective of the study is to evaluate the immunogenicity and safety of GSK Biologicals' investigational vaccine GSK2340272A.


Condition Intervention Phase
Influenza A Virus, H1N1 Subtype
Influenza Infection
Biological: Pandemrix (GSK investigational influenza GSK2340272A vaccine)
Biological: Fluarix™
Biological: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: Immunogenicity and Safety of GSK Biologicals' Pandemic Influenza Candidate Vaccine GSK2340272A

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Geometric Mean Titers (GMTs) of Antibodies Against Pandemrix Vaccine Strain [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]

    Titers were expressed as GMTs.

    The Pandemrix vaccine strain was A/Cal/7/09.


  • Number of Subjects With a Titer Greater Than or Equal to 1:10 for Antibodies Against Pandemrix Vaccine Strain [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]

    The Pandemrix vaccine strain was A/Cal/7/09.

    The cut-off was a titer of 1:10 and this titer was considered as seropositivity.


  • Number of Seroconverted Subjects for Antibodies Against Pandemrix Vaccine Strain [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]

    The Pandemrix vaccine strain was A/Cal/7/09.

    A subject seroconverted for haemagglutination inhibition (HI) antibodies was defined as a subject with either a prevaccination (Day 0) HI antibody titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a prevaccination titer greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titer.


  • Seroconversion Factor for Antibodies Against Pandemrix Vaccine Strain [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]

    Seroconversion Factor (SCF) is defined as the fold increase in serum HI antibody GMTs post-vaccination compared to prevaccination (Day 0).

    The Pandemrix vaccine strain was A/Cal/7/09.


  • Number of Seroprotected Subjects for Antibodies Against Pandemrix Vaccine Strain [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]

    The Pandemrix vaccine strain was A/Cal/7/09.

    A seroprotected subject was defined as a subject with a serum HI antibody titer greater than or equal to 1:40.



Secondary Outcome Measures:
  • Geometric Mean Titers (GMTs) of Antibodies Against Pandemrix Vaccine Strain and Fluarix Vaccine Strains [ Time Frame: Day -21, Day 0, Day 21, Day 42, Day 63, Month 6 and Month 12 ] [ Designated as safety issue: No ]

    Pandemrix vaccine strain (A/Cal/7/09) data were assessed up to Month 12. Note that Day 42 data for Pandemrix vaccine strain were already addressed as a primary outcome measure.

    Fluarix vaccine strains (A/Bri/59/07, B/Bri/60/08, and A/Uru/716/07) data were only assessed up to Day 63.


  • Number of Subjects With a Titer Greater Than or Equal to 1:10 for Antibodies Against Pandemrix Vaccine Strain and Fluarix Vaccine Strains [ Time Frame: At Day -21, Day 0, Day 21, Day 42, Day 63, Month 6 and Month 12 ] [ Designated as safety issue: No ]

    The cut-off was a titer of 1:10 and this titer was considered as seropositivity.

    Pandemrix vaccine strain (A/Cal/7/09) data were assessed up to Month 12. Note that Day 42 data for Pandemrix vaccine strain were already addressed as a primary outcome measure.

    Fluarix vaccine strains (A/Bri/59/07, B/Bri/60/08, and A/Uru/716/07) data were only assessed up to Day 63.


  • Number of Seroconverted Subjects for Antibodies Against Pandemrix Vaccine Strain and Fluarix Vaccine Strains [ Time Frame: At Day 21, Month 6 and Month 12 for Pandemrix vaccine strain, and at Day 0/Day 63 for Fluarix vaccine strains. ] [ Designated as safety issue: No ]

    A seroconverted subject was defined as a subject with either a prevaccination (Day 0) HI antibody titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a prevaccination titer greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titer.

    Pandemrix vaccine strain (A/Cal/7/09) data were generated for Day 21, Month 6 and Month 12.

    Fluarix vaccine strains (A/Bri/59/07, B/Bri/60/08, and A/Uru/716/07) data were generated at 21 days after Fluarix administration, i.e. depending on the group at Day 0 or Day 63 (Day 0/Day 63).


  • Seroconversion Factor for Antibodies Against Pandemrix Vaccine Strain and Fluarix Vaccine Strains [ Time Frame: At Day 21, Month 6 and Month 12 for Pandemrix vaccine strain, and at Day 0/Day 63 for Fluarix vaccine strains. ] [ Designated as safety issue: No ]

    For the definition of seroconversion factor, please refer to the primary outcome measure.

    Pandemrix vaccine strain (A/Cal/7/09) data were generated for Day 21, Month 6 and Month 12.

    Fluarix vaccine strains (A/Bri/59/07, B/Bri/60/08, and A/Uru/716/07) data were generated at 21 days after Fluarix administration, i.e. depending on the group at Day 0 or Day 63 (Day 0/Day 63).


  • Number of Seroprotected Subjects for Antibodies Against Pandemrix Vaccine Strain and Fluarix Vaccine Strains [ Time Frame: Day -21, Day 0, Day 21, Day 42, Day 63, Month 6 and Month 12 ] [ Designated as safety issue: No ]

    A seroprotected subject was defined as a subject with a serum HI antibody titer greater than or equal to 1:40.

    Pandemrix vaccine strain (A/Cal/7/09) data were assessed up to Month 12. Note that Day 42 data for Pandemrix vaccine strain were already addressed as a primary outcome measure.

    Fluarix vaccine strains (A/Bri/59/07, B/Bri/60/08, and A/Uru/716/07) data were only assessed up to Day 63.


  • Number of Subjects With Solicited Local and General Symptoms After Administration of Pandemrix [ Time Frame: During a 7-Day (Day 0-6) follow-up period after each administration of Pandemrix ] [ Designated as safety issue: No ]
    Solicited local symptoms were pain, redness and swelling at the injection site. Solicited general symptoms were fatigue, headache, joint pain at other location, muscle aches, shivering, sweating, temperature (defined as axillary temperature equal to or above 37.5 degrees Celsius).

  • Number of Subjects With Solicited Local and General Symptoms After Administration of Placebo or Fluarix [ Time Frame: During a 7-Day (Day 0-6) follow-up period after each administration of (at Day -21 and at Day 42) placebo or Fluarix ] [ Designated as safety issue: No ]
    Solicited local symptoms were pain, redness and swelling at the injection site. General symptoms were fatigue, headache, joint pain at other location, muscle aches, shivering, sweating, temperature (defined as axillary temperature equal to or above 37.5 degrees Celsius)

  • Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [ Time Frame: During 21 days (Day 0-20) after each vaccination ] [ Designated as safety issue: No ]

    Unsolicited AE covers any AE 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: any unsolicited AE regardless of intensity or relationship to vaccination. Grade 3: unsolicited AE that prevented normal everyday activity Related: unsolicited AE assessed by the investigator as related to the vaccination


  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: During the entire study period (Day 0-364) ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

  • Number of Subjects With AEs of Specific Interest [ Time Frame: During the entire study period (Day 0-364) ] [ Designated as safety issue: No ]
    Adverse events of specific interest included auto-immune diseases and other immune mediated disorders.


Enrollment: 145
Study Start Date: September 2009
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Placebo-Pandemrix-Fluarix Group
Subjects received one dose of placebo intramuscularly in the deltoid region of the dominant arm at Day -21, 2 doses of Pandemrix (GSK2340272A) intramuscularly in the deltoid region of the non-dominant arm at Day 0 and Day 21, and 1 dose of Fluarix intramuscularly in the deltoid region of the dominant arm at Day 42.
Biological: Pandemrix (GSK investigational influenza GSK2340272A vaccine)
2 doses intramuscular injections
Biological: Fluarix™
1 dose intramuscular injection
Biological: Placebo
1 dose intramuscular injection
Experimental: Fluarix-Pandemrix-Placebo Group
Subjects received 1 dose of Fluarix intramuscularly in the deltoid region of the dominant arm at Day -21, 2 doses of Pandemrix (GSK2340272A) intramuscularly in the deltoid of the non-dominant arm at Day 0 and 21, and 1 dose of placebo intramuscularly in the deltoid of the non-dominant arm at Day 42.
Biological: Pandemrix (GSK investigational influenza GSK2340272A vaccine)
2 doses intramuscular injections
Biological: Fluarix™
1 dose intramuscular injection
Biological: Placebo
1 dose intramuscular injection

  Eligibility

Ages Eligible for Study:   61 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or female subjects 61 years of age or older at the time of the first vaccination.
  • Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
  • Written informed consent obtained from the subject.
  • Satisfactory baseline medical assessment by history and physical examination (stable health status with no exclusionary medical or psychiatric conditions). Stable health status is defined as the absence of 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 one month prior to enrolment.

Exclusion Criteria:

  • Previous administration of the 2009 Southern Hemisphere or 2009-2010 Northern Hemisphere influenza vaccine.
  • Previous administration of a pandemic influenza vaccine.
  • Administration of any vaccine within 30 days before first vaccination.
  • Planned administration of a vaccine not foreseen by the study protocol one month (minimum 30 days) after the second vaccination with the GSK2340272A candidate vaccine.
  • Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of the study vaccines or planned use during the study period. Potential subjects in the follow-up phase of a prior investigational study may be enrolled if the investigator's judgment is that it will have no effect on safety, reactogenicity, or immunogenicity endpoints in this study, and that it does not violate the protocol requirements of the prior trial.
  • Presence of evidence of substance abuse or 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 of an axillary temperature >= 37.5°C, 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, vaccination occurs within the window specified by the protocol, and all other eligibility criteria continue to be satisfied.
  • Diagnosed with cancer, or treatment for cancer, within 3 years.

    • Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible.
    • Persons with a history of histological-confirmed basal cell carcinoma of the skin successfully treated with local excisions only are eligible and may be enrolled within 3 years of diagnosis, but other histological types of skin cancer require a 3-year untreated and disease-free window as above.
    • Women who are disease free for 3 years or more after the treatment of breast cancer and receiving long-term prophylactic tamoxifen are eligible and may be enrolled.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection.
  • Chronic administration of immunosuppressants or other immune modifying drugs within six months prior to the first vaccination and during the entire study period.
  • Receipt of any immunoglobulins and/or any blood products within 3 months preceding the first vaccination or planned administration of any of these products during the entire study period.
  • 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 history of Guillain-Barré syndrome.
  • Serious chronic disease including any medically significant chronic pulmonary, cardiovascular, renal, neurological, psychiatric or metabolic disorder, as determined by medical history and physical examination. (Subjects suffering from seasonal allergies or asthma under inhalative treatment can be included, as well as subjects with well controlled underlying diseases).
  • Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormalities, as determined by physical examination or laboratory screening tests.
  • Any known or suspected allergy to any constituent of influenza vaccines; a history of anaphylactic-type reaction to any constituent of influenza vaccines; or a history of severe adverse reaction to a previous influenza vaccine.
  • History of chronic alcohol consumption and/or drug abuse.
  • Clinically or virologically confirmed influenza infection within 6 months preceding the study start.
  • Any conditions which, in the opinion of the investigator, prevents the subjects from participating in the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00971425

Locations
Germany
GSK Investigational Site
Rednitzhembach, Bayern, Germany, 91126
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55116
GSK Investigational Site
Freital, Sachsen, Germany, 01705
GSK Investigational Site
Berlin, Germany, 12157
GSK Investigational Site
Hamburg, Germany, 22415
GSK Investigational Site
Hamburg, Germany, 22335
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00971425     History of Changes
Other Study ID Numbers: 113572
Study First Received: August 27, 2009
Results First Received: February 10, 2011
Last Updated: March 15, 2011
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by GlaxoSmithKline:
influenza infection
GSK Bio's influenza vaccine GSK2340272A

Additional relevant MeSH terms:
Infection
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Respiratory Tract Diseases
Respiratory Tract Infections
Virus Diseases

ClinicalTrials.gov processed this record on November 27, 2014