Study to Evaluate the Safety and Immune Response of Two-Doses of Candidate Influenza Vaccine GSK 1557484A in Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00510874
First received: August 1, 2007
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to evaluate the safety and immune response of two-doses of GSK Biologicals' candidate influenza vaccine GSK 1557484A with or without adjuvant in adults. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.


Condition Intervention Phase
Influenza
Biological: Pumarix™
Biological: Pandemrix ™
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Phase I/II, Observer-Blind, Randomized, Active-Controlled Trial to Evaluate the Safety and Immunogenicity of a Two-Dose Series of GSK Biologicals' Candidate Influenza Vaccine GSK 1557484A Antigens With or Without Adjuvant

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Seroconverted Subjects Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer less than (<) 1:10 and a post-vaccination reciprocal titer greater than or equal to (≥) 1:40 or a pre-vaccination reciprocal titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer on the specified day.

  • Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs).

  • Number of Seroprotected Subjects Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:40.

  • Number of Subjects With Solicited Local Symptoms. [ Time Frame: Within the 7-day follow-up period (Days 0-6) after any vaccination ] [ Designated as safety issue: No ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any solicited local symptoms regardless of their intensity grade. Any redness and swelling were ≥ 20 millimeters (mm).

  • Number of Subjects With Solicited General Symptoms. [ Time Frame: Within the 7-day follow-up period (Days 0-6) after any vaccination ] [ Designated as safety issue: No ]
    Assessed solicited general symptoms were fatigue, headache, joint pain at other location (joint pain), muscle aches, shivering, sweating and fever. Fever was defined as oral temperature (≥) 38 degrees Celsius (°C). Any = occurrence of any solicited general symptoms regardless of intensity grade or relationship to vaccination.

  • Number of Subjects With Medically Attended Adverse Events (MAEs) and New Onset Chronic Diseases (NOCDs). [ Time Frame: From Day 0 to 182 ] [ Designated as safety issue: No ]
    A MAE was defined as any unsolicited symptom that received medical attention such as hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. NOCDs included autoimmune diseases, diabetes mellitus.

  • Number of Subjects With Unsolicited Adverse Events (AEs). [ Time Frame: During the 21-day follow-up period (Days 0-20) after vaccination. ] [ Designated as safety issue: No ]
    An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with 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.

  • Number of Subjects With Unsolicited Adverse Events (AEs). [ Time Frame: Between Day 0 and Day 84 after vaccination. ] [ Designated as safety issue: No ]
    An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with 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.

  • Number of Subjects With Any Serious Adverse Events (SAEs). [ Time Frame: From Day 0 to 182 ] [ Designated as safety issue: No ]
    A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or resulted in a congenital anomaly/birth defect in the offspring of a study subject.


Secondary Outcome Measures:
  • Titers for Serum HI Antibodies Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. [ Time Frame: At Day 21 and Day 182 ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs).

  • Number of Seroconverted Subjects Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. [ Time Frame: At Days 21 and 182 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer less than (<) 1:10 and a post-vaccination reciprocal titer greater than or equal to (≥) 1:40 or a pre-vaccination reciprocal titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer on the specified day.

  • Geometric Mean Fold-rise (GMFR) Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. [ Time Frame: At Days 21 and 182 ] [ Designated as safety issue: No ]
    GMFR was defined as the geometric mean fold increase in serum HI antibody reciprocal titer on the specified study day compared to Day 0.

  • Number of Seroprotected Subjects Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. [ Time Frame: At Days 0, 21 and 182 ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had a serum HI antibody reciprocal titer ≥ 1:40 on the specified study day.


Enrollment: 780
Study Start Date: July 2007
Study Completion Date: October 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pumarix Formulation 1 Group
Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of formulation 1 of Pumarix™ vaccine at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm (non-dominant arm for the first injection and dominant arm for the second one).
Biological: Pumarix™
Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.
Experimental: Pumarix Formulation 2 Group
Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of formulation 2 of Pumarix™ vaccine at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm (non-dominant arm for the first injection and dominant arm for the second one).
Biological: Pumarix™
Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.
Experimental: Pumarix Formulation 3 Group
Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of formulation 3 of Pumarix™ vaccine at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm (non-dominant arm for the first injection and dominant arm for the second one).
Biological: Pumarix™
Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.
Experimental: Pandemrix Formulation A Group
Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of formulation A of Pandemrix™ vaccine at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm (non-dominant arm for the first injection and dominant arm for the second one).
Biological: Pandemrix ™
Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.
Experimental: Pandemrix Formulation B Group
Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of formulation B of Pandemrix ™ vaccine at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm (non-dominant arm for the first injection and dominant arm for the second one).
Biological: Pandemrix ™
Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.
Experimental: Pumarix Formulation 4 Group
Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of formulation 4 of Pumarix™ vaccine at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm (non-dominant arm for the first injection and dominant arm for the second one).
Biological: Pumarix™
Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.
Experimental: Pumarix Formulation 5 Group
Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of formulation 5 of Pumarix™ vaccine at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm (non-dominant arm for the first injection and dominant arm for the second one).
Biological: Pumarix™
Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.

Detailed Description:

The study has five core arms and the stratification is based on site and age. In addition, there are 4 possible contingent groups of which 2 will be studied based on an analysis concerning immunogenicity performance at Day 42 in core groups above.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male and female adults 18 to 64 years of age at time of first vaccination, inclusive.
  • Good general health as assessed by medical history and physical examination.
  • Access to a consistent means of telephone contact
  • Written informed consent obtained from the subject.
  • Comprehension of the study requirements, expressed availability for the required study period, and ability to attend scheduled visits.
  • Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.

Exclusion Criteria:

  • Presence of significant acute or chronic, uncontrolled medical or psychiatric illness
  • 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.
  • Blood pressure abnormalities
  • 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 histologically-confirmed basal cell carcinoma of the skin successfully treated with local excision only are excepted and may enroll, but other histologic types of skin cancer are exclusionary.
  • Women who are disease-free 3 years or more after treatment for breast cancer and receiving long-term prophylactic tamoxifen are excepted and may enroll.
  • Presence of an oral temperature ≥ 37.8º C, 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 cytotoxic or immunosuppressive drug within 6 months of study enrollment.
  • Any significant disorder of coagulation or treatment with Coumadin derivatives or heparin.
  • Administration of any non-influenza vaccines within 30 days before study enrollment or during the study period.
  • Use of any investigational or non-registered product (drug or vaccine) or planned participation in another investigational study within 30 days prior to study enrollment, or during the study period.
  • Receipt of any immunoglobulins and/or any blood products within 3 months of study enrollment or planned administration of any of these products during the study period.
  • Any known or suspected allergy to any constituent of influenza vaccines.
  • Known pregnancy or a positive urine beta-human chorionic gonadotropin (ß-hCG) test result prior to dosing on Study Days 0 or 21.
  • Lactating or nursing.
  • Women of child bearing potential who lack a history of reliable contraceptive practices.
  • Known receipt of analgesic or antipyretic medication on the day of treatment
  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: NCT00510874

Locations
United States, Alabama
GSK Investigational Site
Huntsville, Alabama, United States, 35802
United States, California
GSK Investigational Site
Anaheim, California, United States, 92801
United States, Florida
GSK Investigational Site
Miami, Florida, United States, 33143
United States, Georgia
GSK Investigational Site
Stockbridge, Georgia, United States, 30281
United States, Kansas
GSK Investigational Site
Lenexa, Kansas, United States, 66219
United States, Montana
GSK Investigational Site
Missoula, Montana, United States, 59801
United States, Nevada
GSK Investigational Site
Las Vegas, Nevada, United States, 89104
Canada, Nova Scotia
GSK Investigational Site
Halifax, Nova Scotia, Canada, B3K 6R8
GSK Investigational Site
Truro, Nova Scotia, Canada, B2N 1L2
Canada, Quebec
GSK Investigational Site
Sherbrooke, Quebec, Canada, J1H 4J6
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Langley J et al. Safety and cross-reactive immunogenicity of two H5N1 A/Indonesia/5/2005 (clade 2.1) AS03-adjuvanted prepandemic candidate influenza vaccines. A phase I/II clinical trial. Abstract presented at the Third European Influenza Conference, Vilamoura, Portugal, 14-17 September 2008.
Langley J et al. Safety and Cross-Reactive Immunogenicity of Two H5N1A/Indonesia/5/2005 (Clade 2.1) AS-Adjuvanted Prepandemic Candidate Influenza Vaccines: A Phase I/II Clinical Trial. Abstract presented at the 13th International Congress on Infectious Diseases (ICID), Kuala Lumpur, Malaysia, 19-22 June 2008.
Langley J et al. Safety and cross-reactive immunogencity of two H5N1 A/Indoesia/5/2005 (clade 2.1 AS03-adjuvanted prepandemic candidate influenza vaccines. A phase I/II clinical trial. Abstract presented at the Canadian Pandemic Preparedness Meeting: From Discovery to Frontlines held by the Canadian Institutes of Health Research, Winnipeg, Canada, 6-8 November 2008.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00510874     History of Changes
Other Study ID Numbers: 110028
Study First Received: August 1, 2007
Results First Received: December 19, 2013
Last Updated: December 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Influenza
GSK 1557484A vaccine

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

ClinicalTrials.gov processed this record on October 23, 2014