A Study for Evaluation of GSK Biologicals' Pandemic Influenza Vaccine.

Non-inferiority Study of GSK Biologicals' Pandemic Influenza Vaccine 1562902A.

This observer-blind study is designed to show the immunological non-inferiority of Thiomersal-free-processed pandemic influenza vaccine as compared to the Thiomersal-containing-processed pandemic influenza vaccine.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: GSK1562902A; Biological: GSK1562902A

• Study Type: Interventional
• Enrollment (Actual): 320
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
• A male or female aged 18 to 60 years at the time of the first vaccination.
• Written informed consent obtained from the subject.
• Good general health as established by medical history and clinical examination before entering into the study.
• 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
• Comprehension of the study requirements, ability to comprehend and comply with procedures for collection of short- and long-term safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits.
• If the subject is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series.

Exclusion Criteria:

• Evidence of substance abuse or of neurological or psychiatric diagnoses which, even if clinically stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.
• Diagnosed with cancer, or treatment for cancer, within 3 years.
• An oral temperature ≥ 37.8 º 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 systemic glucocorticoids (prednisone ≥ 5 mg/kg/day for more than 14 consecutive days) within 1 month of study enrolment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrolment.
• Any significant disorder of coagulation or treatment with Coumarin derivatives or Heparin.
• Administration of any vaccines within 30 days before study enrolment.
• Previous administration of any H5N1 vaccine.
• Previous administration of vaccines with adjuvants similar to those used in the investigational vaccine.
• Use of any investigational or non-registered product (drug or vaccine) or planned participation in another investigational study within 30 days prior to study enrolment, or during the 180 days following the first test article dose. Use of any investigational or non-registered product with immunosuppressive properties is exclusionary at any time during the trial.
• Receipt of any immunoglobulins and/or any blood products within 3 months of study enrolment or planned administration of any of these products during the study period.
• Any known or suspected allergy to any constituent of influenza vaccines (including egg proteins or mercurial preservatives); 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 prior to either vaccination.
• Lactating women.
• Women of child bearing potential who lack a history of reliable contraceptive practices. The provision of this history does NOT replace the requirement to perform, and obtain negative results in pregnancy urine tests prior to treatments.
• Known use of an analgesic or antipyretic medication within 12 hours prior to first treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1562902A NP GROUP; Healthy male or female adults, between and including 18 to 60 years of age, who received two doses of the new-processed (NP) 1562902A vaccine, administered intramuscularly in the deltoid region of the non-dominant arm, at Days 0 and 21.	Biological: GSK1562902A; new-processed (NP), administered intramuscularly in the deltoid region of the non-dominant arm; Biological: GSK1562902A; comparative-processed (CP), administered intramuscularly in the deltoid region of the non-dominant arm
Experimental: 1562902A CP GROUP; Healthy male or female adults, between and including 18 to 60 years of age, who received two doses of the comparative-processed (CP) 1562902A vaccine, administered intramuscularly in the deltoid region of the non-dominant arm, at Days 0 and 21.	Biological: GSK1562902A; new-processed (NP), administered intramuscularly in the deltoid region of the non-dominant arm; Biological: GSK1562902A; comparative-processed (CP), administered intramuscularly in the deltoid region of the non-dominant arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titers for Serum H5N1 Haemagglutination-inhibition (HI) Antibodies	Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strain assessed was A/Indonesia/05/2005.	At Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 = pain that prevented normal activity. 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
Titers for Serum H5N1 HI Antibodies	Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.	At Day 0 and Day 180
Number of Subjects With H5N1 HI Antibody Concentrations Above the Cut-off Value	The cut-off values for the humoral immune response in terms of H5N1 HI antibodies were equal to or above (≥) 1:10. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.	At Days 0, 42 and 180
Number of Seroconverted Subjects Against Two Strains of Influenza Disease	A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer below (<) 1:10 and a post-vaccination titer equal to or above (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination titer. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.	At Day 42 and Day 180
Seroconversion Factor (SCF) for H5N1 HI Antibodies	The seroconversion factor (SCF) was defined as the fold increase in H5N1 HI antibody GMTs post-vaccination compared to Day 0. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.	At Day 42 and Day 180
Number of Seroprotected Subjects for H5N1 HI Antibodies	A seroprotected subject was defined as a vaccinated subject with a serum HI titer equal to or above (≥) 1:40. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.	At Days 0, 42 and 180
Titers for Serum Neutralising Antibodies Against A/Vietnam/1194/2004 Strain of Influenza Disease	Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:28. The flu strain assessed was A/Vietnam/1194/2004.	At Days 0, 42 and 180
Number of Subjects With Neutralizing Antibody Concentrations Above the Cut-off Value	Seropositivity cut-off values assessed were equal to or above (≥) 1:28 in the sera of subjects seronegative before vaccination. The flu strain assessed was A/Vietnam/1194/2004.	At Days 0, 42 and 180
Number of Seroconverted Subjects for Neutralizing Antibodies	A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer < 1:28 and a post-vaccination titer ≥ 1:56 or a pre-vaccination titer ≥ 1:28 and at least a four-fold increase in post-vaccination titer. The flu strain assessed was A/Vietnam/1194/2004.	At Day 42 and Day 180
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were arthralgia, fatigue, headache, myalgia, 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. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination.	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Any Adverse Events of Specific Interest (AESIs)	An AESI 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 51 days after the first vaccination
Number of Subjects With Any AESIs	An AESI was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration.	During the entire study period (from Day 0 up to Day 180)
Number of Subjects With Any, Grade 3 and Related 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. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.	During the 21-day follow-up period after the first vaccination and 30-day follow-up period after the second vaccination
Number of Subjects With Any, Grade 3 and Related 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. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.	During the entire study period (from Day 0 up to Day 180)
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 51
Number of Subjects With SAEs	SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	During the entire study period (from Day 0 up to Day 180)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Yang PC, Yu CJ, Chang SC, Hsieh SM, Drame M, Walravens K, Roman F, Gillard P. Safety and immunogenicity of a split-virion AS03A-adjuvanted A/Indonesia/05/2005 (H5N1) vaccine in Taiwanese adults. J Formos Med Assoc. 2012 Jun;111(6):333-9. doi: 10.1016/j.jfma.2011.02.006. Epub 2012 Apr 20.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2008
• Primary Completion (Actual): June 7, 2009
• Study Completion (Actual): June 7, 2009

Study Registration Dates

• First Submitted: December 18, 2008
• First Submitted That Met QC Criteria: December 18, 2008
• First Posted (Estimate): December 22, 2008

Study Record Updates

• Last Update Posted (Actual): August 20, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Pandemic influenza
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: 111954

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. Study Protocol
   Information identifier: 111954
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 111954
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 111954
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 111954
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 111954
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 111954
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Annotated Case Report Form
   Information identifier: 111954
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register