Clinical trial NCT00719043: Immunogenicity & Safety of GSK's Avian Flu Vaccine 1557484A Given to Adults Aged ≥18 Years
Official title: A Trial to Evaluate the Safety and Immunogenicity of Monovalent H5N1 Vaccine in Adults >=18 Yrs of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Keywords: Influenza
H5N1
Avian
Vaccines
Safety
Immunogenicity
Pandemic
Human
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-07-21
Enrollment: 841
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether GSK's avian flu vaccine GSK 1557484A is immunogenic and safe when given to adults aged \>=18 years.

This Protocol Posting has been updated following Amendments 1-3 of the Protocol, Dec 2009. The impacted sections are study design and outcome measures.

Detailed description: All subjects will receive 3 doses of study vaccine, including 2 doses of active vaccine and 1 dose of placebo. All subjects will attend formal study center visits for safety and immunogenicity assessments on Days 0, 10, 42, 182, 192, 224, 549, 559, 591, and 729. A telephone contact to assess safety will be made at Day 364 and Day 909.

Eligibility criteria: Inclusion Criteria:

* A male or female 18 years of age or older at the time of the first vaccination.
* Written informed consent obtained from the subject.
* Stable health status as 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.
* Comprehension of the study requirements, expressed availability for the required study period, and ability to attend scheduled visits.
* Subjects who the investigator believes can and will comply with the requirements of the protocol

Exclusion Criteria:

* Presence of 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.

  * 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 within 3 years of diagnosis, but other histologic types of skin cancer require a 3 year untreated and disease-free window as above.
  * 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 ≥ 37.8ºC, 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 \>= 10 mg/day for more than 14 consecutive days) within 1 month prior to study enrollment, or any other 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 vaccines within 30 days before the first study vaccine dose.
* Previous administration of any H5N1 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 enrollment, or during the 18 months 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 6 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 (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 vaccination.
* Lactating or nursing.
* 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 receipt of analgesic or antipyretic medication with the specific intent of prophylaxis of vaccine reactogenicity on the day of first or any treatment. Subjects on stable chronic regimens of potentially analgesic or anti-pyretic medications for pre-existing diagnoses are not required to discontinue them (to do so would represent evaluation of combined vaccine reactogenicity AND treatment withdrawal - which is not the intent of the protocol).

Primary outcomes:
measure: Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.
timeFrame: At Day 559
measure: Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.
timeFrame: At Day 192
measure: Haemagglutination Inhibition (HI) Antibody Titers Against the A/Turkey/Turkey/1/2005 (A/Turkey) Strain.
timeFrame: At Days 549 and 559
measure: Haemagglutination Inhibition (HI) Antibody Titers Against the A/Turkey/Turkey/1/2005 (A/Turkey) Strain.
timeFrame: At Days 182 and 192
measure: Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.
timeFrame: At Days 549 and 559
measure: Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.
timeFrame: At Days 182 and 192
measure: Number of Subjects With Solicited Local Symptoms
timeFrame: Within the 7-day (Days 0-6) post vaccination periods
measure: Number of Subjects With Solicited General Symptoms
timeFrame: Within the 7-day (Days 0-6) post vaccination periods
measure: Number of Subjects With Medically-attended Adverse Events (MAEs)
timeFrame: From Day 0 to Day 909
measure: Number of Subjects With Unsolicited Adverse Events (AEs)
timeFrame: Within the 43-day (Days 0-42) post-vaccination periods
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Day 0 to Day 909
Secondary outcomes:
measure: Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.
timeFrame: At Day 192
measure: Haemagglutination Inhibition (HI) Antibody Titers Against the A/Turkey Virus Strain.
timeFrame: At Days 182 and 192
measure: Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.
timeFrame: At Days 182 and 192
measure: Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.
timeFrame: At Day 224
measure: Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.
timeFrame: At Day 591
measure: Geometric Mean Fold Rise (GMFR) as Regards Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain
timeFrame: At Days 192 and 224
measure: Geometric Mean Fold Rise (GMFR) as Regards Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain
timeFrame: At Day 559
measure: Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.
timeFrame: At Day 591
measure: Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.
timeFrame: At Day 224
measure: Haemagglutination Inhibition (HI) Antibody Titers Against the A/Turkey/Turkey/1/2005 (A/Turkey) Strain.
timeFrame: At Days 0, 182,192, 224, 549 and 729
measure: Haemagglutination Inhibition (HI) Antibody Titers Against the A/Turkey/Turkey/1/2005 (A/Turkey) Strain.
timeFrame: At Days 0, 182, 549, 559, 591 and 729
measure: Haemagglutination Inhibition (HI) Antibody Titers Against the A/Turkey/Turkey/1/2005 (A/Turkey) Strain.
timeFrame: At Days 0, 182, 192, 224, 549, 559, 591 and 729
measure: Number of Subjects Seroprotected for HI Antibodies Against the A/Turkey/Turkey/1/2005 Virus Strain.
timeFrame: At Days 0, 182,192, 224, 549 and 729
measure: Number of Subjects Seroprotected for HI Antibodies Against the A/Turkey/Turkey/1/2005 Virus Strain
timeFrame: At Days 0, 182, 549, 559, 591 and 729
measure: Number of Subjects Seroprotected for HI Antibodies Against the A/Turkey/Turkey/1/2005 Virus Strain
timeFrame: At Days 0, 182, 192, 224, 549, 559, 591 and 729
measure: Haemagglutination Inhibition (HI) Antibody Titers Against the A/Indonesia/5/05 (A/Indo) Virus Strain.
timeFrame: At Days 0, 10, 42, 182 and 549
measure: Haemagglutination Inhibition (HI) Antibody Titers Against the A/Indonesia/5/05 (A/Indo) Virus Strain.
timeFrame: At Days 0, 10, 42, 182, 549 and 559
measure: Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against A/Indonesia/5/05 (A/Indo) Virus Strain.
timeFrame: At Day 0, Day 10, Day 42, Day 182 and Day 549
measure: Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against A/Indonesia/5/05 (A/Indo) Virus Strain.
timeFrame: At Day 0, Day 10, Day 42, Day 182, Day 549, and Day 559
measure: Number of Seroconverted Subjects for HI Antibodies Against the A/Indo Virus Strain.
timeFrame: At Days 10 and 42
measure: Number of Seroconverted Subjects for HI Antibodies Against the A/Indo Virus Strain.
timeFrame: At Days 192 and 224
Other outcomes:
Locations:
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Metairie
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Milford
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Missoula
country: United States
facility: GSK Investigational Site
state: Montana
city: Winston-Salem
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Bristol
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Halifax
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: