Clinical trial NCT00985088: Safety and Immunogenicity of H1N1 Vaccines in Adults Aged 18 Years and Older
Official title: A Study to Evaluate the Safety and Immunogenicity of A/California/7/2009 (H1N1)V-like Vaccines GSK2340273A and GSK2340274A in Adults Aged 18 Years and Older
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Keywords: GSK Bio's influenza vaccine GSK2340274A
influenza infection
GSK Bio's influenza vaccine GSK2340273A
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-09-28
Enrollment: 1343
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 characterize the safety and immunogenicity of the H1N1 (swine) flu vaccines GSK2340273A and GSK2340274A in adults 18 years of age or older.

This protocol posting has been updated for sections impacted by the Protocol amendment 1, Sept 2009.

Detailed description: Collaborators: United States Department of Health and Human Services, Office of Biomedical Advanced Research and Development Authority

Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes can and will comply with the requirements of the protocol.
* Written informed consent obtained from the subject.
* Male and female adults, \>= 18 years of age at the time of the first vaccination.
* Safety laboratory test results within the parameters specified in the protocol.
* Satisfactory baseline medical assessment by history and physical examination.
* Comprehension of the study requirements, ability to comprehend and comply with procedures for collection of safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits as documented by signature on the informed consent document.
* 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.
* Female subjects of non-childbearing potential may be enrolled in the study.
* Female subjects of childbearing potential may be enrolled in the study, if the subject:
* has practiced adequate contraception for 30 days prior to vaccination, and
* has a negative pregnancy test on the day of first vaccination, and
* has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

* Medical history of physician-confirmed infection with an A/California/7/2009 (H1N1)v-like virus
* Previous vaccination at any time with an H1N1v-like virus vaccine or a medical history of physician-confirmed infection with an H1N1v-like virus.
* Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, even if stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.
* Presence of a temperature \>= 38.0ºC (\>=100.4ºF), or acute symptoms greater than "mild" severity on the scheduled date of first vaccination.
* Diagnosed with cancer, or treatment for cancer, within 3 years.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
* Receipt of systemic glucocorticoids within 1 month prior to study enrollment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrollment. Topical, intra-articularly injected, or inhaled glucocorticoids, topical calcineurin inhibitors or imiquimod are allowed.
* 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 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 acetylsalicylic acid, and without a clinically-apparent bleeding tendency, are eligible.
* An acute evolving neurological disorder or history of Guillain-Barré syndrome within 6 weeks of receipt of seasonal influenza vaccine
* With the exception of seasonal influenza vaccination, administration of any vaccine(s) within 30 days before study vaccination on Day 0. Seasonal influenza vaccine may be administered up to 14 days prior to study vaccination on Day 0.
* Planned administration of any vaccine not foreseen by the study protocol between Day 0 and the Day 42 phlebotomy, including seasonal influenza vaccine or a monovalent pandemic H1N1 vaccine other than the study vaccines.
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine/product, or planned use during the study period.
* 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.
* Known pregnancy or a positive urine beta-human chorionic gonadotropin test result prior to the first vaccination.
* Lactating or nursing women.

Primary outcomes:
measure: Number of Subjects Seropositive for Haemagglutination Inhibition (HI) Antibodies Against the A/California Virus Strain
timeFrame: At Day 0
measure: Number of Subjects Seropositive for Haemagglutination Inhibition (HI) Antibodies Against the A/California Virus Strain
timeFrame: At Day 21
measure: Number of Subjects Seropositive for (HI) Antibodies Against the A/California Virus Strain
timeFrame: At Day 0
measure: Number of Subjects Seropositive for (HI) Antibodies Against the A/California Virus Strain
timeFrame: At Day 21
measure: Number of Seroconverted (SCR) Subjects for Haemagglutination Inhibition (HI) Antibodies Against A/California Virus Strain
timeFrame: At Day 21
measure: Number of Seroconverted (SCR) Subjects for HI Antibodies Against A/California Strain
timeFrame: At Day 21
measure: Number of Seroprotected (SPR) Subjects for HI Antibodies Against A/California Virus Strain
timeFrame: At Day 0
measure: Number of Seroprotected (SPR) Subjects for HI Antibodies Against A/California Virus Strain
timeFrame: At Day 21
measure: Number of Seroprotected (SPR) Subjects for HI Antibodies Against A/California Strain
timeFrame: At Day 0
measure: Number of Seroprotected (SPR) Subjects for HI Antibodies Against A/California Strain
timeFrame: At Day 21
measure: Seroconversion Factor (SCF) for Haemagglutination Inhibition (HI) Antibodies Against A/California Virus Strain
timeFrame: At Day 21
measure: Seroconversion Factor (SCF) for HI Antibodies Against A/California Strain
timeFrame: At Day 21
Secondary outcomes:
measure: Number of Subjects Seropositive for HI Antibodies Against A/California Virus Strain
timeFrame: At Days 0 and 21
measure: Titers for HI Antibodies Against A/California Strain
timeFrame: At Days 0 and 21
measure: Number of Seroconverted (SCR) Subjects for HI Antibodies Against A/California Virus Strain
timeFrame: At Day 21
measure: Number of Seroprotected (SPR) Subjects Against HI Antibodies for the A/California Virus Strain
timeFrame: At Days 0 and 21
measure: Seroconversion Factor (SCF) for HI Antibodies Against A/California Virus Strain
timeFrame: At Day 21
measure: Number of Subjects Seropositive for HI Antibodies Against the A/California Virus Strain
timeFrame: At Days 0 and 42
measure: Titers for HI Antibodies Against the A/California Virus Strain
timeFrame: At Days 0 and 42
measure: Number of Seroconverted (SCR) Subjects for HI Antibodies Against A/California Virus Strain
timeFrame: At Day 42
measure: Number of Seroprotected (SPR) Subjects for HI Antibodies Against A/California Strain
timeFrame: At Days 0 and 42
measure: Seroconversion Factor (SCF) for HI Antibodies Against A/California Virus Strain
timeFrame: At Day 42
measure: Number of Subjects Seropositive for HI Antibodies Against the A/California Virus Strain
timeFrame: At Days 0 and 182
measure: Titers for HI Antibodies Against the A/California Virus Strain
timeFrame: At Days 0 and 182
measure: Number of Seroconverted (SCR) Subjects for HI Antibodies
timeFrame: At Day 182
measure: Number of Seroprotected (SPR) Subjects for HI Antibodies Against A/California Virus Strain
timeFrame: At Days 0 and 182
measure: Seroconversion Factor (SCF) for HI Antibodies Against A/California Virus Strain
timeFrame: At Day 182
measure: Adjusted Geometric Mean Titer (GMT) Ratios of A/California Virus Strain
timeFrame: At Day 21
measure: Adjusted Geometric Mean Titer (GMT) Ratios of A/California Strain
timeFrame: At Day 21
measure: Adjusted GMT Ratios of A/California Virus Strain
timeFrame: At Day 21
measure: Adjusted GMT Ratios of A/California Strain
timeFrame: At Day 21
measure: Adjusted GMT Ratios for A/California Virus Strain
timeFrame: At Day 21
measure: Adjusted GMT Ratios for A/California Strain
timeFrame: At Day 21
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses, for subjects between 18-64 years of age
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day (Day 0-6) post-vaccination period following each dose and across doses, for subjects > 64 years of age
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day (Day 0-6) post-vaccination period following each dose and across doses, for subjects between 18-64 years of age
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day (Day 0-6) post-vaccination period following each dose and across doses, for subjects > 64 years of age
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) post-Dose 3 vaccination period, for subjects > 60 years of age
measure: Number of Subjects With Any and Grade 3 Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) post-Dose 3 vaccination period, for subjects > 60 years of age
measure: Number of Subjects With Abnormal Biochemical and Haematological Levels
timeFrame: At Days 7, 21, 28, 42 and 182, for subjects between 18-64 years of age
measure: Number of Subjects With Abnormal Biochemical and Haematological Levels
timeFrame: At Days 7, 21, 28, 42 and 182, for subjects > 64 years of age
measure: Number of Subjects With Any Medically-attended Adverse Events (MAEs)
timeFrame: Days 0 to 385
measure: Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs)
timeFrame: Days 0 to 365
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: Within the 42-day (Days 0-41) post-vaccination period
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: Within the 84-day (Days 0-83) post-vaccination period
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the entire study period (from Day 0 to Day 385)
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: GSK Investigational Site
state: Alabama
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Meridian
country: United States
facility: GSK Investigational Site
state: Idaho
city: Lenexa
country: United States
facility: GSK Investigational Site
state: Kansas
city: Missoula
country: United States
facility: GSK Investigational Site
state: Montana
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Edison
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Surrey
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Truro
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Pointe-Claire
country: Canada
facility: GSK Investigational Site
state: Quebec
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Ferguson M, Risi G, Davis M, Sheldon E, Baron M, Li P, Madariaga M, Fries L, Godeaux O, Vaughn D. Safety and long-term humoral immune response in adults after vaccination with an H1N1 2009 pandemic influenza vaccine with or without AS03 adjuvant. J Infect Dis. 2012 Mar 1;205(5):733-44. doi: 10.1093/infdis/jir641.