Clinical trial NCT00985673: Safety and Immunogenicity of H1N1 Vaccine With Trivalent Inactivated Seasonal Influenza Vaccine in Adults
Official title: A Study to Evaluate the Safety and Immunogenicity of an A/California/7/2009 (H1N1)V-like Vaccine GSK2340274A or GSK2340273A Co-administered With Trivalent Inactivated Seasonal Influenza Vaccine in Adults 19 to 40 Years of Age
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: 611
Sex: ALL
Minimum age (years): 19
Maximum age (years): 40
Standard ages: 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 GSK2340274A and GSK2340273A when co-administered with the seasonal flu vaccine in adults 19 to 40 years of age.

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 or female adults, 19-40 years of age at the time of the first vaccination.
* Safety laboratory tests results within the parameters specified in the protocol.
* Satisfactory baseline medical assessment by 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:

* Previous vaccination with an H1N1v-like virus vaccine or a medical history of physician-confirmed infection with an H1N1v-like virus.
* Prior receipt at any time of any seasonal influenza vaccine.
* Planned administration of any vaccine not foreseen by the study protocol between Day 0 and the Day 63 phlebotomy.
* Administration of any licensed vaccine within 4 weeks before the first study vaccine dose.
* Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Receipt of systemic glucocorticoids within one month prior to study enrolment, or any other cytotoxic or immunosuppressive drug within six months of study enrolment. Topical, intra-articularly injected, or inhaled glucocorticoids, topical calcineurin inhibitors or imiquimod are allowed.
* Receipt of any immunoglobulins and/or any blood products within three months of study enrolment or planned administration of any of these products during the study period.
* 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.
* 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 six weeks of receipt of seasonal influenza vaccine.
* 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 first vaccination.
* Lactating or nursing women.

Primary outcomes:
measure: Hemagglutination Inhibition (HI) Antibody Titers Against A/California/7/2009 H1N1 Vaccine Strain.
timeFrame: 21 days after the second dose of Arepanrix vaccine (at Day 42).
measure: Hemagglutination Inhibition (HI) Antibody Titers Against A/California/7/2009 H1N1 Vaccine Strain.
timeFrame: 21 days after the second dose of the unadjuvanted formulation of Arepanrix vaccine (at Day 42)
Secondary outcomes:
measure: Number of Influenza-specific Cluster of Differentiation 4 (CD4) T-cells Per Million Producing Two or More Markers Within Cluster Differentiation 40 Ligand (CD40L), Interleukin-2 (IL-2), Interferon-γ (IFN-γ) and Tumor Necrosis Factor-α (TNF-α).
timeFrame: On Days 0, 7, 21, 28, 42, 63 and 182
measure: Number of Influenza-specific Cluster of Differentiation 8 (CD8) T-cells Per Million Producing Two or More Markers Within Cluster Differentiation 40 Ligand (CD40L), Interleukin-2 (IL-2), Interferon-γ (IFN-γ) and Tumor Necrosis Factor-α (TNF-α).
timeFrame: On Days 0, 7, 21, 28, 42, 63 and 182
measure: Number of Subjects Reporting Clinical Laboratory Abnormalities in Biochemical and Haematological Parameters Assessed
timeFrame: On Days 0, 7, 21, 28, 42, 63 and 182
measure: Number of Subjects Reporting Clinical Laboratory Abnormalities in Biochemical and Haematological Parameters Assessed
timeFrame: On Days 0, 7, 21, 28, 42, 63 and 182
measure: Number of Subjects Reporting Solicited Local Symptoms.
timeFrame: During a 7-day follow-up period (Days 0-6) post-vaccination period
measure: Number of Subjects Reporting Solicited General Symptoms.
timeFrame: During a 7-day follow-up period (Days 0-6) post-vaccination period
measure: Number of Subjects Reporting Clinical Laboratory Abnormalities in Biochemical and Haematological Parameters Assessed
timeFrame: On Days 0, 7, 21, 28, 42, 63 and 182
measure: Number of Subjects Reporting Unsolicited Adverse Events (AEs).
timeFrame: Within the 84-day (Days 0-83) post-vaccination period.
measure: Number of Subjects Reporting Medically Attended Visits (MAEs).
timeFrame: During the entire study period (Days 0-368).
measure: Number of Subjects Reporting Potential Immune Diseases (pIMDs).
timeFrame: During the entire study period (Days 0-406).
measure: Number of Subjects Reporting Serious Adverse Events (SAEs).
timeFrame: During the entire study period (Days 0-329).
measure: Number of Subjects Reporting Clinical Laboratory Abnormalities in Biochemical and Haematological Parameters Assessed
timeFrame: On Days 0, 7, 21, 28, 42, 63 and 182
measure: Microneutralization Antibody Titers Against A/California/7/2009 (H1N1) Strain.
timeFrame: On Days 0, 21, 42, 63 and 182
measure: Number of Subjects With a Microneutralization Titer Greater Than or Equal to 1:28 for Antibodies Against A/California/7/2009 (H1N1) Strain.
timeFrame: On Days 0, 21, 42, 63 and 182
measure: Vaccine Response Rates (VRR) for Microneutralization Antibody Titers Against A/California/7/2009 (H1N1) Strain.
timeFrame: On Days 0, 21, 42, 63 and 182
measure: Hemagglutination Inhibition (HI) Antibody Titers Against A/California/7/2009 H1N1 Vaccine Strain.
timeFrame: 21 days after the second dose of Arepanrix vaccine (Day 63 for Flulaval/placebo/Arepanrix Group and Day 42 for Arepanrix/placebo/Flulaval Group)
measure: Hemagglutination Inhibition (HI) Antibody Titers Against A/California/7/2009 H1N1 Vaccine Strain.
timeFrame: 21 days after the second dose of the unadjuvanted formulation of Arepanrix vaccine (Day 63 for Flulaval/placebo/unadjuvanted Arepanrix Group and Day 42 for Unadjuvanted Arepanrix/placebo/Flulaval Group)
measure: Hemagglutination Inhibition (HI) Antibody Titers Against A/California/7/2009 H1N1 Vaccine Strain.
timeFrame: 21 days after the second dose of the pandemic vaccine (at Day 63)
measure: Hemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Flulaval Strains.
timeFrame: 21 days after the Flulaval vaccination (at Day 21).
measure: Hemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Flulaval Strains.
timeFrame: 21 days after the Flulaval vaccination (at Day 21).
measure: Hemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Flulaval Strains.
timeFrame: 21 days after the Flulaval vaccination (Day 63 for Arepanrix/placebo/Flulaval Group and Day 21 for Flulaval/placebo/unadjuvanted Arepanrix and Flulaval/placebo/Arepanrix Groups)
measure: Hemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Flulaval Strains.
timeFrame: 21 days after the Flulaval vaccination (Day 63 for Unadjuvanted Arepanrix/placebo/Flulaval Group and Day 21 for Flulaval/placebo/unadjuvanted Arepanrix and Flulaval/placebo/Arepanrix Groups)
measure: Geometric Mean Antibody Titers (GMTs) for Hemagglutination Inhibition (HI) Antibodies Against Flu A/California H1N1 Strain.
timeFrame: On Days 0, 21, 42 and 63
measure: Geometric Mean Antibody Titers (GMTs) for Hemagglutination Inhibition (HI) Antibodies Against Flu A/California H1N1 Strain.
timeFrame: At Day 182
measure: Number of Seroconverted Subjects for Antibodies Against A/ California Strain.
timeFrame: At Day 63 from Day 21 for Flulaval/placebo/unadjuvanted Arepanrix and Flulaval/placebo/Arepanrix Groups; At Day 42 from Day 0 for the 4 other groups
measure: Number of Seroprotected Subjects for Antibodies Against A/California Strain.
timeFrame: At Day 63 for Flulaval/placebo/unadjuvanted Arepanrix and Flulaval/placebo/Arepanrix Groups; At Day 42 for the 4 other groups.
measure: Seroconversion Factor for Antibodies Against A/California Strain.
timeFrame: At Day 63 from Day 21 for Flulaval/placebo/unadjuvanted Arepanrix and Flulaval/placebo/Arepanrix Groups; At Day 42 from Day 0 for the 4 other groups
measure: Number of Seroconverted Subjects for Antibodies Against Flulaval Vaccine Strains.
timeFrame: At Day 21 from Day 0 for the pooled group, Flulaval/unadjuvanted Arepanrix/placebo and Flulaval/Arepanrix/placebo Groups; at Day 63 from Day 42 for Unadjuvanted Arepanrix/placebo/Flulaval Group and Arepanrix/placebo/Flulaval Group
measure: Number of Seroprotected Subjects for Antibodies Against Flulaval Vaccine Strains
timeFrame: At Day 21 for the pooled group, Flulaval/unadjuvanted Arepanrix/placebo and Flulaval/Arepanrix/placebo Groups; at Day 63 for Unadjuvanted Arepanrix/placebo/Flulaval Group and Arepanrix/placebo/Flulaval Group
measure: Seroconversion Factor for Antibodies Against Flulaval Vaccine Strains.
timeFrame: At Day 21 from Day 0 for the pooled group, Flulaval/unadjuvanted Arepanrix/placebo and Flulaval/Arepanrix/placebo Groups; at Day 63 from Day 42 for Unadjuvanted Arepanrix/placebo/Flulaval Group and Arepanrix/placebo/Flulaval Group
measure: Number of Seroconverted Subjects for Antibodies Against Flulaval Vaccine Strains
timeFrame: on Days 21 and 63 from Day 0 for the first 4 groups; on Days 42 and 63 from Day 0 for the Unadjuvanted Arepanrix/placebo/Flulaval and Arepanrix/placebo/Flulaval Groups
measure: Number of Seroconverted Subjects for Antibodies Against Flulaval Vaccine Strains
timeFrame: At Day 182 from Day 0
measure: Number of Seroprotected Subjects for Antibodies Against Flulaval Vaccine Strains.
timeFrame: before vaccination and on days 21 and 63 for the first 4 groups and before vaccination and on days 42 and 63 for the Unadjuvanted Arepanrix/placebo/Flulaval and Arepanrix/placebo/Flulaval Groups
measure: Number of Seroprotected Subjects for Antibodies Against Flulaval Vaccine Strains.
timeFrame: At Day 182 after the first dose
measure: Seroconversion Factor for Antibodies Against Flulaval Vaccine Strains.
timeFrame: On Days 21 and 63 from Day 0 for the first 4 groups and on Days 42 and 63 from Day 0 for the Unadjuvanted Arepanrix/placebo/Flulaval and Arepanrix/placebo/Flulaval Groups
measure: Seroconversion Factor for Antibodies Against Flulaval Vaccine Strains.
timeFrame: At Day 182 from Day 0
measure: Geometric Mean Antibody Titers (GMTs) for Hemagglutination Inhibition (HI) Antibodies Against Flulaval Vaccine Strains.
timeFrame: On Days 0, 21 and 63 for the first 4 groups and on Days 0, 42 and 63 for the Unadjuvanted Arepanrix/placebo/Flulaval and Arepanrix/placebo/Flulaval Groups
measure: Geometric Mean Antibody Titers (GMTs) for Hemagglutination Inhibition (HI) Antibodies Against Flulaval Vaccine Strains.
timeFrame: At Day 182 after dose 1 vaccination
Other outcomes:
Locations:
city: Stockbridge
country: United States
facility: GSK Investigational Site
state: Georgia
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
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:
citation: Friel D, Co M, Ollinger T, Salaun B, Schuind A, Li P, Walravens K, Ennis FA, Vaughn DW. Non-neutralizing antibody responses following A(H1N1)pdm09 influenza vaccination with or without AS03 adjuvant system. Influenza Other Respir Viruses. 2021 Jan;15(1):110-120. doi: 10.1111/irv.12780. Epub 2020 Sep 5.
citation: Langley JM, Frenette L, Chu L, McNeil S, Halperin S, Li P, Vaughn D. A randomized, controlled non-inferiority trial comparing A(H1N1)pmd09 vaccine antigen, with and without AS03 adjuvant system, co-administered or sequentially administered with an inactivated trivalent seasonal influenza vaccine. BMC Infect Dis. 2012 Oct 30;12:279. doi: 10.1186/1471-2334-12-279.