Clinical trial NCT01059617: Safety and Immune Response of Candidate H1N1 Influenza Vaccine GSK2340274A Following Seasonal Influenza Vaccination in Adults
Official title: A Study to Evaluate Immune Responses Following A/California/7/2009 (H1N1)V-like Virus Vaccination Given 4 Months Following Seasonal Influenza Vaccination in Adults 19 to 40 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza
Keywords: Pandemic
GSK Bio's influenza vaccine GSK2340274A
H1N1
Influenza
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-02-01
Enrollment: 133
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: This study is designed to characterize the safety and immunogenicity of a' pandemic influenza (H1N1) candidate vaccine GSK2340274A in adults 19 to 40 years who have never received influenza vaccination.


Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits).
* Written informed consent obtained from the subject.
* Male or female adults, 19-40 years of age at the time of the first vaccination.
* Body weight of at least 110 pounds (49.9 kg).
* Safety laboratory tests results within the parameters specified by protocol.
* Satisfactory baseline medical assessment by physical examination (stable health status with no exclusionary conditions). Stable health status is defined as the 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 one month prior to enrollment.
* 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 (i.e., a common-use phone serving multiple rooms or apartments).
* Female subjects of non-childbearing potential may be enrolled in the study.
* Non-childbearing potential is defined as current tubal ligation, hysterectomy, ovariectomy, or post-menopause.
* 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 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 A/California/7/2009 (H1N1)v-like virus vaccine
* A medical history of physician-confirmed infection with an A/California/7/2009 (H1N1)v-like virus.
* Prior receipt at any time of any seasonal influenza vaccine.
* Planned administration of any vaccine not foreseen by the study protocol (including any influenza vaccine other than the study vaccine) between Days 0 and the Day 164 phlebotomy.
* Administration of any licensed vaccine within 30 days before the first study vaccine dose.
* Use of any investigational or non-registered product (drug or vaccine) 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 (e.g., prednisone ≥ 0.5 mg/kg/day, or ≥ 10 mg/day \[whichever is less\] for more than 14 consecutive days) 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 9 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.
* History of anemia.
* Presence of a temperature ≥ 38.0ºC (≥100.4ºF), (oral temperature assessment preferred), 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 is required.)
* 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 any vaccine.
* 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 any vaccine.
* Known pregnancy or a positive urine beta-human chorionic gonadotropin (β-HCG) test result prior to first vaccination.
* Lactating or nursing women.

Primary outcomes:
measure: Number of Seroconverted Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.
timeFrame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).
measure: Number of Seroprotected Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.
timeFrame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).
measure: Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.
timeFrame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 122 to Day 164).
measure: Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.
timeFrame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).
measure: Titers for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.
timeFrame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).
measure: Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Titers Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.
timeFrame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).
measure: Number of Seroconverted Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.
timeFrame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).
measure: Number of Seroprotected Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.
timeFrame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).
measure: Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.
timeFrame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 122 to Day 164).
measure: Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.
timeFrame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).
measure: Titers for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.
timeFrame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).
measure: Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Titers Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.
timeFrame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).
Secondary outcomes:
measure: Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.
timeFrame: At Day 122 and Day 304
measure: Titers for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.
timeFrame: At Days 122 and 304
measure: Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Titers Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.
timeFrame: Entire study period up to Day 507
measure: Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.
timeFrame: At Days 0 and 304
measure: Titers for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.
timeFrame: At Day 0 and Day 304
measure: Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Titers Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.
timeFrame: For the entire study period up to Day 507
measure: Cell-mediated Immunogenicity (CMI) in Terms of T-cell Markers Related to A/California/7/2009, A/Brisbane/59/2007, B/Brisbane/59/2007 and A/Uruguay/716/2007 Antigens
timeFrame: Before administration of Arepanrix vaccine (Day 0 to Day 122)
measure: Cell-mediated Immunogenicity (CMI) in Terms of Tcell Markers Related to A/California/7/2009, A/Brisbane/59/2007, B/Brisbane/59/2007 and A/Uruguay/716/2007 Antigens
timeFrame: After the administration of Arepanrix vaccine (Day 125 to 304)
measure: Number of Subjects Reporting Any and Related Potential Immune-mediated Disease (pIMDs).
timeFrame: During the entire study period (up to Day 507).
measure: Number of Subjects Reporting Any and Related Medically Attended Adverse Events (MAEs).
timeFrame: During the entire study period (up to Day 507).
measure: Number of Subjects Reporting Unsolicited AEs.
timeFrame: Up to 21-day (Days 0-20) after vaccination
measure: Number of Subjects Reporting Unsolicited AEs.
timeFrame: Within 84 days following first dose or 63 days following second dose of vaccine.
measure: Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs).
timeFrame: During the entire study period (up to Day 507).
measure: Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs).
timeFrame: Up to Day 234
measure: Number of Subjects Reporting Any and Related Medically Attended Adverse Events (MAEs).
timeFrame: Within Days 0-233
measure: Number of Subjects Reporting Any and Related Potential Immune-mediated Disease (pIMDs).
timeFrame: Within Days 0-233
measure: Number of Subjects Reporting Solicited Local Symptoms From Flulaval Group and Placebo Group.
timeFrame: During the 7-day (Days 0-6) follow-up period after vaccination.
measure: Number of Subjects Reporting Solicited General Symptoms From Flulaval Group and Placebo Group.
timeFrame: During the 7-day (Days 0-6) follow-up period after vaccination.
measure: Number of Subjects Reporting Solicited Local Symptoms From Flulaval/Arepanrix Group,Flulaval/Unadjuvanted Arepanrix Group,Placebo/Arepanrix Group and Placebo/Unadjuvanted Arepanrix Group
timeFrame: During the 7-day (Days 0-6) follow-up period after vaccination.
measure: Number of Subjects Reporting Solicited General Symptoms From Flulaval/Arepanrix Group,Flulaval/Unadjuvanted Arepanrix Group, Placebo/Arepanrix Group and Placebo/Unadjuvanted Arepanrix Group.
timeFrame: During the 7-day (Days 0-6) follow-up period after vaccination.
measure: Number of Subjects Reporting Clinical Laboratory Abnormalities in Haematological Parameters Assessed With Respect to Normal Laboratory Ranges.
timeFrame: On Days 0, 21, 122 and 164
measure: Number of Subjects Reporting Clinical Laboratory Abnormalities in Biochemistry Parameters Assessed With Respect to Normal Laboratory Ranges.
timeFrame: On Days 0, 21, 122 and 164
measure: Number of Subjects Reporting Clinical Laboratory Abnormalities in Haematological Parameters Assessed With Respect to Normal Laboratory Ranges.
timeFrame: At Day 304
measure: Number of Subjects Reporting Clinical Laboratory Abnormalities in Biochemistry Parameters Assessed With Respect to Normal Laboratory Ranges.
timeFrame: At Day 304
measure: Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.
timeFrame: Before vaccination and at Days 7, 14, 21 and 122
measure: Titers for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.
timeFrame: Before vaccination and at Days 7, 14, 21 and 122
measure: Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.
timeFrame: At Days 122, 129, 136, 143, 150, 157 and 164.
measure: Titers for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.
timeFrame: At Days 122, 129, 136, 143, 150, 157 and 164.
measure: Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.
timeFrame: Before vaccination and at Days 7, 14, 21 and 122
measure: Titers for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.
timeFrame: Before vaccination and at Days 7, 14, 21 and 122
measure: Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.
timeFrame: At Days 122, 129, 136, 143, 150, 157 and 164.
measure: Titers for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.
timeFrame: At Days 122, 129, 136, 143, 150, 157 and 164.
Other outcomes:
Locations:
city: Milford
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Salisbury
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: GSK Investigational Site
state: North Carolina
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: