Safety and Immune Response of Candidate H1N1 Influenza Vaccine GSK2340274A Following Seasonal Influenza Vaccination in Adults

GlaxoSmithKline133 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

133

Conditions

Influenza

Interventions

GSK Biologicals' FluLaval®BIOLOGICAL

Intramuscular injection

Placebo (saline)BIOLOGICAL

Intramuscular injection

GSK Biologicals' investigational H1N1 Influenza Vaccine - GSK2340274ABIOLOGICAL

Intramuscular injections

Eligibility

Sex: ALLMin age: 19 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (3)

GSK Investigational Site

Milford, Massachusetts, United States

GSK Investigational Site

Salisbury, North Carolina, United States

GSK Investigational Site

Winston-Salem, North Carolina, United States

Outcomes

Primary Outcomes

Number of Seroconverted Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

Seroconversion rate (SCR) was defined as the number of subjects who have either a pre-vaccination reciprocal HI titer \< 10 and a post-vaccination reciprocal titer ≥ 40, or a pre-vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus.

Time frame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).

Number of Seroprotected Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

Seroprotection rate (SPR) was defined as the number of subjects with H1N1 reciprocal HI titers ≥ 40 against the tested vaccine virus.

Time frame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).

Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

Geometric mean fold-rise (GMFR), or seronversion factor (SCF), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus.

Time frame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 122 to Day 164).

Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

A seropositive subject was a subject whose HI antibody titer was greater than or equal to the assay cut-off value of 1:10.

Time frame: 21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).

Titers for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

A seropositive subject was a subject whose HI antibody titer was greater than or equal to the assay cut-off value of 1:10.

Time frame: At Day 122 and Day 304

Titers for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

Titers were expressed as geometric mean antibody titers (GMTs).

Time frame: At Days 122 and 304

Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Titers Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

VRR for microneutralization titers was defined as the incidence rate of vaccinees with at least a 4-fold increase in post vaccination reciprocal titer relative to Day 0. The cut-off value for microneutralization titers is 1:28.

Time frame: Entire study period up to Day 507

Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

A seropositive subject was a subject whose HI antibody titer was greater than or equal to the assay cut-off value of 1:10.

Time frame: At Days 0 and 304

Titers for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

Titers were expressed as geometric mean antibody titers (GMTs).

Time frame: At Day 0 and Day 304

Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Titers Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

Time frame: For the entire study period up to Day 507

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

CD4 T cell-mediated immune responses against the antigens A/California/7/2009, A/Brisbane/59/2007 and A/Uruguay/716/2007 were analyzed for cells expressing at least 2 of the following immune markers: CD40 Ligand, Interleukin-2, Tumor Necrosis Factor alpha or Interferon-gamma. The frequency was presented as number of cytokine-producing CD4+ cells per million CD4+ cells. All doubles= T cell expressing at least 2 cytokines. Subjects with missing results were not included.

Time frame: Before administration of Arepanrix vaccine (Day 0 to Day 122)

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

CD4 T cell-mediated immune responses against the antigens A/California/7/2009, A/Brisbane/59/2007 and A/Uruguay/716/2007 were analyzed for cells expressing at least 2 of the following immune markers: CD40 Ligand, Interleukin2, Tumor Necrosis Factor alpha or Interferongamma. The frequency was presented as number of cytokineproducing CD4+ cells per million CD4+ cells. All doubles= T cell expressing at least 2 cytokines.

Time frame: After the administration of Arepanrix vaccine (Day 125 to 304)

Number of Subjects Reporting Any and Related Potential Immune-mediated Disease (pIMDs).

pIMDs are a subset of adverse events (AEs) that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Related = symptom assed by the investigator as causally related to the study vaccination.

Time frame: During the entire study period (up to Day 507).

Number of Subjects Reporting Any and Related Medically Attended Adverse Events (MAEs).

MAEs refer to events that required medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. Related = symptom assed by the investigator as causally related to the study vaccination.

Time frame: During the entire study period (up to Day 507).

Number of Subjects Reporting Unsolicited AEs.

An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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. Unsolicited AEs were collected after the administration of the Flulaval vaccine or the placebo dose and the data has been pooled based on the vaccination received at Day 0.

Time frame: Up to 21-day (Days 0-20) after vaccination

Number of Subjects Reporting Unsolicited AEs.

Unsolicited AEs were collected after the administration of the Arepanrix or the unadjuvanted formulation of Arepanrix vaccine. An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.

Time frame: Within 84 days following first dose or 63 days following second dose of vaccine.

Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs).

SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. Related = symptom assed by the investigator as causally related to the study vaccination.

Time frame: During the entire study period (up to Day 507).

Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs).

Time frame: Up to Day 234

Number of Subjects Reporting Any and Related Medically Attended Adverse Events (MAEs).

Time frame: Within Days 0-233

Number of Subjects Reporting Any and Related Potential Immune-mediated Disease (pIMDs).

Time frame: Within Days 0-233

Number of Subjects Reporting Solicited Local Symptoms From Flulaval Group and Placebo Group.

Solicited local symptoms assessed were pain, redness and swelling and data collected was pooled by administration of vaccination received at Day 0 (i.e. Flulaval or Saline placebo). Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal activity. Grade 3 redness and swelling were defined as redness/swelling above 100 millimeter (mm).

Time frame: During the 7-day (Days 0-6) follow-up period after vaccination.

Number of Subjects Reporting Solicited General Symptoms From Flulaval Group and Placebo Group.

Solicited general symptoms assessed were fatigue, headache, joint pain at other location, muscle aches, shivering, sweating and temperature (= axillary temperature equal to or above 38.0 degrees Celsius (°C)) and data collected was pooled by administration of vaccination received at Day 0 (i.e. Flulaval or Saline placebo). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature above 39.0°C.

Time frame: During the 7-day (Days 0-6) follow-up period after vaccination.

Number of Subjects Reporting Solicited Local Symptoms From Flulaval/Arepanrix Group,Flulaval/Unadjuvanted Arepanrix Group,Placebo/Arepanrix Group and Placebo/Unadjuvanted Arepanrix Group

Solicited local symptoms assessed were pain, redness and swelling and were collected after the administration of the Arepanrix or the unadjuvanted formulation of Arepanrix vaccine. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal activity. Grade 3 redness and swelling were defined as redness/swelling above 100 millimeter (mm).

Time frame: During the 7-day (Days 0-6) follow-up period after vaccination.

Number of Subjects Reporting Solicited General Symptoms From Flulaval/Arepanrix Group,Flulaval/Unadjuvanted Arepanrix Group, Placebo/Arepanrix Group and Placebo/Unadjuvanted Arepanrix Group.

Solicited general symptoms assessed were fatigue, headache, joint pain at other location, muscle aches, shivering, sweating and temperature (= axillary temperature equal to or above 38.0 degrees Celsius (°C)) and were collected after the administration of the Arepanrix or the unadjuvanted formulation of Arepanrix vaccine. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature above 39.0°C.

Time frame: During the 7-day (Days 0-6) follow-up period after vaccination.

Number of Subjects Reporting Clinical Laboratory Abnormalities in Haematological Parameters Assessed With Respect to Normal Laboratory Ranges.

Laboratory parameters assessed were white blood cells (WBC), neutrophils (NEU), lymphocytes (LYM), monocytes (MON), eosinophils (EOS), basophils (BAS), red blood cells (RBC), hemoglobin (Hgb), hematocrit (Hct) and platelets (PLA). For each parameter and for each status at baseline it was assessed whether the post-vaccination values of the parameter were above, below or within the range (unkown values are also indicated).

Time frame: On Days 0, 21, 122 and 164

Number of Subjects Reporting Clinical Laboratory Abnormalities in Biochemistry Parameters Assessed With Respect to Normal Laboratory Ranges.

Laboratory parameters assessed were alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatise (AP), creatinine (CREA), blood urea nitrogen (BUN) and bilirubin (BIL) (total (T) and direct (D)). For each parameter and for each status at baseline it was assessed whether the post-vaccination values of the parameter were above, below or within the range (unkown values are also indicated).

Time frame: On Days 0, 21, 122 and 164

Number of Subjects Reporting Clinical Laboratory Abnormalities in Haematological Parameters Assessed With Respect to Normal Laboratory Ranges.

Time frame: At Day 304

Number of Subjects Reporting Clinical Laboratory Abnormalities in Biochemistry Parameters Assessed With Respect to Normal Laboratory Ranges.

Laboratory parameters assessed were alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (AP), creatinine (CREA), blood urea nitrogen (BUN), and bilirubin (BIL) (total (T) and direct (D)). For each parameter and for each status at baseline it was assessed whether the post-vaccination values of the parameter were above, below or within the range (unkown values are also indicated).

Time frame: At Day 304

Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

A seropositive subject was a subject whose HI antibody titer was greater than or equal to the assay cut-off value of 1:10. Seropositivity rates of H1N1 HI antibody titers in terms of humoral immune response was pooled by the vaccination received at Day 0 (i.e. Flulaval or Saline placebo) at Days 7, 14 and 21 upto the administration of the first dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccine.

Time frame: Before vaccination and at Days 7, 14, 21 and 122

Titers for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

Titers were expressed as geometric mean antibody titers (GMTs). GMTs of H1N1 HI antibody titers in terms of humoral immune response was pooled by the vaccination received at Day 0 (i.e. Flulaval or Saline placebo) at Days 7, 14, 21 and 122 upto the administration of the first dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccine.

Time frame: Before vaccination and at Days 7, 14, 21 and 122

Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

A seropositive subject was a subject whose HI antibody titer was greater than or equal to the assay cut-off value of 1:10.

Time frame: At Days 122, 129, 136, 143, 150, 157 and 164.

Titers for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

Titers were expressed as geometric mean antibody titers (GMTs).

Time frame: At Days 122, 129, 136, 143, 150, 157 and 164.

Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

A seropositive subject was a subject whose HI antibody titer was greater than or equal to the assay cut-off value of 1:10. Seropositivity rates of H1N1 HI antibody titers in terms of humoral immune response was pooled by the vaccination received at Day 0 (i.e. Flulaval or Saline placebo) at Days 7, 14, 21 and 122 upto the administration of the first dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccine.

Time frame: Before vaccination and at Days 7, 14, 21 and 122

Titers for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

Time frame: Before vaccination and at Days 7, 14, 21 and 122

Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

A seropositive subject was a subject whose HI antibody titer was greater than or equal to the assay cut-off value of 1:10.

Time frame: At Days 122, 129, 136, 143, 150, 157 and 164.

Titers for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

Titers were expressed as geometric mean antibody titers (GMTs).

Time frame: At Days 122, 129, 136, 143, 150, 157 and 164.