Immunogenicity and Safety of PrepandrixTM in Korean Subjects Aged 18 to 60 Years Old

Immunogenicity and Safety of GlaxoSmithKline Biologicals' (Pre-) Pandemic Influenza Vaccine Prepandrix™ in Korean Subjects Aged 18 to 60 Years Old

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01730378

Enrollment

131

Registered

2012-11-21

Start date

2012-12-05

Completion date

2013-12-17

Last updated

2018-09-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Influenza

Keywords

Influenza vaccine

Brief summary

This study will evaluate the immunogenicity and the safety of PrepandrixTM in Korean subjects. A second group of subjects will receive FluarixTM vaccine as control.

Detailed description

Initially, 124 subjects were planned to be enrolled according to a 1:1 randomisation ratio. However, by mistake, the randomisation application was set up consistent with the vaccine supply ratio (2:1) rather than the treatment group randomization ratio (1:1). Subsequently, the protocol was amended to adjust the sample size and randomisation ratio for the study. The study will enrol 126 subjects randomised 2:1. 84 subjects will receive Prepandrix™ and 42 subjects will receive Fluarix™.

Interventions

BIOLOGICALPrepandrix™

2 doses administered intramuscularly in the deltoid region of arm (non-dominant arm at Day 0 and dominant arm at Day 21).

BIOLOGICALFluarix™

1 dose administered intramuscularly in the deltoid region of non-dominant arm.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Yes

Inclusion criteria

* Subjects who the investigator believes can and will comply with the requirements of the protocol. Or subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) can and will comply with the requirements of the protocol. * Korean male or female subject between, and including, 18 and 60 years of age at the time of the first vaccination. * Written informed consent obtained from the subject/ from the parent(s)/ Legally Acceptable Representative(s). * Healthy subjects or free of acute aggravation of the health status as established by medical history and clinical examination before entering into the study. * 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, has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception during the entire treatment period and for two months after completion of the vaccination series.

Exclusion criteria

* 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. * Acute disease and/or fever at the time of enrollment. * Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. * Diagnosed with cancer, or treatment for cancer, within the past three years. * Any confirmed or suspected immunosuppressive or immunodeficient condition, including history of human immunodeficiency virus (HIV) infection. * Family history of congenital or hereditary immunodeficiency. * 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 aspirin, and without any clinically-apparent bleeding tendency, are eligible. * History of any neurological disorders or seizures. * An acute evolving neurological disorder or history of Guillan-Barré syndrome. * Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. * Any administration of long-acting immune-modifying drugs within three months before study start, or a planned administration during the study period. * Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period. * Clinically or virologically diagnosed influenza infection within six months preceding the study start. * Administration of any vaccines within 30 days before vaccination, or planned administration during the study start. * Previous vaccination against influenza with any seasonal or pandemic vaccine within six months preceding the administration of the study vaccine. * Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product. * History of allergy or reactions likely to be exacerbated by any component of the vaccines, including history of a severe adverse reaction to a previous dose of influenza vaccine. * Female planning to become pregnant or planning to discontinue contraceptive precautions. * Child in care.

Design outcomes

Primary

Measure	Time frame	Description
Number of Seroconverted Subjects for Serum H5N1 Haemagglutination-inhibition (HI) Antibodies Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	At Day 42	A seroconverted subjects was defined as a vaccinated subject with either a pre-vaccination titer less than (\<) 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer.
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	At Day 42	MGI was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination (Day 0).
Number of Subjects Who Were Seroprotected for Anti-HI Antibodies Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	At Day 42	A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults.
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	At Day 0 and Day 42	Antibody titers were expressed as Geometric mean titers (GMTs).

Secondary

Measure	Time frame	Description
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	At Days 0 and 21	Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Victoria/361/2011 (H3N2) and Flu B/Hubei-Wujiagang/158/2009 (Yamagata).
Number of Seroconverted Subjects for HI Antibodies Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	At Day 21	A seroconverted subjects was defined as a vaccinated subject with either a pre-vaccination titer less than (\<) 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Victoria/361/2011 (H3N2)and Flu B/Hubei-Wujiagang/158/2009 (Yamagata).
Mean Geometric Increase (MGI) for HI Antibodies Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	At Day 21	MGI was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Victoria/361/2011 (H3N2) and Flu B/Hubei-Wujiagang/158/2009 (Yamagata).
Number of Subjects Who Were Seroprotected for HI Antibodies Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	At Day 0 and Day 21	A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Victoria/361/2011 (H3N2) and Flu B/Hubei-Wujiagang/158/2009 (Yamagata).
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.	During the 7-day (Day 0-6) period after each vaccination	Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as significant pain at rest that prevented normal everyday activities as assessed by inability to attend/do work or school. Grade 3 redness and swelling was greater than 100 millimeters (mm) i.e. \>100mm.
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	At Day 21	Antibody titers were expressed as Geometric mean titers (GMTs).
Number of Subjects Reporting Any Potential Immune Mediated Diseases (pIMDs).	During the entire study period (From Day 0 to Day 182)	Potential immune-mediated diseases (pIMDs) were defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
Number of Subjects Reporting Unsolicited Adverse Events (AEs)	During the 21 days (Day 0-20) post-vaccination period	Unsolicited AE covers any AE 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. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.
Number of Subjects Reporting Unsolicted AEs	During the 84-day (Days 0-83) post vaccination period	Unsolicited AE covers any AE 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. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.
Number of Subjects Any Unsolicited AEs	During the 63-day (Days 21-83) post-dose 2 in Prepandrix Group	Unsolicited AE covers any AE 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. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.
Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs)	During the entire study period (From Day 0 to 182)	A serious adverse event was any untoward medical occurrence that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.	During the 7-day (Days 0-6) post-vaccination period	Solicited general symptoms assessed were fatigue, headache, joint pain, muscle aches, shivering, increased sweating and fever \[axillary temperature above 38.0 degrees Celsius (°C)\]. 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 as assessed by inability to attend/do work or school, or requires intervention of a physician/healthcare provider. Grade 3 fever = axillary temperature above 39.0°C
Number of Subjects Who Were Seroprotected for HI Antibodies Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	At Day 0 and Day 21	A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults.
Number of Seroconverted Subjects for HI Antibodies Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	At Day 21	A seroconverted subjects was defined as a vaccinated subject with either a pre-vaccination titer less than (\<) 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer.
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	At Day 21	MGI was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination (Day 0).

Countries

South Korea

Participant flow

Participants by arm

Arm	Count
Prepandrix Group Subjects in this group received 2 doses of Prepandrix™ vaccine at Days 0 and 21. The vaccine was administered intramuscularly in the deltoid region of arm (non-dominant arm at Day 0 and dominant arm at Day 21).	84
Fluarix Group Subjects in this group received 1 dose of Fluarix™ vaccine at Day 0. The vaccine was administered intramuscularly in the deltoid region of non-dominant arm.	47
Total	131

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	1	0

Baseline characteristics

Characteristic	Prepandrix Group	Fluarix Group	Total
Age, Continuous	39.3 Years STANDARD_DEVIATION 10.94	40.4 Years STANDARD_DEVIATION 10.3	39.69 Years STANDARD_DEVIATION 10.69
Sex: Female, Male Female	61 Participants	34 Participants	95 Participants
Sex: Female, Male Male	23 Participants	13 Participants	36 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	81 / 84	40 / 47
serious Total, serious adverse events	1 / 84	0 / 47

Outcome results

Primary

Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.

Antibody titers were expressed as Geometric mean titers (GMTs).

Time frame: At Day 0 and Day 42

Population: Analysis was performed on the ATP cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome variables were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Prepandrix Group	Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	H5N1, Day 0	5.2 Titer
Prepandrix Group	Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	H5N1, Day 42	300.1 Titer

Primary

Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.

MGI was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination (Day 0).

Time frame: At Day 42

Arm	Measure	Value (GEOMETRIC_MEAN)
Prepandrix Group	Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	58.0 Fold increase

Primary

Number of Seroconverted Subjects for Serum H5N1 Haemagglutination-inhibition (HI) Antibodies Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.

Time frame: At Day 42

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome variables were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component after vaccination.

Arm	Measure	Value (NUMBER)
Prepandrix Group	Number of Seroconverted Subjects for Serum H5N1 Haemagglutination-inhibition (HI) Antibodies Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	81 Subjects

Primary

Number of Subjects Who Were Seroprotected for Anti-HI Antibodies Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.

A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults.

Time frame: At Day 42

Arm	Measure	Value (NUMBER)
Prepandrix Group	Number of Subjects Who Were Seroprotected for Anti-HI Antibodies Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	81 Subjects

Secondary

Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.

Antibody titers were expressed as Geometric mean titers (GMTs).

Time frame: At Day 21

Arm	Measure	Value (GEOMETRIC_MEAN)
Prepandrix Group	Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	31.8 Titer

Secondary

Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.

Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Victoria/361/2011 (H3N2) and Flu B/Hubei-Wujiagang/158/2009 (Yamagata).

Time frame: At Days 0 and 21

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Prepandrix Group	Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	H1N1, Day 0	18.3 Titer
Prepandrix Group	Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	H1N1, Day 21	425.9 Titer
Prepandrix Group	Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	H3N2, Day 0	22.0 Titer
Prepandrix Group	Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	H3N2, Day 21	149.2 Titer
Prepandrix Group	Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	Yamagata, Day 0	60.1 Titer
Prepandrix Group	Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	Yamagata, Day 21	367.6 Titer

Secondary

Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.

MGI was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination (Day 0).

Time frame: At Day 21

Arm	Measure	Value (GEOMETRIC_MEAN)
Prepandrix Group	Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	6.2 Fold increase

Secondary

Mean Geometric Increase (MGI) for HI Antibodies Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.

MGI was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Victoria/361/2011 (H3N2) and Flu B/Hubei-Wujiagang/158/2009 (Yamagata).

Time frame: At Day 21

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Prepandrix Group	Mean Geometric Increase (MGI) for HI Antibodies Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	H1N1	23.3 Fold increase
Prepandrix Group	Mean Geometric Increase (MGI) for HI Antibodies Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	H3N2	6.8 Fold increase
Prepandrix Group	Mean Geometric Increase (MGI) for HI Antibodies Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	Yamagata	6.1 Fold increase

Secondary

Number of Seroconverted Subjects for HI Antibodies Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.

A seroconverted subjects was defined as a vaccinated subject with either a pre-vaccination titer less than (\<) 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Victoria/361/2011 (H3N2)and Flu B/Hubei-Wujiagang/158/2009 (Yamagata).

Time frame: At Day 21

Arm	Measure	Group	Value (NUMBER)
Prepandrix Group	Number of Seroconverted Subjects for HI Antibodies Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	H1N1	33 Subjects
Prepandrix Group	Number of Seroconverted Subjects for HI Antibodies Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	H3N2	24 Subjects
Prepandrix Group	Number of Seroconverted Subjects for HI Antibodies Against Each of the Three Vaccine Seasonal Influenza Strains in Fluarix Group.	Yamagata	26 Subjects

Secondary

Number of Seroconverted Subjects for HI Antibodies Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.

Time frame: At Day 21

Arm	Measure	Value (NUMBER)
Prepandrix Group	Number of Seroconverted Subjects for HI Antibodies Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group.	37 Subjects

Secondary

Number of Subjects Any Unsolicited AEs

Unsolicited AE covers any AE 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. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.

Time frame: During the 63-day (Days 21-83) post-dose 2 in Prepandrix Group

Arm	Measure	Value (NUMBER)
Prepandrix Group	Number of Subjects Any Unsolicited AEs	16 Subjects

Secondary

Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.

Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as significant pain at rest that prevented normal everyday activities as assessed by inability to attend/do work or school. Grade 3 redness and swelling was greater than 100 millimeters (mm) i.e. \>100mm.

Time frame: During the 7-day (Day 0-6) period after each vaccination