Study to Determine the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals; Infanrix Hexa at 2, 4 and 6 Months of Age in Healthy Infants

Hepatitis B Clinical Trial

Official title:

Immunogenicity and Safety Study of GSK Biologicals' Infanrix Hexa at 2, 4 and 6 Months of Age in Healthy Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02096263
• Other study ID #: 117119
• Secondary ID: 2013-004304-19
• Status: Completed
• Phase: Phase 3
• Start date: April 16, 2014
• Est. completion date: November 13, 2015

Study information

• Verified date: November 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the immunogenicity and safety of GSK Biologicals' Infanrix hexa vaccine when administered to healthy infants as primary vaccination at 2, 4 and 6 months of age, co-administered with Prevnar and Rotarix with a booster dose of GSK Biologicals' Infanrix and Hiberix vaccines at 15-18 months of age.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 585
• Est. completion date: November 13, 2015
• Est. primary completion date: February 6, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Weeks to 12 Weeks

Eligibility

Inclusion Criteria:

• Subjects' parent(s)/ Legally Acceptable Representative(s) (LARs) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol.

• A male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination.

• Born full-term (i.e. after a gestation period of 37 weeks to less than 42 completed weeks [259 to 293 days]).

• Written informed consent obtained from parent(s)/LAR(s) of the subject.

• Healthy subjects as established by medical history and clinical examination before entering into the study.

• Infants who have not received a previous dose of hepatitis B vaccine or those who have received only 1 dose of hepatitis B vaccine administered at least 30 days prior to enrolment.

Exclusion Criteria:

• Child in care

• 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 vaccines, or planned use during the study period.

• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, this will mean prednisone = 0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.

• Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting from 30 days before the first vaccination until 30 days after Dose 3 (Epoch 001, primary vaccination) and from 30 days before the booster Dose 4 until 30 days after booster Dose 4 (Epoch 002, booster vaccination), i.e. the end of the study:

• Inactivated influenza and hepatitis A vaccines are allowed throughout the study.

• Routine administration(s) of vaccines are allowed from 30 days after the last dose of primary vaccination until 30 days before the booster dose and after post-booster blood sampling. Routine administration of measles-mumps-rubella vaccine, varicella, pneumococcal vaccines are allowed from 30 days after last dose of primary vaccine until 30 days before booster dose and from post-booster blood sampling, as well as according to the recommended immunization schedule in US.

• 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 (pharmaceutical product or device).

• History of Hib, diphtheria, tetanus, pertussis, pneumococcal, rotavirus, poliovirus and hepatitis B diseases.

• Previous vaccination against Hib, diphtheria, tetanus, pertussis, pneumococcus, rotavirus and/or poliovirus; more than one previous dose of hepatitis B vaccine.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).

• Family history of congenital or hereditary immunodeficiency.

• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines (including yeast).

• Hypersensitivity to latex.

• Major congenital defects or serious chronic illness.

• History of any neurological disorders including seizures.

• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

• History of intussusception or of any uncorrected congenital malformation of the gastrointestinal tract that would predispose the infant to intussusception.

• History of Severe Combined Immunodeficiency Disease (SCID).

• Acute disease and/or fever at the time of enrolment.

• Fever is defined as temperature =38.0°C /100.4°F by any route. The preferred route for recording temperature in this study will be rectal for Epoch 001 and axillary for Epoch 002.

• Subjects with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.

Related Conditions & MeSH terms

• Acellular Pertussis
• Diphtheria
• Haemophilus Influenzae Type b
• Hepatitis B
• Poliomyelitis
• Tetanus

Intervention

Biological:
• Infanrix hexa
3 doses administered intramuscularly in the right thigh.
• Pediarix
3 doses administered intramuscularly in the right thigh
• ActHIB
4 doses administered intramuscularly in the upper left thigh
• Pentacel
4 doses administered intramuscularly in the right thigh
• Engerix-B
2 or 3 doses administered intramuscularly in the upper left thigh
• Infanrix
1 dose administered intramuscularly in the right thigh
• Hiberix
1 dose administered intramuscularly in the left thigh
• Prevnar13
3 doses administered intramuscularly in the lower left thigh
• Rotarix
2 doses administered orally

Locations

Country	Name	City	State
United States	GSK Investigational Site	Altamonte Springs	Florida
United States	GSK Investigational Site	Anaheim	California
United States	GSK Investigational Site	Augusta	Kansas
United States	GSK Investigational Site	Charlottesville	Virginia
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Columbia	Maryland
United States	GSK Investigational Site	Daly City	California
United States	GSK Investigational Site	Dayton	Ohio
United States	GSK Investigational Site	Ellensburg	Washington
United States	GSK Investigational Site	Erie	Pennsylvania
United States	GSK Investigational Site	Fayetteville	Arkansas
United States	GSK Investigational Site	Fresno	California
United States	GSK Investigational Site	Hayward	California
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	Kingsport	Tennessee
United States	GSK Investigational Site	Layton	Utah
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Marietta	Georgia
United States	GSK Investigational Site	Nampa	Idaho
United States	GSK Investigational Site	Newton	Kansas
United States	GSK Investigational Site	Nicholasville	Kentucky
United States	GSK Investigational Site	Oakland	California
United States	GSK Investigational Site	Orange City	Florida
United States	GSK Investigational Site	Payson	Utah
United States	GSK Investigational Site	Pleasanton	California
United States	GSK Investigational Site	Provo	Utah
United States	GSK Investigational Site	Roseville	California
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Saint George	Utah
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	San Jose	California
United States	GSK Investigational Site	Santa Clara	California
United States	GSK Investigational Site	Sellersville	Pennsylvania
United States	GSK Investigational Site	South Jordan	Utah
United States	GSK Investigational Site	Syracuse	New York
United States	GSK Investigational Site	Topeka	Kansas
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Walnut Creek	California
United States	GSK Investigational Site	West Jordan	Utah
United States	GSK Investigational Site	Wichita	Kansas
United States	GSK Investigational Site	Woodstock	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

References & Publications (1)

Klein NP, Abu-Elyazeed R, Cheuvart B, Janssens W, Mesaros N. Immunogenicity and safety following primary and booster vaccination with a hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b vaccine: a randomized trial in the United States. Hum Vaccin Immunother. 2019;15(4):809-821. doi: 10.1080/21645515.2018.1549449. Epub 2019 Jan 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antibody Concentrations for Pertussis Toxoid (Anti-PT), Filamentous Hemagglutinin (Anti-FHA) and Pertactin (Anti-PRN).	Concentrations were expressed as geometric mean concentrations (GMCs) for the following cut-offs:2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, and 2.187 IU/mL for anti-PRN. The results for the Infanrix hexa Group and Pediarix Group were the primary outcome variables.	At Month 5, one month after the third dose of the primary vaccination.
Secondary	Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN.	A seropositive subject was defined as a subject with antibody concentrations above to or equal to (=) 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, and 2.187 IU/mL for anti-PRN.	At Month 5, one month after the third dose of the primary vaccination.
Secondary	Number of Seroprotected Subjects Against Tetanus (T).	A seroprotected subject was defined a a subject with antibody concentrations = 0.1 IU/mL.	At Month 5, one month after the third dose of the primary vaccination.
Secondary	Number of Seroprotected Subjects Against Diphtheria (D).	A seroprotected subject was defined a a subject with antibody concentrations = 0.1 IU/mL.	At Month 5, one month after the third dose of the primary vaccination.
Secondary	Antibody Concentrations for Anti-T.	Concentrations were expressed as GMCs for the seroprotection cut-off of 0.1 IU/mL.	At Month 5, one month after the third dose of the primary vaccination
Secondary	Antibody Concentrations for Anti-D.	Concentrations were expressed as GMCs for the seroprotection cut-off of 0.1 IU/mL.	At Month 5, one month after the third dose of the primary vaccination
Secondary	Number of Seroprotected Subjects Against Anti-polio Types 1, 2 and 3.	A seroprotected subject was defined as a subject with anti-polio types 1, 2 and 3 titres = 8 dilution.	At Month 5, one month after the third dose of the primary vaccination
Secondary	Antibody Titres for Anti-polio Types 1, 2 and 3.	Titres were expressed as geometric mean titres (GMTs) for the cut-off of 8 dilution.	At Month 5, one month after the third dose of the primary vaccination
Secondary	Number of Seroprotected Subjects Against Polyribosyl Ribitol Phosphate (Anti-PRP).	A seroprotected subject was defined as a subject with anti-PRP concentrations = 0.15 µg/mL.	At Month 5, one month after the third dose of the primary vaccination
Secondary	Number of Subjects With Anti-PRP Antibody Concentrations = 1 µg/mL.	The cut-off for this assay was an anti-PRP concentration = 1 µg/mL.	At Month 5, one month after the third dose of the primary vaccination
Secondary	Antibody Concentrations for Anti-PRP.	Antibody concentrations were expressed as GMCs for the assay cut-off of 1 µg/mL.	At Month 5, one month after the third dose of the primary vaccination
Secondary	Number of Seroprotected Subjects Against Hepatitis B (Anti-HBs).	A seroprotected subject was defined as a subject with anti-HBs antibody concentrations = 10 mili-International units per mililiter (mIU/mL).	At Month 5, one month after the third dose of the primary vaccination
Secondary	Antibody Concentrations for Anti-HBs.	Antibody concentrations were expressed as GMCs for the seroprotection cut-off of 10 mIU/mL.	At Month 5, one month after the third dose of the primary vaccination
Secondary	Number of Subjects With Solicited Local Symptoms.	The solicited local symptoms assessed were pain, redness and swelling. Any = any reports of the specific symptom irrespective of intensity grade; above or equal (=); Grade 2 Redness/Swelling: > 5 millimeters (mm); Grade 3 Redness/Swelling: > 20 mm; Grade 2 Pain = Moderate: cries/protests on touch; Grade 3 Pain = Severe: Cries when limb is moved/spontaneously painful. Grade = G; Medical Advice = MA.	During the 4-day (Days 0-3) post-vaccination period following Dose 1
Secondary	Number of Subjects With Solicited Local Symptoms.	The solicited local symptoms assessed were pain, redness (Red) and swelling (Swe). Any = any reports of the specific symptom irrespective of intensity grade; above or equal (=); Grade 2 Redness/Swelling: > 5 millimeters (mm); Grade 3 Redness/Swelling: > 20 mm; Grade 2 Pain = Moderate: cries/protests on touch; Grade 3 Pain = Severe: Cries when limb is moved/spontaneously painful. Grade = G; Medical Advice = MA.	During the 4-day (Days 0-3) post-vaccination period following Dose 2
Secondary	Number of Subjects With Solicited Local Symptoms.	The solicited local symptoms assessed were pain, redness and swelling. Any = any reports of the specific symptom irrespective of intensity grade; above or equal (=); Grade 2 Redness/Swelling: > 5 millimeters (mm); Grade 3 Redness (Red)/Swelling (Swe): > 20 mm; Grade 2 Pain = Moderate: cries/protests on touch; Grade 3 Pain = Severe: Cries when limb is moved/spontaneously painful. Grade = G; Medical Advice = MA	During the 4-day (Days 0-3) post-vaccination period following Dose 3
Secondary	Number of Subjects With Solicited Local Symptoms.	The solicited local symptoms assessed were pain, redness and swelling. Any = any reports of the specific symptom irrespective of intensity grade; above or equal (=); Grade 2 Redness (Red)/Swelling (Swe): > 5 millimeters (mm); Grade 3 Redness/Swelling: > 20 mm; Grade 2 Pain = Moderate: cries/protests on touch; Grade 3 Pain = Severe: Cries when limb is moved/spontaneously painful. Grade = G; Medical Advice = MA.	During the 4-day (Days 0-3) post-vaccination period following any dose.
Secondary	Number of Subjects With Solicited General Symptoms.	The solicited general symptoms assessed were Drowsiness, Irritability/Fussiness, Loss Of Appetite and Fever (defined as temperature = 38.0°C). Any = any reports of the specific symptom irrespective of intensity grade; Grade 2 (G2) Drowsiness = Drowsiness that interfered with normal activity; Grade 2 Irritability/Fussiness = Moderate: Cried more than usual/interfered with normal activity; Grade 2 Loss of appetite = Ate less than usual/interfered with normal activity; Grade 2 Fever: > 39.0 °C; Grade 3 (G3) Drowsiness/Irritability/Fussiness = symptom that prevented normal activity; Grade 3 Loss of appetite = Did not eat at all; Grade 3 Fever: > 40.0 °C; Related (Rel) = Symptom which was assessed by the investigator as related to vaccination.	During the 4-day (Days 0-3) post-vaccination period following Dose 1.
Secondary	Number of Subjects With Solicited General Symptoms.	The solicited general symptoms assessed were Drowsiness, Irritability/Fussiness, Loss Of Appetite and Fever (defined as temperature = 38.0°C). Any = any reports of the specific symptom irrespective of intensity grade; Grade 2 (G2) Drowsiness = Drowsiness that interfered with normal activity; Grade 2 Irritability/Fussiness = Moderate: Cried more than usual/interfered with normal activity; Grade 2 Loss of appetite = Ate less than usual/interfered with normal activity; Grade 2 Fever: > 39.0 °C; Grade 3 (G3) Drowsiness/Irritability/Fussiness = symptom that prevented normal activity; Grade 3 Loss of appetite = Did not eat at all; Grade 3 Fever: > 40.0 °C; Related (Rel) = Symptom which was assessed by the investigator as related to vaccination.	During the 4-day (Days 0-3) post-vaccination period following Dose 2.
Secondary	Number of Subjects With Solicited General Symptoms.	The solicited general symptoms assessed were Drowsiness, Irritability/Fussiness, Loss Of Appetite and Fever (defined as temperature = 38.0°C). Any = any reports of the specific symptom irrespective of intensity grade; Grade 2 (G2) Drowsiness = Drowsiness that interfered with normal activity; Grade 2 Irritability/Fussiness = Moderate: Cried more than usual/interfered with normal activity; Grade 2 Loss of appetite = Ate less than usual/interfered with normal activity; Grade 2 Feve:r > 39.0 °C; Grade 3 (G3) Drowsiness/Irritability/Fussiness = symptom that prevented normal activity; Grade 3 Loss of appetite = Did not eat at all; Grade 3 Fever: > 40.0 °C; Related (Rel) = Symptom which was assessed by the investigator as related to vaccination.	During the 4-day (Days 0-3) post-vaccination period following Dose 3.
Secondary	Number of Subjects With Solicited General Symptoms.	The solicited general symptoms assessed were Drowsiness, Irritability/Fussiness, Loss Of Appetite and Fever (defined as temperature = 38.0°C). Any = any reports of the specific symptom irrespective of intensity grade; Grade 2 (G2) Drowsiness = Drowsiness that interfered with normal activity; Grade 2 Irritability/Fussiness = Moderate: Cried more than usual/interfered with normal activity; Grade 2 Loss of appetite = Ate less than usual/interfered with normal activity; Grade 2 Fever: > 39.0 °C; Grade 3 (G3) Drowsiness/Irritability/Fussiness = symptom that prevented normal activity; Grade 3 Loss of appetite = Did not eat at all; Grade 3 Fever: > 40.0 °C; Related (Rel) = Symptom which was assessed by the investigator as related to vaccination.	During the 4-day (Days 0-3) post-vaccination period following any dose.
Secondary	Number of Subjects With Specific Adverse Events (AEs).	Occurrence of specific adverse events, i.e., new onset chronic diseases (e.g. autoimmune disorders, asthma, type I diabetes and allergies)	From Month 0 up to 6 months post primary-vaccination (Month 10)
Secondary	Number of Subjects With Unsolicited AEs.	An unsolicited AE is any AE (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.	During the 31-day (Days 0-30) post-primary vaccination period.
Secondary	Number of Subjects With Serious Adverse Events (SAEs).	SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.	From Month 0 up to 6 months post-primary vaccination (Month 10)
Secondary	Number of Seroprotected Subjects Against Anti-T.	A seroprotected subject was defined a subject with antibody concentrations = 0.1 IU/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)] and at Visit 6 (At Month 14-17 one month after the booster dose (Dose 4)]
Secondary	Number of Seroprotected Subjects Against Anti-D.	A seroprotected subject was defined a subject with antibody concentrations = 0.1 IU/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)] and at Visit 6 (At Month 14-17 one month after the booster dose (Dose 4)]
Secondary	Antibody Concentrations for Anti-T.	Concentrations were expressed as GMCs for the seropositivity cut-off of 0.1 IU/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)] and at Visit 6 [At Month 14-17 one month after the booster dose (Dose 4)]
Secondary	Antibody Concentrations for Anti-D.	Concentrations were expressed as GMCs for the seropositivity cut-off of 0.1 IU/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)] and at Visit 6 [At Month 14-17 one month after the booster dose (Dose 4)]
Secondary	Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN.	A seropositive subject was defined as a subject with antibody concentrations above to or equal to (=) 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, and 2.187 IU/mL for anti-PRN.	At Visit 5 [Month 13-16 before the booster dose (Dose 4)] and at Visit 6 [Month 14-17 one month after the booster dose (Dose 4)]
Secondary	Antibody Concentrations for Anti-PT, Anti-FHA and Anti-PRN.	Concentrations were expressed as geometric mean concentrations (GMCs) for the following cut-offs:2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, and 2.187 IU/mL for anti-PRN.	At Visit 5 [Month 13-16 before the booster dose (Dose 4)] and at Visit 6 [Month 14-17 one month after the booster dose (Dose 4)]
Secondary	Number of Subjects With a Booster Response for Anti-PT, Anti-FHA and Anti-PRN.	Booster response to PT, FHA and PRN antigens was defined as: For subjects with pre-vaccination antibody concentration below the assay cut off, post-vaccination antibody concentration equal or above 4 times the assay cut-off.; For subjects with pre-vaccination antibody concentration between the assay cut off and below 4 times the assay cut-off, post-vaccination antibody concentration equal or above 4 times the pre-vaccination antibody concentration.; For subjects with pre-vaccination antibody concentration equal or above 4 times the assay cut-off, post-vaccination antibody concentration of at least two times the pre-vaccination antibody concentration.; The assay cut off is 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, and 2.187 IU/mL for anti-PRN.	At Visit 6 [At Month 14-17 one month after the booster dose (Dose 4)]
Secondary	Number of Seroprotected Subjects Against Anti-PRP.	A seroprotected subject was defined as a subject with anti-PRP concentrations = 0.15 µg/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)] and at Visit 6 [At Month 14-17 one month after the booster dose (Dose4)]
Secondary	Number of Subjects With Anti-PRP Antibody Concentrations = 1 µg/mL.	The cut-off for this assay was an anti-PRP concentration = 1 µg/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)] and at Visit 6 [At Month 14-17 one month after the booster dose (Dose4)]
Secondary	Antibody Concentrations for Anti-PRP.	Antibody concentrations were expressed as GMCs for the seroprotection cut-off of 1 µg/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)] and at Visit 6 [At Month 14-17 one month after the booster dose (Dose 4)]
Secondary	Number of Seroprotected Subjects Against Anti-polio Types 1, 2 and 3.	A seroprotected subject was defined as a subject with anti-polio types 1, 2 and 3 titres = 8 dilution.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)]
Secondary	Antibody Titres for Anti-polio Types 1, 2 and 3.	Titres were expressed as geometric mean titres (GMTs) for the cut-off of 8 dilution.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)]
Secondary	Number of Seroprotected Subjects Against Anti-HBs.	A seroprotected subject was defined as a subject with anti-HBs antibody concentrations = 10 mIU/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)]
Secondary	Antibody Concentrations for Anti-HBs.	Antibody concentrations were expressed as GMCs for the seroprotection cut-off of 10 mIU/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)]
Secondary	Number of Subjects With Solicited Local Symptoms.	The solicited local symptoms assessed were pain, redness and swelling. Any = any reports of the specific symptom irrespective of intensity grade; above or equal (=); Grade 2 Redness (Red)/Swelling (Swe): > 5 millimeters (mm); Grade 3 Redness/Swelling: > 20 mm; Grade 2 Pain = Moderate: cries/protests on touch; Grade 3 Pain = Severe: Cries when limb is moved/spontaneously painful. Grade = G; Medical Advice = MA.	During the 4-day (Days 0-3) post-booster vaccination.
Secondary	Number of Subjects With Solicited General Symptoms.	The solicited general symptoms assessed were Drowsiness, Irritability/Fussiness, Loss Of Appetite and Fever (defined as temperature = 38.0°C). Any = any reports of the specific symptom irrespective of intensity grade; Grade 2 (G2) Drowsiness = Drowsiness that interfered with normal activity; Grade 2 Irritability/Fussiness = Moderate: Cried more than usual/interfered with normal activity; Grade 2 Loss of appetite = Ate less than usual/interfered with normal activity; Grade 2 Fever: > 39.0 °C and = 40.0 °C; Grade 3 (G3) Drowsiness/Irritability/Fussiness = symptom that prevented normal activity; Grade 3 Loss of appetite = Did not eat at all; Grade 3 Fever: > 40.0 °C; Related (Rel) = Symptom which was assessed by the investigator as related to vaccination.	During the 4-day (Days 0-3) post-booster vaccination.
Secondary	Number of Subjects With Specific AEs.	Occurrence of specific adverse events, i.e., new onset chronic diseases (e.g. autoimmune disorders, asthma, type I diabetes and allergies)	During the 31-day (Days 0-30) post-booster vaccination.
Secondary	Number of Subjects With Unsolicited AEs.	An unsolicited AE is any AE (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.	During the 31-day (Days 0-30) post-booster vaccination.
Secondary	Number of Subjects With SAEs.	SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.	During the 31-day (Days 0-30) post-booster vaccination.

External Links

•   Full CSR redacted with additional report posting on GSK.