Safety and Immunogenicity Study of GlaxoSmithKline (GSK)... | NCT02184572

NCT02184572

ID	Type	Description	Link
2011-006161-18	EudraCT Number

Status Module

Description Module

Label	Type	Description	Intervention Names
INV_MMR	Experimental	Subjects receive 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also receive Prevnar 13 at Day 0.	Biological: Priorix Biological: Varivax Biological: Havrix Biological: Prevnar 13
COM_MMR	Active Comparator	Subjects receive 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also receive Prevnar 13 at Day 0.	Biological: M-M-R II Biological: Varivax Biological: Havrix Biological: Prevnar 13

Name	Type	Description	Arm Group Labels	Other Names
Priorix	Biological	1 dose administered subcutaneously in the triceps region of left arm at Day 0	INV_MMR

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Subjects Reporting Fever After MMR (Priorix or M-M-R II/M-M-R VaxPro [Lot 1 or Lot 2]) Vaccination	Fever was assessed for temperature equal to/above (≥) 38.0°C and above (>) 39.0°C. The safety profile for fever was assessed based on the group difference (INV_MMR minus COM_MMR) in incidence of fever equal to or below the cut-off value.	During Day 5 to Day 12 post-vaccination period

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value	Seroresponse was defined as post-vaccination anti-measles virus antibody concentration greater than or equal to [≥] 200 milli International Units per milliliter [mIU/mL] (Enzyme-Linked Immunosorbent Assay [ELISA], Enzygnost) among subjects who were seronegative (antibody concentration less than [<] 150 mIU/mL) before vaccination.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female child between 12 and 15 months of age (e.g., from the 1 year birthday until the day before age 16 months) at the time of vaccination.
Subjects' parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol.
Written informed consent obtained from the parent(s)/LAR(s) of the child.
Child is in stable health as determined by investigator's clinical examination and assessment of child's medical history.
For US children only: a child who received all routine vaccinations as per ACIP recommendations prior to study entry: completion of hepatitis B and rotavirus series and completion of the primary series of diphtheria, tetanus, pertussis, poliovirus, Haemophilus influenzae type b (Hib) and pneumococcal vaccines. The 3-dose infant series of Prevnar 13 should be completed at least 60 days prior to study vaccination.

Exclusion Criteria:

Child in care.
Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) during the period starting 30 days before the day of study vaccination (i.e., 30 days prior to Day 0) or planned use during the entire study period.
Concurrently participating in another clinical study, in which the child has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
Chronic administration (defined as 14 or more consecutive days) of immunosuppressants, or other immune-modifying drugs during the period starting 180 days prior to the study vaccination at Visit 1 or any planned administration of immunosuppressive and immune-modifying drugs during the entire study.
- 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 during the period starting 30 days prior to the day of study vaccination at Visit 1 and ending at Visit 2. Please Note:
- Inactivated influenza (Flu) vaccine and monovalent Haemophilus influenzae type b conjugate vaccine (Hib) vaccines may be given at any time, including the day of study vaccination (Flu and Hib vaccines must be administered at a different location than the study vaccine/s).
- Any other age appropriate vaccine may be given starting at Visit 2 and anytime thereafter.
Administration of immunoglobulins and/or any blood products during the period starting 180 days before the study vaccination at Visit 1 or planned administration from the date of vaccination through the immunogenicity evaluation at Visit 2.
History of measles, mumps, rubella, varicella/zoster and/or hepatitis A disease.
Known exposure to measles, mumps, rubella and/or varicella/zoster during the period starting within 30 days prior to first study vaccination.
Previous vaccination against measles, mumps, rubella, hepatitis A and/or varicella virus.
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
Blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems.
A family history of congenital or hereditary immunodeficiency.
History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, including hypersensitivity to neomycin, latex or gelatin.
Acute disease at the time of enrollment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever). Fever is defined as temperature ≥38.0°C/100.4°F by any age appropriate route. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection without fever.
Active untreated tuberculosis based on medical history.
Any other condition which, in the opinion of the investigator, prevents the child from participating in the study.
For US children only: a child that previously received a fourth dose of PCV-13 vaccine.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Birmingham	Alabama	35205	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
30118386	Background	MMR-162 Study Group. Safety and immunogenicity of an upper-range release titer measles-mumps-rubella vaccine in children vaccinated at 12 to 15 months of age: a phase III, randomized study. Hum Vaccin Immunother. 2018;14(12):2921-2931. doi: 10.1080/21645515.2018.1502527. Epub 2018 Aug 29.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	INV_MMR	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
FG001	COM_MMR

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Subjects Reporting Fever After MMR (Priorix or M-M-R II/M-M-R VaxPro [Lot 1 or Lot 2]) Vaccination

Fever was assessed for temperature equal to/above (≥) 38.0°C and above (>) 39.0°C. The safety profile for fever was assessed based on the group difference (INV_MMR minus COM_MMR) in incidence of fever equal to or below the cut-off value.

Analysis was performed on Total Vaccinated cohort (TVC) which included all vaccinated subjects with administration of either Priorix or M-M-R II/M-M-R VaxPro lots documented.

Posted

Count of Participants

Participants

During Day 5 to Day 12 post-vaccination period

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Units	Counts
Participants	OG0001126 OG001555

Title

Denominators

Categories

> 39.0°C

Title	Measurements
	OG00047 OG00117

≥ 38.0°C

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Difference between groups (INV_MMR Group minus COM_MMR Group) in incidence of fever > 39.0°C.					Difference in incidence of fever	1.11			2-Sided	95	-0.93	2.89					Non-Inferiority or Equivalence (legacy)	The upper limit of the 2-sided standardised asymptotic 95% Confidence Interval (CI) for the group difference (INV_MMR minus COM_MMR) in incidence of fever ≥ 39.0°C (≥ 102.2°F) should be equal to or below 5%.

Secondary

Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value

Seroresponse was defined as post-vaccination anti-measles virus antibody concentration greater than or equal to [≥] 200 milli International Units per milliliter [mIU/mL] (Enzyme-Linked Immunosorbent Assay [ELISA], Enzygnost) among subjects who were seronegative (antibody concentration less than [<] 150 mIU/mL) before vaccination.

According to Protocol (ATP) cohort for immunogenicity: included all eligible subjects with pre and post-vaccination serology results available for at least one vaccine components of measles, mumps or rubella, who did not meet any elimination criteria up to the Visit 2 blood sample and who complied with the post dose blood sample schedule.

Posted

Number

95% Confidence Interval

Percentage of subjects

At Day 42 post vaccination

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Secondary

Anti-measles Virus Antibody Concentrations

Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. Analyses included initially seronegative subjects only.

ATP cohort for immunogenicity: included all eligible subjects with pre and post-vaccination serology results available for at least one vaccine components of measles, mumps or rubella, who did not meet any elimination criteria up to the Visit 2 blood sample and who complied with the post dose blood sample schedule.

Posted

Geometric Mean

95% Confidence Interval

mIU/mL

At Day 42 post vaccination

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Units	Counts
Participants

Secondary

Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value

Seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 10 ELISA Unit per milliliter [EU/mL] (ELISA, Pharmaceutical Product Development, Inc.[PPD]) among subjects who were seronegative (antibody concentration < 5 EU/mL) before vaccination.

Posted

Number

95% Confidence Interval

Percentage of subjects

At Day 42 post vaccination

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Secondary

Anti-mumps Virus Antibody Concentrations

Antibody concentrations were expressed as GMCs in EU/mL. Analyses included initially seronegative subjects only.

According to Protocol (ATP) cohort for immunogenicity: included all eligible subjects with pre and post-vaccination serology results available for at least one vaccine components of measles, mumps, or rubella, who did not meet any elimination criteria up to the Visit 2 blood sample and who complied with the post dose blood sample schedule.

Posted

Geometric Mean

95% Confidence Interval

EU/mL

At Day 42 post vaccination

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Units	Counts
Participants

Secondary

Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value

Seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥ 10 International Unit per milliliter [IU/mL] (ELISA, Enzygnost) among subjects who were seronegative (antibody concentration < 4 IU/mL) before vaccination.

Posted

Number

95% Confidence Interval

Percentage of subjects

At Day 42 post vaccination

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Secondary

Anti-rubella Virus Antibody Concentrations

Antibody concentrations were expressed as GMCs in IU/mL. Analyses included initially seronegative subjects only.

Posted

Geometric Mean

95% Confidence Interval

IU/mL

At Day 42 post vaccination

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Units	Counts
Participants

Secondary

Number of Subjects With Any Solicited Local Adverse Events (AEs)

Assessed solicited local AEs were injection site pain, redness and swelling. Any = Occurrence of AE regardless of intensity grade or relation to vaccination.

Analysis was performed on TVC which included all vaccinated subjects with administration of either Priorix or M-M-R II/M-M-R VaxPro lots documented.

Posted

Count of Participants

Participants

During the 4-day (Days 0-3) post-vaccination period

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Units	Counts
Participants

Secondary

Number of Subjects With Any Solicited General AEs

Assessed solicited general AEs were drowsiness, irritability/fussiness and loss of appetite. Any = Occurrence of AE regardless of intensity grade or relation to vaccination.

Analysis was performed on TVC which included all vaccinated subjects with administration of either Priorix or M-M-R II/M-M-R VaxPro lots documented.

Posted

Count of Participants

Participants

During the 15-day (Days 0-14) post-vaccination period

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Units	Counts
Participants

Secondary

Number of Subjects Reporting Any Fever

Any fever (≥ 38°C) = Occurrence of fever regardless of intensity grade or relation to vaccination.

Analysis was performed on TVC which included all vaccinated subjects with administration of either Priorix or M-M-R II/M-M-R VaxPro lots documented.

Posted

Count of Participants

Participants

During the 43-day (Days 0-42) post-vaccination period

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Units	Counts
Participants	OG000

Secondary

Number of Subjects Reporting Any Rash

Any rash = Occurrence of AE regardless of intensity grade or relation to vaccination.

Analysis was performed on TVC which included all vaccinated subjects with administration of either Priorix or M-M-R II/M-M-R VaxPro lots documented.

Posted

Count of Participants

Participants

During the 43-day (Days 0-42) post-vaccination period

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Units	Counts
Participants	OG000

Secondary

Number of Subjects Reporting MMR Specific Solicited General AEs

Assessed MMR specific solicited general AEs were parotid gland swelling and any suspected signs of meningism including febrile convulsions. Any = Occurrence of AE regardless of intensity grade or relation to vaccination.

Analysis was performed on TVC which included all vaccinated subjects with administration of either Priorix or M-M-R II/M-M-R VaxPro lots documented.

Posted

Count of Participants

Participants

During the 43-day (Days 0-42) post-vaccination period

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Units	Counts
Participants

Secondary

Number of Subjects Reporting Any Unsolicited AEs

Unsolicited AE included any AE reported in addition to those solicited during the clinical study and any 'solicited' AE with onset outside the specified period of follow-up for solicited AEs. Any = Occurrence of AE regardless of intensity grade or relation to vaccination.

Analysis was performed on TVC which included all vaccinated subjects with administration of either Priorix or M-M-R II/M-M-R VaxPro lots documented.

Posted

Count of Participants

Participants

During the 43-day (Days 0-42) post-vaccination period

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Units	Counts
Participants

Secondary

Number of Subjects Reporting AEs of Specific Interest

AEs of specific interest included new onset chronic disease (NOCD) (e.g., autoimmune disorders, asthma, type I diabetes, vasculitis, celiac disease, conditions associated with sub-acute or chronic thrombocytopenia and allergies) and AEs prompting emergency room (ER) visits.

Analysis was performed on TVC which included all vaccinated subjects with administration of either Priorix or M-M-R II/M-M-R VaxPro lots documented.

Posted

Count of Participants

Participants

Day 0 through the end of the study (Day 180)

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Units	Counts
Participants

Secondary

Number of Subjects Reporting Any Serious Adverse Events (SAEs)

SAE included any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity. Any = Occurrence of AE regardless of intensity grade or relation to vaccination.

Analysis was performed on TVC which included all vaccinated subjects with administration of either Priorix or M-M-R II/M-M-R VaxPro lots documented.

Posted

Count of Participants

Participants

Day 0 through the end of the study (Day 180)

ID	Title	Description
OG000	INV_MMR	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Units	Counts
Participants

Secondary

Number of Subjects Reporting Measles-like Illness

Measles-like illness was defined as the occurrence of the following signs/symptoms in the absence of another confirmed diagnosis:

maculopapular rash (includes measles/rubella-like rash), fever (≥ 38°C) and at least one of the symptoms: cough, coryza (runny nose), conjunctivitis or diarrhea, with fever or rash. Other event must be one of cough, coryza, conjunctivitis, or diarrhea.

Analysis was performed on TVC which included all vaccinated subjects with administration of either Priorix or M-M-R II/M-M-R VaxPro lots documented.

Posted

Count of Participants

Participants

During Day 5 to Day 12 post-vaccination period

ID	Title	Description
OG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
OG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.

Units	Counts

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Immune thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected1,164 at risk EG0011 events1 affected572 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Gastritis	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected1,164 at risk EG0011 events1 affected572 at risk
Acute sinusitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Bacterial infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected1,164 at risk EG0011 events1 affected572 at risk
Bronchiolitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0011 events1 affected572 at risk
Bronchitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0002 events1 affected1,164 at risk EG0013 events2 affected572 at risk
Cellulitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Croup infectious	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Exanthema subitum	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Fungal skin infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected1,164 at risk EG0011 events1 affected572 at risk
Gastroenteritis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Gastroenteritis norovirus	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Gastroenteritis salmonella	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Hand-foot-and-mouth disease	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Influenza	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected1,164 at risk EG0011 events1 affected572 at risk
Laryngitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Otitis media	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Parainfluenzae virus infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Periorbital cellulitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Pneumonia	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0004 events4 affected1,164 at risk EG0011 events1 affected572 at risk
Pneumonia respiratory syncytial viral	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Respiratory syncytial virus infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Salmonellosis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Staphylococcal infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Tonsillitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0003 events3 affected1,164 at risk EG0010 events0 affected572 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Febrile convulsion	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Lethargy	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Seizure	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Bronchial hyperreactivity	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected1,164 at risk EG0011 events1 affected572 at risk
Obstructive airways disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0010 events0 affected572 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected1,164 at risk EG0011 events1 affected572 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG000105 events95 affected1,164 at risk EG00153 events46 affected572 at risk
Teething	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00071 events59 affected1,164 at risk EG00117 events15 affected572 at risk
Injection site erythema	General disorders	MedDRA 19.0	Systematic Assessment	EG000297 events284 affected1,164 at risk EG001149 events143 affected572 at risk
Injection site pain	General disorders	MedDRA 19.0	Systematic Assessment	EG000314 events313 affected1,164 at risk EG001133 events133 affected572 at risk
Injection site swelling	General disorders	MedDRA 19.0	Systematic Assessment	EG000108 events105 affected1,164 at risk EG00162 events61 affected572 at risk
Pyrexia	General disorders	MedDRA 19.0	Systematic Assessment	EG000350 events350 affected1,164 at risk EG001180 events180 affected572 at risk
Otitis media	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG00095 events86 affected1,164 at risk EG00136 events35 affected572 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG000119 events111 affected1,164 at risk EG00175 events73 affected572 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG000497 events495 affected1,164 at risk EG001234 events233 affected572 at risk
Somnolence	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG000529 events529 affected1,164 at risk EG001238 events238 affected572 at risk
Irritability	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG000740 events723 affected1,164 at risk EG001350 events348 affected572 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG00085 events80 affected1,164 at risk EG00131 events30 affected572 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG000275 events275 affected1,164 at risk EG001152 events152 affected572 at risk

ID	Term
D008457	Measles
D009107	Mumps
D012409	Rubella

ID	Term
D018185	Morbillivirus Infections
D018184	Paramyxoviridae Infections
D018701	Mononegavirales Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D007239	Infections
D019351	Rubulavirus Infections
D010309	Parotitis
D010305	Parotid Diseases
D012466	Salivary Gland Diseases
D009059	Mouth Diseases
D009057	Stomatognathic Diseases
D018355	Rubivirus Infections
D014036	Togaviridae Infections

ID	Term
D022542	Measles-Mumps-Rubella Vaccine
D014612	Vaccines
D019433	Chickenpox Vaccine
D022362	Hepatitis A Vaccines
C538862	13-valent pneumococcal vaccine
C028581	CRM197 (non-toxic variant of diphtheria toxin)

ID	Term
D017778	Vaccines, Combined
D001688	Biological Products
D045424	Complex Mixtures
D008458	Measles Vaccine
D014765	Viral Vaccines
D009108	Mumps Vaccine
D012411	Rubella Vaccine
D022283	Herpesvirus Vaccines
D014761	Viral Hepatitis Vaccines

ID	Title	Description
BG000	INV_MMR	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
BG001	COM_MMR	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	INV_MMR Group	Subjects received 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.	0	1,164	24	1,164	980	1,164
EG001	COM_MMR Group	Subjects received 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also received Prevnar 13 at Day 0.	0	572	9	572	477	572