Measles, mumps and rubella

Co-Primary ! To demonstrate the safety profile (fever >39.0°C (>102.2°F)) of Inv_MMR compared to Com_MMR (pooled lots) when coadministered with VV and HAV (to all children) and PCV-13 (only to children enrolled in the US). ! For the Inv_MMR vaccine as compared to the Com_MMR vaccine, the upper limit of the 2-sided standardized asymptotic 95% CI for the group difference (Inv_MMR minus Com_MMR) in incidence of fever >39.0°C (>102.2°F) within 5-12 days post-vaccination is equal to or below 5%. ! To demonstrate the safety profile (fever ≥38.0°C (≥100.4°F)) of Inv_MMR compared to Com_MMR (pooled lots) when co- administered with VV and HAV (to all children) and PCV-13 (children enrolled in the US). Criteria: ! For the Inv_MMR vaccine as compared to the Com_MMR vaccine, the upper limit of the 2-sided standardized asymptotic 95% CI for the group difference (Inv_MMR minus Com_MMR) in incidence of fever ≥38.0°C (≥100.4°F) within 5-12 days post-vaccination is equal to or below 10%.

Measles, mumps and rubella (MMR) vaccine live

Live attenuated measles virus
Live attenuated Mumps virus
Live attenuated rubella virus

Lyophilized pellet in a vial

10
10
10

Co-Primary
! Assessment of fever after MMR vaccination.
! Occurrence of fever > 39.0°C (>102.2°F) from Day 5
through Day 12
! Occurrence of fever ≥ 38.0°C (≥100.4°F) from Day 5
through Day 12.
Secondary
! Immunogenicity of the MMR vaccines at Day 42.
! Seroresponse to measles, mumps and rubella viruses.
! Measles, mumps and rubella virus antibody concentrations.
! Solicited local and general symptoms.
! Occurrence of solicited local symptoms in terms of
injection site redness, pain and swelling from Day 0 to Day
3 after vaccination.
! Occurrence of solicited general symptoms in terms of
drowsiness, loss of appetite and irritability from Day 0 to
Day 14 after vaccination.
! Occurrence of solicited general symptoms in terms of fever
(temperature ≥38.0°C / 100.4°F), rash, parotid/salivary
gland swelling, any sign of meningism (including febrile
convulsions) from Day 0 to Day 42 after vaccination.
! Unsolicited adverse events.
! Occurrence of unsolicited symptoms, according to the
Medical Dictionary for Regulatory Activities (MedDRA)
classification, from Day 0 to Day 42 after vaccination.
! Adverse events of specific interest.
! Occurrence of 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 from Day 0 through
the end of study.
! Serious adverse events.
! Occurrence of serious adverse events from Day 0 through
the end of study.
! Measles-like illness
! Occurrence of any measles-like illness from Day 5 through
Day 12 post vaccination
Measles-like illness is defined as the occurrence of the
following signs/symptoms in the absence of another confirmed
diagnosis (e.g. laboratory confirmed scarlet fever):
(1) temperature ≥38°C/100.4°F
AND
(2) maculopapular rash*
AND at least one of the following signs/symptoms
(3) cough, coryza (runny nose), conjunctivitis or diarrhea
with fever or rash occurring during the period of Day 5 through
Day 12 post vaccination.

Inclusion criteria for enrollment
Deviations from inclusion criteria are not allowed because they can potentially
jeopardize the scientific integrity of the study, regulatory acceptability or subject
safety. Therefore, adherence to the criteria as specified in the protocol is essential.
All subjects must satisfy ALL the following criteria at study entry:
 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 (e.g., completion of the diary cards, return for follow-up visits, respects
intervals between visits).
 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 for enrollment
Deviations from exclusion criteria are not allowed because they can potentially
jeopardize the scientific integrity of the study, regulatory acceptability or subject
safety. Therefore, adherence to the criteria as specified in the protocol is essential.
The following criteria should be checked at the time of study entry. If ANY
exclusion criterion applies, the subject must not be included in the study:
 Child in care (refer to the GLOSSARY OF TERMS for the definition of 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.
A list of criteria that may eliminate children from ATP analyses can be found in Sections
6.7.1, 6.8 and 10.4.