A Study on the Immune Response and Safety of an Investigational Combined Measles, Mumps, Rubella and Varicella Vaccine, When Given to Healthy Children 4 to 6 Years of Age

• MMRVNS vaccine (Biological): MMRVNS vaccine will be administered on Day 1.
• MMRV vaccine (Biological), also known as ProQuad: MMRV vaccine will be administered on Day 1.
• DTaP-IPV vaccine (Biological), also known as Kinrix: DTaP-IPV vaccine will be administered on Day 1.

Primary outcomes

• Geometric mean concentrations (GMCs) of immunoglobulin G (IgG) antibodies against measles, mumps, rubella, and varicella zoster virus (VZV) glycoprotein E (gE) after MMRVNS vaccine administration [At Day 43]: This outcome measure evaluates immunological consistency.
• Number of participants with seroresponse against measles, mumps, rubella, and VZV gE after MMRVNS or MMRV administration [At Day 43]: This outcome measure evaluates immunological non-inferiority. Seroresponse is defined as post-vaccination IgG antibody concentrations equal to or above threshold values as follows: The seroresponse of a participant is: * zero (non-seroresponder) if the IgG concentration is below the seroresponse threshold of the assay, * One (seroresponder) if the IgG concentration is above or equal to the seroresponse threshold.
• GMCs of IgG concentrations against measles, mumps, rubella, and VZV gE after MMRVNS or MMRV administration [At Day 43]: This outcome measure evaluates immunological non-inferiority.

Secondary outcomes

• GMCs of IgG antibodies against diphtheria, tetanus, and pertussis antigens (Bordetella pertussis toxin, filamentous hemagglutinin, and outer membrane protein pertactin) after MMRVNS or MMRV administration in a subset of participants [At Day 43]: This outcome measure evaluates immunological non-inferiority.
• Geometric mean titers (GMTs) of neutralizing antibodies against poliovirus 1, 2, and 3 after MMRVNS or MMRV administration in a subset of participants [At Day 43]: This outcome measure evaluates immunological non-inferiority.
• Booster response of IgG concentrations against pertussis antigens (Bordetella pertussis toxin, filamentous hemagglutinin, and outer membrane pertactin) after DTaP-IPV co-administration with MMRVNS or MMRV in a subset of participants [At Day 43]: The booster response of a participant is: One (responder) if: \- the pre-vaccination antibody concentration is below the assay cut-off, and the post-vaccination antibody concentration is >=4 times the assay cut-off. or, - the pre-vaccination antibody concentration is between the assay cut-off and 4 times the assay cut-off, and the post-vaccination antibody concentration is >=4 times the pre vaccination antibody concentration. or, \- the pre-vaccination antibody concentration is greater or equal to 4 times the assay cut-off, and the post vaccination antibody concentration is >=2 times the pre-vaccination antibody concentration. Zero (non-responder) in all other cases.
• Number of participants with any solicited administration site events following MMRVNS or MMRV administration [From Day 1 to Day 4 for injection site redness, pain/tenderness, and swelling; and from Day 1 to Day 43 for injection site varicella-like rash]: Solicited administration site events are injection site redness, pain/tenderness, swelling, and injection site varicella-like rash.
• Number of participants with any solicited systemic events following MMRVNS or MMRV administration [From Day 1 to Day 15 for somnolence and loss of appetite; Day 1 to Day 22 for fever; Day 1 to Day 43 for varicella-like rash (non-injection site), measles/rubella-like rash, and other rash]: Solicited systemic events are somnolence (sleepiness/drowsiness), loss of appetite, fever, varicella-like rash (non-injection site), measles/rubella-like rash, and other rash that is not varicella-like or measles/rubella-like rash.
• Number of participants with any unsolicited adverse events (AEs) following MMRVNS or MMRV administration [From Day 1 to Day 43]: An unsolicited AE is an AE that is either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow- up for solicited events.
• Number of participants with any medically attended adverse events (MAAEs) following MMRVNS or MMRV administration [From Day 1 to Day 181]: MAAEs are solicited AEs and unsolicited nonserious AEs for which the participant received medical attention (an unscheduled visit to or from medical personnel for any reason, including emergency room visits).
• Number of participants with serious adverse events (SAEs), fatal SAEs, and related SAEs following MMRVNS or MMRV administration [From Day 1 to Day 181]: An SAE is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, or other medically significant events.

Sex: All, ages: 4 Years to 6 Years, accepts healthy volunteers

Inclusion Criteria (INC):

* INC#1 Participant's parent(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 eDiaries, return for follow-up visits).
* INC#2 Written or witnessed/thumb printed or digital informed consent obtained from the participant's parent(s)/LAR(s) prior to performance of any study specific procedure.
* INC#3 Informed assent obtained from the participants in line with local rules and regulations.
* INC#4 Healthy participants as established by medical history and clinical examination at screening.
* INC#5 A male or female participant between and including 4 and 6 years of age (i.e., from fourth birthday until the day before the seventh birthday) at the time of the study interventions administration, and in accordance with local regulations.
* INC#6 Participant who previously received a first dose of varicella-containing vaccine in the second year of life (i.e., from first birthday at 12 months of age until the day before the second birthday at 24 months of age).
* INC#7 Participant who previously received a first dose of measles, mumps, rubella containing vaccine in the second year of life (i.e., from first birthday at 12 months of age until the day before the second birthday at 24 months of age).
* INC#8 Participant who previously received 3 or 4 doses of any combined DTP (DTaP/DTwP) vaccine (diphtheria and tetanus toxoids and pertussis antigens whether or not combined with hepatitis B, inactivated poliovirus or Haemophilus influenzae type b antigens) according to the local recommendations.

Exclusion Criteria (EXC):

* EXC#1 History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions, including hypersensitivity to neomycin or gelatin.
* EXC#2 Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
* EXC#3 Hypersensitivity to latex.
* EXC#4 Unstable chronic conditions as determined by medical history and physical examination.
* EXC#5 Major congenital defects, as assessed by the investigator.
* EXC#6 History of measles, mumps, rubella or varicella/zoster disease as evaluated by the investigator.
* EXC#7 History of diphtheria, tetanus, pertussis, and/or poliomyelitis disease.
* EXC#8 Recurrent history or uncontrolled neurological disorders or any neuroinflammatory (including, but not limited to: demyelinating disorders, encephalitis or myelitis of any origin), congenital neurological conditions, encephalopathies, or seizures (including all subtypes, such as: absence seizures, generalized tonic-clonic seizures, partial complex seizures, partial simple seizures).
* EXC#9 Active untreated tuberculosis.
* EXC#10 Condition that, in the judgment of the investigator, would make intramuscular injection unsafe.
* EXC#11 Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the clinical study.
* EXC#12 Use of any investigational or non-registered product (drug, vaccine, or invasive medical device in the country of enrollment) other than the study interventions during the period beginning 30 days before the dose of study interventions (Day -29 to Day 1), or their planned use during the study period.
* EXC#13 Administration of immunoglobulins or other blood products or plasma derivatives during the period starting 90 days before the study intervention or planned administration during the study period.
* EXC#14 Chronic administration of immune-modifying drugs (defined as more than 14 consecutive days in total) and/or planned use of long-acting immune modifying treatments at any time up to the end of the study.

  * Up to 90 days prior to the study interventions administration.

    * For corticosteroids, this will mean prednisone equivalent ≥0.5 mg/kg/day with maximum of 20 mg/day for pediatric participants. Inhaled, intra-articular/intra-bursal and topical steroids are allowed.
  * Up to 180 days prior to study interventions administration: long-acting immune-modifying drugs including among others immunotherapy (e.g., tumor necrosis factor-inhibitors), monoclonal antibodies (except the ones not interfering with the immune response to the study interventions, e.g., nirsevimab), antitumoral medication.
* EXC#15 Previous vaccination with a second dose of varicella-containing vaccine or measles, mumps, rubella containing vaccine.
* EXC#16 Vaccination against diphtheria, tetanus, pertussis, and/or poliomyelitis given after the second year of life (i.e., after the second birthday at 24 months of age).
* EXC#17 Occurrence of any of the following events after a previous administration of DTP vaccine:

  * Encephalopathy of unknown etiology occurring during the period starting within 7 days of vaccination of a previous administration of DTP vaccine.
  * A temperature (≥40.6°C \[≥105°F\]) during the period starting 48 hours after vaccination not due to another identifiable cause.
* EXC#18 Use of salicylates (aspirin) or salicylate-containing products or its planned use, during the period of 6 weeks following study interventions administration.
* EXC#19 Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the dose and ending 43 days after the dose of study interventions administration* (Visit 2), with the exception of

Influenza vaccines:

* Inactivated influenza vaccine must not be administered in the period starting 28 days before the dose and ending 28 days after the dose of study intervention administration. If administered outside this prohibited period, it should be administered at a different location than the study intervention.
* Live attenuated influenza vaccine must not be administered during the period starting 30 days before the dose and ending 43 days after the dose of study intervention administration (Visit 2).

  * If emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) is recommended and/or organized by public health authorities outside the routine immunization program, the time period described above can be reduced, provided it is used according to the local governmental recommendations and sponsor is notified.

    * EXC#20 Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (drug/vaccine/invasive medical device).
    * EXC#21 Any study personnel's immediate dependents, family, or household members.
    * EXC#22 Child in care.
    * EXC#23 Participants with the following high-risk individuals in their household:

      * Immunocompromised individuals.
      * Pregnant women without documented history of varicella.
      * Newborn infants of mothers without documented history of varicella.
      * Newborn infants born <28 weeks of gestation.

NIH grants: 2025