A Study on the Immune Response and Safety of a Combined Measles, Mumps, Rubella, Chickenpox Vaccine Compared to a Marketed Combined Vaccine, Given to Healthy Children 4 to 6 Years of Age

Phase 2

Completed

Conditions: Measles; Mumps; Rubella; Chickenpox
Measles

Interventions: Biological: Investigational MMRV(H)NS vaccine
Biological: Investigational MM(H)RVNS vaccine
Biological: Investigational M(L)M(L)R(L)V(L)NS vaccine
Biological: Marketed MMRV_Lot 1 and Lot 2 vaccine

Registration Number: NCT05630846

Lead Sponsor: GlaxoSmithKline

Brief Summary: The main purpose of this study is to assess immune response and safety of various potencies of a measles, mumps, rubella, and varicella (MMRVNS) vaccines given to healthy children of 4 to 6 years of age.

Detailed Description: This study is designed to evaluate the immunogenicity and safety of the investigational measles, mumps, rubella, varicella vaccine (referred to as the MMRVNS vaccine) compared with the licensed measles, mumps, rubella, varicella vaccine, ProQuad (referred to as the MMRV vaccine), when given as a second dose to children 4 to 6 years of age who were previously primed with a first dose of any combination of measles, mumps, rubella, and varicella-containing vaccine(s).

This study will evaluate immunogenicity and safety using 3 MMRVNS formulations which vary for some or all the individual virus potencies. The 3 MMRVNS formulations (designated as MMRV(H)NS vaccine, MM(H)RVNS vaccine and M(L)M(L)R(L)V(L)NS vaccine) will be compared with the MMRV vaccine. To ensure representative data on the comparator, participants enrolled in the MMRV group will be randomized to two different lots (designated as MMRV_Lot 1 and MMRV_Lot 2). Throughout the study, the two lots will be analyzed as a pooled group.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 801

Inclusion Criteria

Healthy participants as established by medical history and clinical examination before entering into the study.
A male or female between, and including, 4 years and 6 years of age (i.e., from 4 year birthday until the day before the 7-year birthday) at the time of study intervention administration, and in accordance with local regulations.
Participant who previously received a first dose of varicella-containing vaccine in the second year of life.
Participant who previously received a single dose of measles-, mumps-, rubella-containing vaccine in the second year of life.
Written informed consent obtained from the participants' parent(s)/legally acceptable representative(s) (LAR[s]) prior to performance of any study-specific procedure (participant informed assent will be obtained from participants in line with local rules and regulations).
Participants' 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 electronic diaries [eDiaries], return for follow-up visits).

Exclusion Criteria

Medical Conditions

History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions including hypersensitivity to neomycin or gelatin.
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
Hypersensitivity to latex.
Major congenital defects, as assessed by the investigator.
History of measles, mumps, rubella, or varicella disease.
Recurrent history of or uncontrolled neurological disorders or seizures.
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 body temperature >=38.0 degrees Celsius (°C) (100.4 degrees Fahrenheit [°F)] by any age-appropriate route. All study interventions can be administered to participants with a minor illness such as diarrhea, mild upper respiratory infection without fever.
Participant with history of coronavirus disease 2019 (COVID-19) who is still symptomatic.
Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.

Prior and Concomitant Therapy

Use of any investigational or non-registered product (drug, vaccine, or medical device) 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.
Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the study intervention administration. For corticosteroids, this will mean prednisone equivalent >= 0.5 mg/kg/day or 20 mg/day whichever is the maximum dose for pediatric participants. Inhaled and topical steroids are allowed.
Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 180 days before the dose of study interventions or planned administration during the study period.
Administration of long-acting immune-modifying drugs at any time during the study period (e.g., infliximab).
Previous vaccination with a second dose of varicella-containing vaccine or measles-, mumps-, rubella-containing vaccine.
Administration or planned administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the dose and ending at 43 days after the dose of study interventions administration* (Visit 3), with the exception of:
- inactivated influenza (flu) vaccine which may be given at any time during the study and administered at a different location than the study interventions and,
- routinely recommended licensed childhood DTPa-containing vaccines which can preferably be co-administered according to the local immunization practices of the participating country.
Any other age-appropriate vaccine may be given starting at Visit 3 and anytime thereafter.
- In case an 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 if necessary for that vaccine, provided it is used according to the local government recommendations and that GSK/IQVIA is notified accordingly.

Prior/Concurrent Clinical Study Experience

• 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/invasive medical device).

Other Exclusions

Child in care.
Any study personnel's immediate dependents, family, or household members.
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MMRV(H)NS Group	Investigational MMRV(H)NS vaccine	Participants receive a single dose of an investigational measles, mumps, and rubella (MMR) at release potency and varicella at high (V\[H\]NS) potency vaccine on Day 1.
MM(H)RVNS Group	Investigational MM(H)RVNS vaccine	Participants receive a single dose of an investigational measles, rubella (MR), and varicella (VNS) at release potency and mumps at high (M\[H\]) potency vaccine on Day 1.
M(L)M(L)R(L)V(L)NS Group	Investigational M(L)M(L)R(L)V(L)NS vaccine	Participants receive a single dose of an investigational measles, mumps, rubella (MMR), and varicella (VNS), all at low (L) potency vaccine on Day 1.
MMRV_Lot 1 and Lot 2 Pooled Group	Marketed MMRV_Lot 1 and Lot 2 vaccine	Participants receive a single dose of a marketed measles, mumps, rubella (MMR), and varicella (V) vaccine of Lot 1 or of 1 vaccine dose of a marketed MMRV vaccine of Lot 2 on Day 1.

Primary Outcome Measures

Name	Time	Method
GMC of Anti-measles Antibodies at Day 43	At Day 43	Anti-measles antibodies were measured with multiplex luminex based immuno assay and the results were expressed as GMC, in milli international units per milliliter (mIU/mL). Analysis was performed on per protocol set which included all eligible participants who received study intervention as per protocol, were not unblinded, had immunogenicity results pre- and post-dose for at least 1 antigen, complied with blood draw interval between study intervention and post- dose blood sample, without intercurrent medical conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination. Only participants with data available at specified timepoint were included in the analysis.
GMC of Anti-mumps Antibodies at Day 43	At Day 43	Anti-mumps antibodies were measured with multiplex luminex based immuno assay and the results were expressed as GMC, in arbitrary units per milliliter (AU/mL). Analysis was performed on per protocol set. Only participants with data available at specified timepoint were included in the analysis.
GMC of Anti-rubella Antibodies at Day 43	At Day 43	Anti-rubella antibodies were measured with multiplex luminex based immuno assay and the results were expressed as GMC, in international units per milliliter (IU/mL). Analysis was performed on per protocol set. Only participants with data available at specified timepoint were included in the analysis.
GMC of Anti-glycoprotein E (gE) Antibodies at Day 43	At Day 43	Anti-gE antibodies were measured with enzyme linked immunosorbent assay and the results were expressed as GMC, in mIU/mL. Anti-varicella and anti-varicella zoster virus gE were used interchangeably. Analysis was performed on per protocol set. Only participants with data available at specified timepoint were included in the analysis.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Seroresponse for Measles Antibodies at Day 43	At Day 43	Seroresponse was defined as the participants of participants for whom the Day 43 measles antibodies concentration was \>=116 mIU/mL. Analysis was performed on per protocol set. Only participants with data available at specified timepoint were included in the analysis.
Percentage of Participants With Seroresponse for Mumps Antibodies at Day 43	At Day 43	Seroresponse was defined as the participants of participants for whom the Day 43 mumps antibodies concentration was \>=296 AU/mL. Analysis was performed on per protocol set. Only participants with data available at specified timepoint were included in the analysis.
Percentage of Participants With Seroresponse for Rubella Antibodies at Day 43	At Day 43	Seroresponse was defined as the participants of participants for whom the Day 43 rubella antibodies concentration was \>=24 IU/mL. Analysis was performed on per protocol set. Only participants with data available at specified timepoint were included in the analysis.
Percentage of Participants With Seroresponse for Varicella Antibodies at Day 43	At Day 43	Seroresponse was defined as the participants of participants for whom the Day 43 varicella antibodies concentration was \>=300 mIU/mL. Analysis was performed on per protocol set. Only participants with data available at specified timepoint were included in the analysis.
Number of Participants With Solicited Administration Site Adverse Events (AEs) During the 4-day Period After Vaccine Dose Administration	Day 1 to Day 4	The solicited administration site events after vaccination included pain, erythema/redness, and swelling. Analysis was performed on exposed set which included all participants who received a study intervention. Only those participants with solicited AEs were included in this analysis.
Number of Participants With Solicited Systemic AEs During the 4-day Period After Vaccine Dose Administration	Day 1 to Day 4	The solicited systemic events after vaccination included drowsiness and loss of appetite. Analysis was performed on exposed set. Only those participants with solicited AEs were included in this analysis.
Number of Participants With Solicited Systemic AEs During the 43-day Period After Vaccine Dose Administration	Day 1 to Day 43	The solicited systemic events after vaccination included fever, measles/rubella-like rash, varicella- like rash and other rash (not measles/rubella-like rash or varicella-like rash). Fever was defined as temperature greater than or equal to 38.0 degrees Celsius (100.4 degrees Fahrenheit) by any route (the preferred location for measuring temperature is the axilla). Analysis was performed on exposed set. Only those participants with solicited AEs were included in this analysis.
Number of Participants With Unsolicited AEs During the 43-day Period After Vaccine Dose Administration	Day 1 to Day 43	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study vaccine, which does not necessarily have a causal relationship with study vaccine. An unsolicited AE was an AE that was either not included in the list of solicited events or was included in the list of solicited events but with an onset outside the specified period of follow- up for solicited events. Unsolicited AEs must have been communicated by participant/participant's caregiver(s) who had signed the informed consent. Unsolicited AEs included both serious adverse events (SAEs) and non-serious AEs. Analysis was performed on exposed set.
Number of Participants With SAEs After Vaccine Dose Administration	Throughout the study period (Day 1 to Day 181)	An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in congenital anomaly or other significant medical events. Analysis was performed on exposed set.