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

A Phase II, Single-blind, Randomized, Controlled Study to Evaluate the Immunogenicity and Safety of a Measles, Mumps, Rubella, Varicella Vaccine Compared With ProQuad, Administered in Healthy Children 4-6 Years of Age

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.

Study Overview

• Status: Recruiting
• Conditions: Measles; Mumps; Rubella; Chickenpox
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Anticipated): 800
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Kevin G Rouse
  • Florida
    • Tampa, Florida, United States, 33613
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Teena L. Hughes
  • Kentucky
    • Louisville, Kentucky, United States, 40291
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: John B Blair
  • Nebraska
    • Lincoln, Nebraska, United States, 68505
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Sue A Springman
  • Ohio
    • Dayton, Ohio, United States, 45414
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Julie S Shepard
  • Tennessee
    • Tullahoma, Tennessee, United States, 37388
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Clifford Seyler
  • Utah
    • Layton, Utah, United States, 84041
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Colton Ragsdale
    • Provo, Utah, United States, 84604
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Joshua Fuller
    • Roy, Utah, United States, 84067
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Daniel B Neumann
    • South Jordan, Utah, United States, 84095
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Mary D Tipton

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 6 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MMRV(H)NS Group; Healthy children aged 4 to 6 years of age receive 1 dose of an investigational measles, mumps, and rubella (MMR) at release potency and varicella at high (V[H]NS) potency vaccine on Day 1.	Biological: Investigational MMRV(H)NS vaccine; 1 dose of a measles, mumps, and rubella at release potency and VNS at high (H) potency vaccine administered subcutaneously.
Experimental: MM(H)RVNS Group; Healthy children aged 4 to 6 years of age receive 1 dose of an investigational measles, rubella (MR), and varicella (VNS) at release potency and mumps at high (M[H]) potency vaccine on Day 1.	Biological: Investigational MM(H)RVNS vaccine; 1 dose of a measles, rubella, and varicella at release potency and mumps at high (H) potency vaccine administered subcutaneously.
Experimental: M(L)M(L)R(L)V(L)NS Group; Healthy children aged 4 to 6 years of age receive 1 dose of an investigational measles, mumps, rubella (MMR), and varicella (VNS), all at low (L) potency vaccine on Day 1.	Biological: Investigational M(L)M(L)R(L)V(L)NS vaccine; 1 dose of measles, mumps, rubella, and varicella, all at low (L) potency vaccine administered subcutaneously.
Active Comparator: MMRV_Lot 1 and Lot 2 Pooled Group; Healthy children aged 4 to 6 years of age receive 1 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.	Biological: Marketed MMRV_Lot 1 and Lot 2 vaccine; 1 dose of a marketed measles, mumps, rubella, and varicella of Lot 1 or 1 dose of a marketed measles, mumps, rubella, and varicella of Lot 2 vaccine administered subcutaneously.; Other Names: ProQuad

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-measles antibody geometric mean concentrations (GMCs)	Antibody GMCs will be summarized for measles antigen by treatment group with their 2-sided 95% confidence interval (CI), minimum and maximum, derived considering log-transformed concentrations are normally distributed with unknown variance for antibodies against measles antigen. Antibody concentrations will be presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL).	At Day 43
Anti-mumps antibody GMCs	Antibody GMCs will be summarized for mumps antigen by treatment group with their 2-sided 95% confidence interval (CI), minimum and maximum, derived considering log-transformed concentrations are normally distributed with unknown variance for antibodies against mumps antigen. Antibody concentrations will be presented as GMCs, expressed in Arbitrary unit per milliliter (AU/mL).	At Day 43
Anti-rubella antibody GMCs	Antibody GMCs will be summarized for rubella antigen by treatment group with their 2-sided 95% confidence interval (CI), minimum and maximum, derived considering log-transformed concentrations are normally distributed with unknown variance for antibodies against rubella antigen. Antibody concentrations will be presented as GMCs, expressed in International unit per milliliter (IU/mL).	At Day 43
Anti-glycoprotein E (gE) antibody GMCs	Antibody GMCs will be summarized for varicella antigen by treatment group with their 2-sided 95% confidence interval (CI), minimum and maximum, derived considering log-transformed concentrations are normally distributed with unknown variance for antibodies against varicella antigen. Anti gE antibody concentrations will be presented as GMCs, expressed in mIU/mL	At Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with seroresponse to anti-measles antibodies	Seroresponse rate for measles is defined as the percentage of participants for whom the post-dose antibody concentration as measured by the anti-measles Multiplex Luminex based Immuno assay is greater than or equal to (>=) 67 mIU/mL for each group.	Day 43
Percentage of participants with seroresponse to anti-mumps antibodies	Seroresponse rate for mumps is defined as the percentage of participants for whom the post-dose antibody concentration as measured by the anti-mumps Multiplex Luminex based Immuno assay is >= 296 AU/mL for each group.	Day 43
Percentage of participants with seroresponse to anti-rubella antibodies	Seroresponse rate for rubella is defined as the percentage of participants for whom the post-dose antibody concentration as measured by the anti-rubella Multiplex Luminex based Immuno assay is >= 17 IU/mL for each group.	Day 43
Percentage of participants with seroresponse to varicella anti-gE antibodies	Seroresponse rate for varicella is defined as the percentage of participants for whom the post-dose anti-gE antibody concentration is >= 300 mIU/mL for each group.	Day 43
Percentage of participants reporting each solicited administration site event	Solicited administration site events include injection site redness, pain and swelling.	During the 4-day period (day of administration and 3 following days) after the administration of study interventions (administered at Day 1)
Percentage of participants reporting each solicited systemic event in terms of drowsiness and loss of appetite	Solicited systemic events include drowsiness, loss of appetite, after the administration of study intervention for each group.	During the 4-day (day of administration and 3 following days) period after the administration of study interventions (administered at Day 1)
Percentage of participants reporting each solicited systemic event in terms of fever, measles/rubella-like rash, varicella-like rash and other rash (not measles/rubella-like rash or varicella-like rash)	Solicited systemic events include fever, measles/rubella-like rash, or varicella like rash, and other rash (not measles/rubella-like rash or varicella-like rash) after the administration of study interventions for each group. Fever is defined as temperature greater than or equal to (>=)38.0 degrees Celsius (°C) (100.4 degrees Fahrenheit [°F]) by any route (the preferred location for measuring temperature is the axilla).	During the 43-day period (day of administration and 42 following days) after the administration of study interventions (administered at Day 1)
Percentage of participants reporting unsolicited adverse events (AEs)	Unsolicited AEs include any AE reported in addition to solicited events during the study, or any "solicited" symptoms with onset outside of the specified period of follow-up for solicited symptoms, are assessed for each group after the administration of all vaccines.	During the 43-day (day of administration and 42 following days) period after the administration of study interventions (administered at Day 1)
Percentage of participants reporting serious adverse events (SAEs)	A SAE is an AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or other situations that are considered serious per medical or scientific judgment.	Throughout the entire study period (From Day 1 to Day 181)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2022
• Primary Completion (Anticipated): January 31, 2024
• Study Completion (Anticipated): June 17, 2024

Study Registration Dates

• First Submitted: November 24, 2022
• First Submitted That Met QC Criteria: November 24, 2022
• First Posted (Actual): November 30, 2022

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 16, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Measles; Varicella; Mumps; Rubella
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Stomatognathic Diseases; Mouth Diseases; DNA Virus Infections; Morbillivirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Salivary Gland Diseases; Togaviridae Infections; Rubivirus Infections; Rubulavirus Infections; Parotitis; Parotid Diseases; Measles; Chickenpox; Rubella; Mumps; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 217715; 2022-501564-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No