A Study on the Immune Response and Safety of Various Potencies of an Investigational Chickenpox Vaccine Compared With a Marketed Chickenpox Vaccine, Given to Healthy Children 12 to 15 Months of Age

Study Overview
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Brief Summary
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The purpose of this study is to assess immune response and safety of various potencies of an investigational chickenpox vaccine given to healthy children 12 to 15 months of age.

Official Title
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A Phase II, Observer-blind, Randomized, Controlled Study to Evaluate the Immunogenicity and Safety of a Varicella Vaccine at Various Potencies Compared With Varivax, as a First Dose, Administered in Healthy Children in Their Second Year of Life

Conditions
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Chickenpox

Intervention / Treatment
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* Biological: Investigational varicella vaccine low potency
* Biological: Investigational varicella vaccine medium potency
* Biological: Investigational varicella vaccine high potency
* Biological: Marketed varicella vaccine Lot 1
* Biological: Marketed varicella vaccine Lot 2
* Biological: Measles, mumps, and rubella vaccine
* Biological: Hepatitis A vaccine
* Biological: 13-valent pneumococcal conjugate vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants as established by medical history and clinical examination before entering into the study. A male or female between, and including, 12 and 15 months of age (i.e., from his/her 1 year birthday until the day before age of 16 months) at the time of the administration of the study interventions. Written informed consent obtained from the parent(s)/legally authorized representative(s) of the participant prior to performance of any study-specific procedure. Participants' parent(s)/legally authorized representative(s), who, in the opinion of the investigator, can and will comply, with the requirements of the protocol (e.g., completion of Electronic Diaries, return for follow-up visits). Only for US participants and participants in countries where pneumococcal conjugate vaccine is recommended at 12-15 months of life as per national immunization schedule: Participants who previously received the primary series of pneumococcal conjugate vaccine in their first year of life with the last dose at least 60 days prior to study entry. 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 varicella. Recurrent history of or uncontrolled neurological disorders or seizures. Participant with history of SARS-CoV-2 infection 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 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 interventions 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, or equivalent. 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 against measles, mumps, rubella, hepatitis A, and/or varicella virus. 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 varicella. Recurrent history of or uncontrolled neurological disorders or seizures. Participant with history of SARS-CoV-2 infection 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 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 interventions 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, or equivalent. 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 against measles, mumps, rubella, hepatitis A, and/or varicella virus. Previous administration of a booster dose of any pneumococcal conjugate vaccine. Planned administration/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. Any other age appropriate vaccine may be given starting at Visit 3 and anytime thereafter. In case of 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 governmental recommendations and that the Sponsor/designee 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.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 15 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VNS_Low Group<br>Healthy children aged 12 to 15 months of age receive 1 dose of an investigational varicella vaccine (VNS) of low potency 1 dose of a measles, mumps, and rubella vaccine, 1 dose of a hepatitis A vaccine and 1 dose of a13 valent pneumococcal conjugate vaccine on Day 1. The 13 valent pneumococcal conjugate vaccine will only be administered to participants enrolled in the US and in countries where pneumococcal conjugate vaccine is recommended at 12-15 months as per national immunization schedule. | Biological: Investigational varicella vaccine low potency<br>* 1 dose of a low-potency investigational varicella vaccine administered subcutaneously in the upper arm<br>Biological: Measles, mumps, and rubella vaccine<br>* 1 dose of a measles, mumps, and rubella vaccine administered subcutaneously in the upper arm<br>Biological: Hepatitis A vaccine<br>* 1 dose of a hepatitis A vaccine administered intramuscularly in the right anterolateral thigh<br>Biological: 13-valent pneumococcal conjugate vaccine<br>* 1 dose of a 13-valent pneumococcal conjugate vaccine administered intramuscularly in the left anterolateral thigh<br>|
| Experimental: VNS_Med Group<br>Healthy children aged 12 to 15 months of age receive 1 dose of an investigational varicella vaccine (VNS) of medium potency, 1 dose of a measles, mumps, and rubella vaccine, 1 dose of a hepatitis A vaccine, and 1 dose of a 13-valent pneumococcal conjugate vaccine on Day 1. The 13 valent pneumococcal conjugate vaccine will only be administered to participants enrolled in the US and in countries where pneumococcal conjugate vaccine is recommended at 12-15 months as per national immunization schedule. | Biological: Investigational varicella vaccine medium potency<br>* 1 dose of a medium-potency investigational varicella vaccine administered subcutaneously in the upper arm<br>Biological: Measles, mumps, and rubella vaccine<br>* 1 dose of a measles, mumps, and rubella vaccine administered subcutaneously in the upper arm<br>Biological: Hepatitis A vaccine<br>* 1 dose of a hepatitis A vaccine administered intramuscularly in the right anterolateral thigh<br>Biological: 13-valent pneumococcal conjugate vaccine<br>* 1 dose of a 13-valent pneumococcal conjugate vaccine administered intramuscularly in the left anterolateral thigh<br>|
| Experimental: VNS_High Group<br>Healthy children aged 12 to 15 months of age receive 1 dose of an investigational varicella vaccine (VNS) of high potency 1 dose of a measles, mumps, and rubella vaccine, 1 dose of a hepatitis A vaccine, and 1 dose a 13-valent pneumococcal conjugate vaccine on Day 1. The 13 valent pneumococcal conjugate vaccine will only be administered to participants enrolled in the US and in countries where pneumococcal conjugate vaccine is recommended at 12-15 months as per national immunization schedule. | Biological: Investigational varicella vaccine high potency<br>* 1 dose of a high-potency investigational varicella vaccine administered subcutaneously in the upper arm<br>Biological: Measles, mumps, and rubella vaccine<br>* 1 dose of a measles, mumps, and rubella vaccine administered subcutaneously in the upper arm<br>Biological: Hepatitis A vaccine<br>* 1 dose of a hepatitis A vaccine administered intramuscularly in the right anterolateral thigh<br>Biological: 13-valent pneumococcal conjugate vaccine<br>* 1 dose of a 13-valent pneumococcal conjugate vaccine administered intramuscularly in the left anterolateral thigh<br>|
| Active Comparator: VV_Lot1 and Lot2 Pooled Group<br>Healthy children aged 12 to 15 months of age receive 1 dose of a marketed varicella vaccine (VV) of Lot 1 or 1 dose of a marketed varicella vaccine (VV) of Lot 2, 1 dose of a measles, mumps, and rubella vaccine, 1 dose of a hepatitis A vaccine, and a 1 dose of a 13-valent pneumococcal conjugate vaccine on Day 1. The 13 valent pneumococcal conjugate vaccine will only be administered to participants enrolled in the US and in countries where pneumococcal conjugate vaccine is recommended at 12-15 months as per national immunization schedule. | Biological: Marketed varicella vaccine Lot 1<br>* 1 dose of a marketed varicella vaccine of Lot 1 administered subcutaneously in the upper arm<br>Biological: Marketed varicella vaccine Lot 2<br>* 1 dose of a marketed varicella vaccine of Lot 2 administered subcutaneously in the upper arm<br>Biological: Measles, mumps, and rubella vaccine<br>* 1 dose of a measles, mumps, and rubella vaccine administered subcutaneously in the upper arm<br>Biological: Hepatitis A vaccine<br>* 1 dose of a hepatitis A vaccine administered intramuscularly in the right anterolateral thigh<br>Biological: 13-valent pneumococcal conjugate vaccine<br>* 1 dose of a 13-valent pneumococcal conjugate vaccine administered intramuscularly in the left anterolateral thigh<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of anti-varicella zoster virus (VZV) glycoprotein E (gE) antibodies | Concentrations of anti-VZV gE antibodies are presented as Geometric Mean Concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL) for each group. | At Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with seroresponse to VZV gE | Seroresponse is defined as the percentage of participants for whom the post-dose of anti VZV gE antibody concentration is greater than or equal to (≥) 300 milli-international units per milliliter (mIU/mL) for each group. | At Day 43 | 
| Percentage of participants reporting solicited administration site events | Solicited administration site events include injection site redness, pain and swelling. | During the 4-day period after the administration of study interventions (administered at Day 1) | 
| Percentage of participants reporting solicited systemic events | Solicited systemic events include fever, varicella like rash, and general rash (not varicella-like) after the administration of all vaccines 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). A typical varicella-like rash manifests as a rash/lesions that may appear within several weeks after the varicella vaccination. Lesions may contain spots, bumps, blisters, or crusts. Includes injection site varicella-like rash | During the 43-day period after the administration of study interventions (administered at Day 1) | 
| Percentage of participants reporting solicited systemic events | Solicited systemic events include drowsiness, loss of appetite, and irritability after the administration of all vaccines for each group. | During the 15-day period after the administration of study interventions (administered at Day 1) | 
| Percentage of participants reporting unsolicited adverse events | Unsolicited adverse events (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 days-period after the administration of study interventions (administrated at Day 1) | 
| Percentage of participants reporting serious adverse events (SAEs) | A SAE is an AE which 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chickenpox, Varicella