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

Phase 2

Completed

Conditions: Chickenpox

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

Registration Number: NCT05084508

Lead Sponsor: GlaxoSmithKline

Brief Summary: 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.

Detailed Description: The study aims to demonstrate the immunogenicity of the investigational VNS vaccine at three potencies (VNS_Low, VNS_Med, and VNS_High) compared to the licensed varicella vaccine, Varivax (VV), as a first dose for children aged 12 to 15 months in the US. To ensure more representative data, participants in the VV group are randomized into two lots (VV_Lot1 and VV_Lot2), which are analyzed as pooled lots throughout the study. Besides assessing immunogenicity, the study also seeks to generate safety data.

In the US, participants will receive additional vaccines: a measles, mumps, and rubella vaccine (MMR), a hepatitis A vaccine (Havrix), and a 13-valent pneumococcal conjugate vaccine (Prevnar 13). Participants outside the US will receive an MMR vaccine (M-M-R II or M-M-RVaxPro, depending on the country), Havrix, and, in some cases, Prevnar 13, but only in countries where it's recommended for children 12-15 months according to local immunization schedules.

At the end of the study, or shortly after, GSK provided re-vaccination with a dose of Varivax (VV) to participants who did not meet the pre-specified seroresponse threshold of anti-gE antibody concentration was greater than or equal to (\>=) 300 mIU/mL. Additionally, a second dose of VV and/or Havrix was offered to participants in non-US countries where local health departments do not routinely provide varicella and/or hepatitis A vaccines.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 800

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VNS_Low Group	Investigational varicella vaccine low potency	Participants received 1 dose of an investigational varicella vaccine (VNS) of low potency, 1 dose of a measles, mumps, and rubella (MMR) vaccine, 1 dose of a hepatitis A vaccine (Havrix) and 1 dose of a13 valent pneumococcal conjugate vaccine (Prevnar 13) on Day 1.
VNS_Low Group	Measles, mumps, and rubella vaccine	Participants received 1 dose of an investigational varicella vaccine (VNS) of low potency, 1 dose of a measles, mumps, and rubella (MMR) vaccine, 1 dose of a hepatitis A vaccine (Havrix) and 1 dose of a13 valent pneumococcal conjugate vaccine (Prevnar 13) on Day 1.
VNS_Low Group	Hepatitis A vaccine	Participants received 1 dose of an investigational varicella vaccine (VNS) of low potency, 1 dose of a measles, mumps, and rubella (MMR) vaccine, 1 dose of a hepatitis A vaccine (Havrix) and 1 dose of a13 valent pneumococcal conjugate vaccine (Prevnar 13) on Day 1.
VNS_Med Group	Investigational varicella vaccine medium potency	Participants received 1 dose of VNS vaccine of medium potency, 1 dose of MMR vaccine, 1 dose of Havrix vaccine, and 1 dose of Prevnar 13 vaccine on Day 1.
VNS_Med Group	Measles, mumps, and rubella vaccine	Participants received 1 dose of VNS vaccine of medium potency, 1 dose of MMR vaccine, 1 dose of Havrix vaccine, and 1 dose of Prevnar 13 vaccine on Day 1.
VNS_Med Group	Hepatitis A vaccine	Participants received 1 dose of VNS vaccine of medium potency, 1 dose of MMR vaccine, 1 dose of Havrix vaccine, and 1 dose of Prevnar 13 vaccine on Day 1.
VNS_High Group	Investigational varicella vaccine high potency	Participants received 1 dose of VNS vaccine of high potency, 1 dose of MMR vaccine, 1 dose of Havrix vaccine, and 1 dose of Prevnar 13 vaccine on Day 1.
VNS_High Group	Measles, mumps, and rubella vaccine	Participants received 1 dose of VNS vaccine of high potency, 1 dose of MMR vaccine, 1 dose of Havrix vaccine, and 1 dose of Prevnar 13 vaccine on Day 1.
VNS_High Group	Hepatitis A vaccine	Participants received 1 dose of VNS vaccine of high potency, 1 dose of MMR vaccine, 1 dose of Havrix vaccine, and 1 dose of Prevnar 13 vaccine on Day 1.
VV_Lot1 and Lot2 Pooled Group	Licensed varicella vaccine Lot 1	Participants received 1 dose of a licensed varicella vaccine (VV) of Lot 1 or 1 dose of a licensed vaccine (VV) of Lot 2, 1 dose of MMR vaccine, 1 dose of Havrix vaccine, and 1 dose of Prevnar 13 vaccine on Day 1.
VV_Lot1 and Lot2 Pooled Group	Licensed varicella vaccine Lot 2	Participants received 1 dose of a licensed varicella vaccine (VV) of Lot 1 or 1 dose of a licensed vaccine (VV) of Lot 2, 1 dose of MMR vaccine, 1 dose of Havrix vaccine, and 1 dose of Prevnar 13 vaccine on Day 1.
VV_Lot1 and Lot2 Pooled Group	Measles, mumps, and rubella vaccine	Participants received 1 dose of a licensed varicella vaccine (VV) of Lot 1 or 1 dose of a licensed vaccine (VV) of Lot 2, 1 dose of MMR vaccine, 1 dose of Havrix vaccine, and 1 dose of Prevnar 13 vaccine on Day 1.
VV_Lot1 and Lot2 Pooled Group	Hepatitis A vaccine	Participants received 1 dose of a licensed varicella vaccine (VV) of Lot 1 or 1 dose of a licensed vaccine (VV) of Lot 2, 1 dose of MMR vaccine, 1 dose of Havrix vaccine, and 1 dose of Prevnar 13 vaccine on Day 1.
VNS_Low Group	13-valent pneumococcal conjugate vaccine	Participants received 1 dose of an investigational varicella vaccine (VNS) of low potency, 1 dose of a measles, mumps, and rubella (MMR) vaccine, 1 dose of a hepatitis A vaccine (Havrix) and 1 dose of a13 valent pneumococcal conjugate vaccine (Prevnar 13) on Day 1.
VNS_Med Group	13-valent pneumococcal conjugate vaccine	Participants received 1 dose of VNS vaccine of medium potency, 1 dose of MMR vaccine, 1 dose of Havrix vaccine, and 1 dose of Prevnar 13 vaccine on Day 1.
VNS_High Group	13-valent pneumococcal conjugate vaccine	Participants received 1 dose of VNS vaccine of high potency, 1 dose of MMR vaccine, 1 dose of Havrix vaccine, and 1 dose of Prevnar 13 vaccine on Day 1.
VV_Lot1 and Lot2 Pooled Group	13-valent pneumococcal conjugate vaccine	Participants received 1 dose of a licensed varicella vaccine (VV) of Lot 1 or 1 dose of a licensed vaccine (VV) of Lot 2, 1 dose of MMR vaccine, 1 dose of Havrix vaccine, and 1 dose of Prevnar 13 vaccine on Day 1.
VNS_High Group	Investigational varicella vaccine high potency	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.
VV_Lot1 and Lot2 Pooled Group	Marketed varicella vaccine Lot 1	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.
VV_Lot1 and Lot2 Pooled Group	Measles, mumps, and rubella vaccine	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.
VNS_High Group	Measles, mumps, and rubella vaccine	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.
VNS_High Group	13-valent pneumococcal conjugate vaccine	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.
VNS_Low Group	Investigational varicella vaccine low potency	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.
VNS_Med Group	Hepatitis A vaccine	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.
VNS_Med Group	13-valent pneumococcal conjugate vaccine	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.
VNS_High Group	Hepatitis A vaccine	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.
VV_Lot1 and Lot2 Pooled Group	Marketed varicella vaccine Lot 2	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.
VNS_Low Group	Measles, mumps, and rubella vaccine	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.
VNS_Low Group	13-valent pneumococcal conjugate vaccine	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.
VNS_Med Group	Investigational varicella vaccine medium potency	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.
VNS_Med Group	Measles, mumps, and rubella vaccine	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.
VV_Lot1 and Lot2 Pooled Group	Hepatitis A vaccine	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.
VNS_Low Group	Hepatitis A vaccine	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.
VV_Lot1 and Lot2 Pooled Group	13-valent pneumococcal conjugate vaccine	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.

Primary Outcome Measures

Name	Time	Method
Concentrations of Anti-varicella Zoster Virus (VZV) Glycoprotein E (gE) Antibodies	At Day 43	Concentrations of anti-VZV gE antibodies were presented as Geometric Mean Concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL) for each group.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Seroresponse to VZV gE	At Day 43	Seroresponse was defined as the percentage of participants for whom the post-dose of anti VZV gE antibody concentration was greater than or equal to (\>=) 300 mIU/mL for each group.
Number of Participants Reporting Each Solicited Administration Site Events	Day 1 (post dose) to Day 4	Assessed solicited administration site events included injection site redness, pain and swelling.
Number of Participants Reporting Unsolicited Adverse Events	Day 1 (post dose) to Day 43	Unsolicited adverse events (AEs) included 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; these were assessed for each group after the administration of all vaccines. Unsolicited AEs included both serious and non-serious AEs.
Number of Participants Reporting Each Solicited Systemic Events	Day 1 (post dose) to Day 15	Solicited systemic events included drowsiness, loss of appetite, and irritability after the administration of all vaccines for each group.
Number of Participants Reporting Serious Adverse Events (SAEs)	From Day 1 to Day 181 (Study end)	A SAE was defined as an AE which was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, or other situations that were considered serious per medical or scientific judgment.