Chickenpox
Conditions
Keywords
Varicella, Chickenpox
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.
Interventions
BIOLOGICALInvestigational varicella vaccine low potency
1 dose of a low-potency investigational varicella vaccine administered subcutaneously.
BIOLOGICALInvestigational varicella vaccine medium potency
1 dose of a medium-potency investigational varicella vaccine administered subcutaneously.
BIOLOGICALInvestigational varicella vaccine high potency
1 dose of a high-potency investigational varicella vaccine administered subcutaneously.
BIOLOGICALLicensed varicella vaccine Lot 1
1 dose of a licensed varicella vaccine of Lot 1 administered subcutaneously.
BIOLOGICALLicensed varicella vaccine Lot 2
1 dose of a licensed varicella vaccine of Lot 2 administered subcutaneously.
BIOLOGICALMeasles, mumps, and rubella vaccine
1 dose of a measles, mumps, and rubella vaccine administered subcutaneously.
BIOLOGICALHepatitis A vaccine
1 dose of a hepatitis A vaccine administered intramuscularly.
BIOLOGICAL13-valent pneumococcal conjugate vaccine
1 dose of a 13-valent pneumococcal conjugate vaccine administered intramuscularly.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Observer-blind study. Recipients and study evaluators will be unaware of vaccine administered.
Eligibility
Sex/Gender
ALL
Age
12 Months to 15 Months
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 Each Solicited Systemic Events | Day 1 (post dose) to Day 43 | Solicited systemic events included fever, varicella like rash (including injection site varicella-like rash), and general rash (not varicella-like) after the administration of all vaccines for each group. Fever was defined as temperature \>= 38.0 °C (100.4°F) by any route (the preferred location for measuring temperature is the axilla). A typical varicella-like rash manifests as a rash/lesion that may appear within several weeks after the varicella vaccination. Lesions may contain spots, bumps, blisters, or crusts. Includes injection site varicella-like rash. |
| 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 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. |
Countries
Estonia, Poland, Puerto Rico, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Out of 800 participants enrolled, 9 participants discontinued before receiving the vaccination and therefore only 791 participants were included in the Exposed Set and started the study.
Pre-assignment details
* The Prevnar 13 vaccine was administered only to participants enrolled in the US and in countries where pneumococcal conjugate vaccine is recommended at 12- 15 months as per national immunization schedule. * As described in the protocol and analysis plan, participants in the varicella vaccine (VV) group are randomized into two lots (VV\_Lot1 and VV\_Lot2) and analyzed as pooled throughout the study.
Participants by arm
| Arm | Count |
|---|---|
| VNS_Low Group 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\. | 203 |
| VNS_Med Group 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. | 195 |
| VNS_High Group 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. | 203 |
| VV_Lot1 and Lot2 Pooled Group 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. | 190 |
| Total | 791 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 6 | 3 | 7 | 3 |
| Overall Study | Other | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 3 | 1 |
Baseline characteristics
| Characteristic | VNS_Low Group | VNS_Med Group | VNS_High Group | VV_Lot1 and Lot2 Pooled Group | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 203 Participants | 195 Participants | 203 Participants | 190 Participants | 791 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 75 Participants | 71 Participants | 74 Participants | 73 Participants | 293 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic nor Latino | 128 Participants | 124 Participants | 128 Participants | 117 Participants | 497 Participants |
| Sex: Female, Male Female | 114 Participants | 102 Participants | 101 Participants | 107 Participants | 424 Participants |
| Sex: Female, Male Male | 89 Participants | 93 Participants | 102 Participants | 83 Participants | 367 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 203 | 0 / 195 | 0 / 203 | 0 / 190 |
| other Total, other adverse events | 173 / 203 | 165 / 195 | 178 / 203 | 158 / 190 |
| serious Total, serious adverse events | 2 / 203 | 4 / 195 | 4 / 203 | 6 / 190 |
Outcome results
Primary
Concentrations of Anti-varicella Zoster Virus (VZV) Glycoprotein E (gE) Antibodies
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.
Time frame: At Day 43
Population: The analysis was performed on the Per Protocol Set (PPS), which included participants who received all study interventions as per protocol, were not unblinded, had immunogenicity results post-dose, complied with blood draw intervals, without intercurrent medical conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| VNS_Low Group | Concentrations of Anti-varicella Zoster Virus (VZV) Glycoprotein E (gE) Antibodies | 960 mlU/ml |
| VNS_Med Group | Concentrations of Anti-varicella Zoster Virus (VZV) Glycoprotein E (gE) Antibodies | 1071 mlU/ml |
| VNS_High Group | Concentrations of Anti-varicella Zoster Virus (VZV) Glycoprotein E (gE) Antibodies | 1555 mlU/ml |
| VV_Lot1 and Lot2 Pooled Group | Concentrations of Anti-varicella Zoster Virus (VZV) Glycoprotein E (gE) Antibodies | 1284 mlU/ml |
Secondary
Number of Participants Reporting Each Solicited Administration Site Events
Assessed solicited administration site events included injection site redness, pain and swelling.
Time frame: Day 1 (post dose) to Day 4
Population: The analysis was performed on the Exposed set (ES), which included all participants who received a study intervention. Analysis per group was based on the varicella intervention administered.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VNS_Low Group | Number of Participants Reporting Each Solicited Administration Site Events | Swelling at injection site | 14 Participants |
| VNS_Low Group | Number of Participants Reporting Each Solicited Administration Site Events | Injection site pain | 76 Participants |
| VNS_Low Group | Number of Participants Reporting Each Solicited Administration Site Events | Redness at injection site | 24 Participants |
| VNS_Med Group | Number of Participants Reporting Each Solicited Administration Site Events | Redness at injection site | 23 Participants |
| VNS_Med Group | Number of Participants Reporting Each Solicited Administration Site Events | Injection site pain | 64 Participants |
| VNS_Med Group | Number of Participants Reporting Each Solicited Administration Site Events | Swelling at injection site | 11 Participants |
| VNS_High Group | Number of Participants Reporting Each Solicited Administration Site Events | Redness at injection site | 35 Participants |
| VNS_High Group | Number of Participants Reporting Each Solicited Administration Site Events | Injection site pain | 70 Participants |
| VNS_High Group | Number of Participants Reporting Each Solicited Administration Site Events | Swelling at injection site | 15 Participants |
| VV_Lot1 and Lot2 Pooled Group | Number of Participants Reporting Each Solicited Administration Site Events | Injection site pain | 57 Participants |
| VV_Lot1 and Lot2 Pooled Group | Number of Participants Reporting Each Solicited Administration Site Events | Swelling at injection site | 12 Participants |
| VV_Lot1 and Lot2 Pooled Group | Number of Participants Reporting Each Solicited Administration Site Events | Redness at injection site | 23 Participants |
Secondary
Number of Participants Reporting Each Solicited Systemic Events
Solicited systemic events included fever, varicella like rash (including injection site varicella-like rash), and general rash (not varicella-like) after the administration of all vaccines for each group. Fever was defined as temperature \>= 38.0 °C (100.4°F) by any route (the preferred location for measuring temperature is the axilla). A typical varicella-like rash manifests as a rash/lesion that may appear within several weeks after the varicella vaccination. Lesions may contain spots, bumps, blisters, or crusts. Includes injection site varicella-like rash.
Time frame: Day 1 (post dose) to Day 43
Population: The analysis was performed on the ES, which included all participants who received a study intervention. Analysis per group was based on the varicella intervention administered.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VNS_Low Group | Number of Participants Reporting Each Solicited Systemic Events | Fever | 49 Participants |
| VNS_Low Group | Number of Participants Reporting Each Solicited Systemic Events | Any general rash | 66 Participants |
| VNS_Low Group | Number of Participants Reporting Each Solicited Systemic Events | Any varicella-like rash | 33 Participants |
| VNS_Med Group | Number of Participants Reporting Each Solicited Systemic Events | Fever | 48 Participants |
| VNS_Med Group | Number of Participants Reporting Each Solicited Systemic Events | Any general rash | 51 Participants |
| VNS_Med Group | Number of Participants Reporting Each Solicited Systemic Events | Any varicella-like rash | 31 Participants |
| VNS_High Group | Number of Participants Reporting Each Solicited Systemic Events | Any varicella-like rash | 35 Participants |
| VNS_High Group | Number of Participants Reporting Each Solicited Systemic Events | Fever | 59 Participants |
| VNS_High Group | Number of Participants Reporting Each Solicited Systemic Events | Any general rash | 68 Participants |
| VV_Lot1 and Lot2 Pooled Group | Number of Participants Reporting Each Solicited Systemic Events | Fever | 44 Participants |
| VV_Lot1 and Lot2 Pooled Group | Number of Participants Reporting Each Solicited Systemic Events | Any general rash | 59 Participants |
| VV_Lot1 and Lot2 Pooled Group | Number of Participants Reporting Each Solicited Systemic Events | Any varicella-like rash | 29 Participants |
Secondary
Number of Participants Reporting Each Solicited Systemic Events
Solicited systemic events included drowsiness, loss of appetite, and irritability after the administration of all vaccines for each group.
Time frame: Day 1 (post dose) to Day 15
Population: The analysis was performed on the ES, which included all participants who received a study intervention. Analysis per group was based on the varicella intervention administered.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VNS_Low Group | Number of Participants Reporting Each Solicited Systemic Events | Any drowsiness | 86 Participants |
| VNS_Low Group | Number of Participants Reporting Each Solicited Systemic Events | Any irritability | 112 Participants |
| VNS_Low Group | Number of Participants Reporting Each Solicited Systemic Events | Any loss of appetite | 69 Participants |
| VNS_Med Group | Number of Participants Reporting Each Solicited Systemic Events | Any drowsiness | 68 Participants |
| VNS_Med Group | Number of Participants Reporting Each Solicited Systemic Events | Any irritability | 94 Participants |
| VNS_Med Group | Number of Participants Reporting Each Solicited Systemic Events | Any loss of appetite | 57 Participants |
| VNS_High Group | Number of Participants Reporting Each Solicited Systemic Events | Any loss of appetite | 71 Participants |
| VNS_High Group | Number of Participants Reporting Each Solicited Systemic Events | Any drowsiness | 93 Participants |
| VNS_High Group | Number of Participants Reporting Each Solicited Systemic Events | Any irritability | 112 Participants |
| VV_Lot1 and Lot2 Pooled Group | Number of Participants Reporting Each Solicited Systemic Events | Any drowsiness | 80 Participants |
| VV_Lot1 and Lot2 Pooled Group | Number of Participants Reporting Each Solicited Systemic Events | Any irritability | 109 Participants |
| VV_Lot1 and Lot2 Pooled Group | Number of Participants Reporting Each Solicited Systemic Events | Any loss of appetite | 60 Participants |
Secondary
Number of Participants Reporting Serious Adverse Events (SAEs)
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.
Time frame: From Day 1 to Day 181 (Study end)
Population: The analysis was performed on the ES, which included all participants who received a study intervention. Analysis per group was based on the varicella intervention administered.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VNS_Low Group | Number of Participants Reporting Serious Adverse Events (SAEs) | 2 Participants |
| VNS_Med Group | Number of Participants Reporting Serious Adverse Events (SAEs) | 4 Participants |
| VNS_High Group | Number of Participants Reporting Serious Adverse Events (SAEs) | 4 Participants |
| VV_Lot1 and Lot2 Pooled Group | Number of Participants Reporting Serious Adverse Events (SAEs) | 6 Participants |
Secondary
Number of Participants Reporting Unsolicited Adverse Events
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.
Time frame: Day 1 (post dose) to Day 43
Population: The analysis was performed on the ES, which included all participants who received a study intervention. Analysis per group was based on the varicella intervention administered.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VNS_Low Group | Number of Participants Reporting Unsolicited Adverse Events | 67 Participants |
| VNS_Med Group | Number of Participants Reporting Unsolicited Adverse Events | 53 Participants |
| VNS_High Group | Number of Participants Reporting Unsolicited Adverse Events | 64 Participants |
| VV_Lot1 and Lot2 Pooled Group | Number of Participants Reporting Unsolicited Adverse Events | 61 Participants |
Secondary
Percentage of Participants With Seroresponse to VZV gE
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.
Time frame: At Day 43
Population: The analysis was performed on the PPS, which included participants who received all study interventions as per protocol, were not unblinded, had immunogenicity results post-dose, complied with blood draw intervals, without intercurrent medical conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VNS_Low Group | Percentage of Participants With Seroresponse to VZV gE | 93.6 Percentage of participants |
| VNS_Med Group | Percentage of Participants With Seroresponse to VZV gE | 96.2 Percentage of participants |
| VNS_High Group | Percentage of Participants With Seroresponse to VZV gE | 98.7 Percentage of participants |
| VV_Lot1 and Lot2 Pooled Group | Percentage of Participants With Seroresponse to VZV gE | 98.1 Percentage of participants |