Measles, Mumps, Rubella, Varicella
Conditions
Keywords
second year of life, one-dose schedule, varicella, rubella, measles, mumps
Brief summary
This Phase 3b study is being conducted for the purpose of registration of the GSK208136 vaccine in Korea.
Interventions
BIOLOGICALPriorixTM
Subcutaneous administration in left upper arm
BIOLOGICALVarilrixTM
Subcutaneous administration in right upper arm
BIOLOGICALPriorix-Tetra®
Subcutaneous injection in left upper arm
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
11 Months to 24 Months
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study. * A male or female between, and including 11 and 24 months of age, at the time of the vaccination. * Written informed consent obtained from the parent or guardian of the subject. * Healthy subjects as established by medical history and clinical examination before entering into the study.
Exclusion criteria
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the dose of study vaccine, or planned use during the study period. * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose. * Administration of immunoglobulins and/or any blood products during the six months before entering the study or planned administration during the study period. * Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days prior to until 42 days after the study vaccine dose with the exception of inactivated vaccines such as pneumococcal, Haemophilus influenzae type b conjugate vaccines, inactivated influenza, hepatitis A or B vaccine or diphtheria/tetanus-containing vaccines which can be administered up to eight days before the study vaccine dose. * Previous vaccination against measles, mumps, rubella and/or varicella. * History of measles, mumps, rubella and/or varicella/zoster diseases. * Known exposure to measles, mumps, rubella and/or varicella within 30 days prior to study start. * Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection. * A family history of congenital or hereditary immunodeficiency. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s), including systemic hypersensitivity to neomycin. * Major congenital defects or serious chronic illness. * Acute disease at the time of enrolment. * Rectal temperature ≥ 38°C or axillary temperature ≥ 37.5°C at the time of vaccination. * Residence in the same household as a high risk person e.g.: * New-born infants (0-4 weeks of age) * Pregnant women who have a negative history of chickenpox * Persons with known immunodeficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Seroconverted for Measles, Mumps, Rubella and Varicella Zoster Virus (VZV) Antibodies Above the Cut-off Values | At 42 days post-vaccination | Seroconversion was defined as the appearance of antibodies \[i.e. titer greater than or equal to (≥) the cut-off value\] in the sera of subjects seronegative \[i.e. titer below (\<) cut-off value\] before vaccination. Cut-off values were the following: Anti-measles concentration ≥ 150 milli-international units per milliliter (mIU/mL); Anti-mumps concentration ≥ 231 units per milliliter (U/mL); Anti-rubella concentration ≥ 4 international units per milliliter (IU/mL); Anti-VZV titer ≥ 1:4 dilution. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antibody Concentrations Against Mumps | At 42-days post-vaccination | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in units per milliliter (U/mL). |
| Antibody Concentrations Against Rubella | At 42-days post-vaccination | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL). |
| Antibody Titers Against Varicela Viruses | At 42-days post-vaccination | Antibody titers were presented as geometric mean titers (GMTs). |
| Antibody Concentrations Against Measles | At 42-days post-vaccination | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL). |
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | During the 43-day (Days 0-42) post-vaccination period | Solicited general symptoms assessed were fever \[defined as rectal temperature ≥38.0 degrees Celsius (°C)\], rash, meningism and parotid gland swelling. Any= incidence of the specified symptoms regardless of intensity grade or relationship to study vaccine. Grade 3 fever= rectal temperature above (\>) 39.5°C. Grade 3 rash= more than 150 lesions. Grade 3 meningism and parotid gland swelling= meningism/parotid gland swelling symptom which prevented normal everyday activities. Related = general symptom assessed by the investigator as causally related to the vaccination. |
| Number of Subjects With Any Unsolicited Adverse Events (AEs) | Within the 43-day (Days 0-42) post-vaccination period | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any was defined as an adverse event (AE) reported in addition to those solicited during the clinical study. Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. |
| Number of Subjects With Serious Adverse Events (SAEs) | During the entire study period (from Day 0 up to Day 43 or Day 57) | Serious adverse events (SAEs) assessed include medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. |
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | During the 4-day (Days 0-3) post-vaccination period | Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cry when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site. |
Countries
South Korea
Participant flow
Recruitment details
Out of 475 subjects enrolled in the study, one did not receive any vaccination.
Pre-assignment details
During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.
Participants by arm
| Arm | Count |
|---|---|
| Priorix-Tetra Group Healthy male and female subjects between, and including 11 and 24 months of age, who received one dose of Priorix-Tetra® vaccine at Day 0, administered subcutaneously in the deltoid region of the left upper arm. | 313 |
| Priorix + Varilrix Group Healthy male and female subjects between, and including 11 and 24 months of age, who received one dose of Priorix™ vaccine together with one dose of Varilrix™ vaccine at Day 0, administered subcutaneously in the deltoid regions of the left or right upper arm, respectively. | 161 |
| Total | 474 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Migration from study area | 1 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | Priorix + Varilrix Group | Total | Priorix-Tetra Group |
|---|---|---|---|
| Age, Continuous | 12.5 Months STANDARD_DEVIATION 1.65 | 12.43 Months STANDARD_DEVIATION 1.49 | 12.4 Months STANDARD_DEVIATION 1.4 |
| Race/Ethnicity, Customized Asian-East Asian Heritage | 159 Participants | 472 Participants | 313 Participants |
| Race/Ethnicity, Customized Asian-South East Asian Heritage | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Female | 76 Participants | 204 Participants | 128 Participants |
| Sex: Female, Male Male | 85 Participants | 270 Participants | 185 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 313 | 0 / 161 |
| other Total, other adverse events | 243 / 313 | 113 / 161 |
| serious Total, serious adverse events | 25 / 313 | 12 / 161 |
Outcome results
Primary
Number of Subjects Seroconverted for Measles, Mumps, Rubella and Varicella Zoster Virus (VZV) Antibodies Above the Cut-off Values
Seroconversion was defined as the appearance of antibodies \[i.e. titer greater than or equal to (≥) the cut-off value\] in the sera of subjects seronegative \[i.e. titer below (\<) cut-off value\] before vaccination. Cut-off values were the following: Anti-measles concentration ≥ 150 milli-international units per milliliter (mIU/mL); Anti-mumps concentration ≥ 231 units per milliliter (U/mL); Anti-rubella concentration ≥ 4 international units per milliliter (IU/mL); Anti-VZV titer ≥ 1:4 dilution.
Time frame: At 42 days post-vaccination
Population: The analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity,which included all evaluable subjects who were seronegative for at least one vaccine antigen at baseline and for whom pre-vaccination and post-vaccination serology results were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Priorix-Tetra Group | Number of Subjects Seroconverted for Measles, Mumps, Rubella and Varicella Zoster Virus (VZV) Antibodies Above the Cut-off Values | Anti-Measles | 294 Participants |
| Priorix-Tetra Group | Number of Subjects Seroconverted for Measles, Mumps, Rubella and Varicella Zoster Virus (VZV) Antibodies Above the Cut-off Values | Anti-Mumps | 262 Participants |
| Priorix-Tetra Group | Number of Subjects Seroconverted for Measles, Mumps, Rubella and Varicella Zoster Virus (VZV) Antibodies Above the Cut-off Values | Anti-Rubella | 297 Participants |
| Priorix-Tetra Group | Number of Subjects Seroconverted for Measles, Mumps, Rubella and Varicella Zoster Virus (VZV) Antibodies Above the Cut-off Values | Anti-VZV | 280 Participants |
| Priorix + Varilrix Group | Number of Subjects Seroconverted for Measles, Mumps, Rubella and Varicella Zoster Virus (VZV) Antibodies Above the Cut-off Values | Anti-VZV | 151 Participants |
| Priorix + Varilrix Group | Number of Subjects Seroconverted for Measles, Mumps, Rubella and Varicella Zoster Virus (VZV) Antibodies Above the Cut-off Values | Anti-Measles | 155 Participants |
| Priorix + Varilrix Group | Number of Subjects Seroconverted for Measles, Mumps, Rubella and Varicella Zoster Virus (VZV) Antibodies Above the Cut-off Values | Anti-Rubella | 157 Participants |
| Priorix + Varilrix Group | Number of Subjects Seroconverted for Measles, Mumps, Rubella and Varicella Zoster Virus (VZV) Antibodies Above the Cut-off Values | Anti-Mumps | 145 Participants |
Comparison: Non-inferiority of Priorix-Tetra® vaccine vs Priorix™ and Varilrix™ administered as concomitant vaccine 42-56 days after vaccination at Day 0 in terms of anti-measles seroconversion rates.p-value: <0.0595% CI: [-3.77, 1.66]Fisher Exact
Comparison: Non-inferiority of Priorix-Tetra® vaccine vs Priorix™ and Varilrix™ administered as concomitant vaccine 42-56 days after vaccination at Day 0 in terms of anti-mumps seroconversion rates.p-value: <0.0595% CI: [-10.4, 0.38]Fisher Exact
Comparison: Non-inferiority of Priorix-Tetra® vaccine vs Priorix™ and Varilrix™ administered as concomitant vaccine 42-56 days after vaccination at Day 0 in terms of anti-rubella seroconversion rates.p-value: <0.0595% CI: [-1.88, 2.06]Fisher Exact
Comparison: Non-inferiority of Priorix-Tetra® vaccine vs Priorix™ and Varilrix™ administered as concomitant vaccine 42-56 days after vaccination at Day 0 in terms of anti-varicella zoster virus (anti-VZV) seroconversion rates.p-value: <0.0595% CI: [-3.07, 1.44]Fisher Exact
Secondary
Antibody Concentrations Against Measles
Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL).
Time frame: At 42-days post-vaccination
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects who were seronegative for at least one vaccine antigen at baseline and for whom pre-vaccination and post-vaccination serology results were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Priorix-Tetra Group | Antibody Concentrations Against Measles | 4978.6 mIU/mL |
| Priorix + Varilrix Group | Antibody Concentrations Against Measles | 3433.6 mIU/mL |
Secondary
Antibody Concentrations Against Mumps
Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in units per milliliter (U/mL).
Time frame: At 42-days post-vaccination
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects who were seronegative for at least one vaccine antigen at baseline and for whom pre-vaccination and post-vaccination serology results were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Priorix-Tetra Group | Antibody Concentrations Against Mumps | 1012.3 U/mL |
| Priorix + Varilrix Group | Antibody Concentrations Against Mumps | 934.3 U/mL |
Secondary
Antibody Concentrations Against Rubella
Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL).
Time frame: At 42-days post-vaccination
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects who were seronegative for at least one vaccine antigen at baseline and for whom pre-vaccination and post-vaccination serology results were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Priorix-Tetra Group | Antibody Concentrations Against Rubella | 63.4 IU/mL |
| Priorix + Varilrix Group | Antibody Concentrations Against Rubella | 75.7 IU/mL |
Secondary
Antibody Titers Against Varicela Viruses
Antibody titers were presented as geometric mean titers (GMTs).
Time frame: At 42-days post-vaccination
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects who were seronegative for at least one vaccine antigen at baseline and for whom pre-vaccination and post-vaccination serology results were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Priorix-Tetra Group | Antibody Titers Against Varicela Viruses | 134.1 Titers |
| Priorix + Varilrix Group | Antibody Titers Against Varicela Viruses | 129.2 Titers |
Secondary
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cry when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Time frame: During the 4-day (Days 0-3) post-vaccination period
Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects who had their symptoms sheet filled in.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Priorix-Tetra Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain | 15 Participants |
| Priorix-Tetra Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain | 0 Participants |
| Priorix-Tetra Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness | 26 Participants |
| Priorix-Tetra Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness | 0 Participants |
| Priorix-Tetra Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling | 5 Participants |
| Priorix-Tetra Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling | 0 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling | 5 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain | 10 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness | 1 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain | 0 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling | 0 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness | 21 Participants |
Secondary
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Solicited general symptoms assessed were fever \[defined as rectal temperature ≥38.0 degrees Celsius (°C)\], rash, meningism and parotid gland swelling. Any= incidence of the specified symptoms regardless of intensity grade or relationship to study vaccine. Grade 3 fever= rectal temperature above (\>) 39.5°C. Grade 3 rash= more than 150 lesions. Grade 3 meningism and parotid gland swelling= meningism/parotid gland swelling symptom which prevented normal everyday activities. Related = general symptom assessed by the investigator as causally related to the vaccination.
Time frame: During the 43-day (Days 0-42) post-vaccination period
Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects who had the symptoms sheet filled in.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Priorix-Tetra Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Temperature | 31 Participants |
| Priorix-Tetra Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Temperature | 202 Participants |
| Priorix-Tetra Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Temperature | 53 Participants |
| Priorix-Tetra Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Rash | 33 Participants |
| Priorix-Tetra Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Rash | 0 Participants |
| Priorix-Tetra Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Rash | 3 Participants |
| Priorix-Tetra Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Meningism | 2 Participants |
| Priorix-Tetra Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Meningism | 0 Participants |
| Priorix-Tetra Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Meningism | 0 Participants |
| Priorix-Tetra Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Parotid gland swelling | 0 Participants |
| Priorix-Tetra Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Parotid gland swelling | 0 Participants |
| Priorix-Tetra Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Parotid gland swelling | 0 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Rash | 1 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Parotid gland swelling | 0 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Meningism | 0 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Temperature | 82 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Meningism | 0 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Temperature | 19 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Temperature | 12 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Parotid gland swelling | 0 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Rash | 16 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Meningism | 0 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Rash | 0 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Parotid gland swelling | 0 Participants |
Secondary
Number of Subjects With Any Unsolicited Adverse Events (AEs)
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any was defined as an adverse event (AE) reported in addition to those solicited during the clinical study. Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.
Time frame: Within the 43-day (Days 0-42) post-vaccination period
Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Priorix-Tetra Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 194 Participants |
| Priorix + Varilrix Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 88 Participants |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: During the entire study period (from Day 0 up to Day 43 or Day 57)
Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Priorix-Tetra Group | Number of Subjects With Serious Adverse Events (SAEs) | 25 Participants |
| Priorix + Varilrix Group | Number of Subjects With Serious Adverse Events (SAEs) | 12 Participants |