Acellular Pertussis, Diphtheria, Tetanus
Conditions
Keywords
Co-administration, Immunization, Preschool, Booster
Brief summary
The purpose of the study is to evaluate the immunogenicity and safety of Kinrix when co-administered with varicella (Varivax® \[varicella virus vaccine live\], Merck and Company) and (measles mumps rubella) MMR vaccines, compared to Kinrix co-administered with MMR vaccine alone. Both Kinrix and the second dose of Varivax are indicated in children 4-6 years of age, and there is great potential for the vaccines to be given concurrently. The aim of this trial is to demonstrate that co-administered Varivax does not negatively affect the immunogenicity or reactogenicity of Kinrix.
Detailed description
Subjects 4-6 years of age will be randomized into two groups to receive either Kinrix, Varivax and M-M-RII on day 0 (Group 1) or Kinrix and M-M-RII on day 0 and Varivax at month 1(Group 2). All subjects in both groups to provide blood samples prior to vaccination on day 0 and at month 1 (for Group 2, blood sampling is prior to vaccination with Varivax). Duration of the study will be approximately 6 months for each subject with a safety telephone contact 6 months after vaccinations.
Interventions
BIOLOGICALGSK Biologicals'Kinrix®
One dose as intramuscular injection at visit 1
BIOLOGICALMerck and Company's MMRII
One dose as subcutaneous injection at visit 1
BIOLOGICALMerck and Company's Varivax
One dose as subcutaneous injection at visit 1 or at visit 2
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 6 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects for whom the investigator believes that their parents/ guardians can and will comply with the requirements of the protocol. * A male or female child between 4 and 6 years of age, inclusive. * 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. * Having received 4 doses of (Diphtheria, Tetanus Acellular Pertussis) DTaP vaccine using Pediarix and/or Infanrix, and 3 doses of poliovirus vaccine using Pediarix and/or (inactivated poliovirus vaccine, Aventis Pasteur) IPOL in the first 2 years of life. * Previously received 1 dose of M-M-RII and Varivax (separate or combined) in the second year of life.
Exclusion criteria
* Use of any investigational or non-registered drug or vaccine other than the study vaccines within 30 days preceding the administration of study vaccines, or planned use during the study period. * Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or non-investigational product or device. * History of previous or intercurrent diphtheria, tetanus, pertussis, polio, measles, mumps, rubella or varicella disease, or of vaccination against these diseases given after the second year of life. * Known exposure to diphtheria, tetanus, pertussis, or polio, prior to vaccination. * Poliovirus vaccination with one or more doses of (oral polio virus) OPV vaccine. * Administration or planned administration of a vaccine not foreseen by the study protocol within 30 days of study vaccination and ending at Day 30. * Chronic administration or planned administration of immunosuppressants or other immune modifying drugs within six months prior to study vaccination or planned administration during the study period ending at Day 30. * Administration of immunoglobulins and/or any blood products at any time prior to study vaccination or planned administration during the study period ending at Day 30. * Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection. * History of seizures or progressive neurological disorder, including infantile spasms, uncontrolled epilepsy or progressive encephalopathy. * Major congenital defects or serious chronic illness. * Acute disease at the time of enrolment. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s). * History of anaphylactic reaction to egg proteins or previous doses of the vaccine(s). * Encephalopathy within 7 days of administration of previous dose of Infanrix or Pediarix. * Fever \>=40.5°C or 104.9°F (rectal temperature) (39.5°C or 103.1°F, oral/axillary) within 48 hours of previous dose of Infanrix or Pediarix not due to another identifiable cause. * Collapse or shock-like state within 48 hours of previous dose of DTaP or DTaP-containing vaccine. * Persistent, severe, inconsolable screaming or crying lasting ³3 hours occurring within 48 hours of administration of previous dose of DTaP or DTaP-containing vaccine. * Thrombocytopenia following a previous dose of M-M-RII or its component vaccines * Inability to contact a parent/guardian of the subject by telephone. * Blood dyscrasias, leukemia, lymphomas or other malignant neoplasms affecting the bone marrow or lymphatic systems. * Family history of congenital or hereditary immunodeficiency, unless the immune competence of the subject has been demonstrated. * Residence in the same household as the following persons: * New-born infants (0-4 weeks of age). * Pregnant mother/women without documented positive history of chickenpox disease or laboratory evidence of prior varicella vaccination. * Pregnant women at or beyond 28 weeks gestation regardless of varicella vaccination status or varicella disease history. * Persons with known immunodeficiency. * Active untreated tuberculosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Booster Responses to Diphteria and Tetanus | One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. | Anti-diphteria (anti-D) and anti-tetanus (anti-T) booster response was defined as: * initially seronegative subjects (sero-) (pre-booster antibody concentration below cut-off of \< 0.1 international units per milliliter (IU/mL)) with an increase of at least four times the cut-off one month after vaccination (post-booster antibody concentration ≥0.4 IU/mL) * initially seropositive subjects (sero+) (pre-booster antibody concentration ≥0.1 IU/mL) with an increase of at least four times the pre-booster antibody concentration one month after vaccination |
| Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (Anti-PRN) Booster Responses, Measured in Enzyme-Linked Immunosorbent Assay Units Per Milliliter (EL.U/mL) | One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. | anti-PT, anti-FHA and anti-PRN booster response : * initially sero- (pre-booster antibody concentration below cut-off \< 5.0 EL.U/mL) with increase of at least four times cut-off one month after vaccination (concentration post-booster ≥20.0 EL.U/mL) * initially sero+ with pre-booster antibody concentration ≥5.0 EL.U/mL and \< 20.0 EL.U/mL with increase of at least four times pre-booster concentration one month post-booster * initially sero+ with pre-booster antibody concentration ≥20.0 EL.U/mL with an increase of at least two times the pre-booster antibody concentration one month post-booster |
| Geometric Mean Titers (GMTs) for Antibodies to Poliovirus Types 1, 2 and 3 | One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. | Titers are expressed as GMTs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With an Anti-polio 1, 2, 3 Booster Response | One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. | Anti-poliovirus 1, anti-poliovirus 2 and anti-poliovirus 3 booster response: * initially seronegative subjects (pre-booster antibody titer below cut-off of 8 ED50) with an antibody titer ≥ 32 ED50 one month after vaccination * initially seropositive subjects (pre-booster antibody titers ≥ 8 ED50) with an increase at least four times the pre-booster antibody titer one month after vaccination. ED50 is defined here as the reverse of the dilution resulting in 50% inhibition. The lowest dilution at which serum samples were tested is 1:8 from which a test was considered positive. |
| Number of Subjects Seroprotected Against Diphteria and Tetanus | One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. | Seroprotection status was defined as: * anti-D antibody concentration greater than or equal to 0.1 IU/mL * anti-T antibody concentration greater than or equal to 0.1 IU/mL |
| Number of Subjects Protected Against Poliovirus 1, 2 and 3 | One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. | Seroprotection was defined: \* anti-poliovirus type 1, 2 or 3 antibody titer greater than or equal to 8 ED50. ED50 is defined here as the reverse of the dilution resulting in 50% inhibition. |
| Number of Subjects Seropositive for Anti-PT, Anti-FHA and Anti-PRN Antibodies | One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. | Seropositivity was defined as a concentration greater than or equal to 5.0 EL.U/mL |
| Number of Subjects With Anti-D and Anti-T Antibody Concentrations Above Cut-off Value | One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. | Cut-off value was defined as greater than or equal to 1.0 international units per milliliter (IU/mL). |
| Number of Subjects With Any Solicited General Symptoms | Within 4 days (Day 0 to 3) after booster immunization * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax | Solicited general symptoms included fever \[temperature equal to or greater than 37.5 degrees Celsius (°C)\], drowsiness and loss of appetite. Any was defined as incidence of a particular symptom regardless of intensity grade. |
| Number of Subjects With Unsolicited Adverse Events | Up to 31 days (Day 0 through Day 30) after booster vaccination * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax | An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event. |
| Number of Subjects With Serious Adverse Events (SAEs) | During the entire study period (from Day 0 to 6 months post-vaccination) | Serious adverse events are medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. |
| Number of Subjects With Any Solicited Local Symptoms | Within 4 days (Day 0 to 3) after booster immunization * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax | Solicited local symptoms included pain, redness and swelling at the injection site. Any was defined as incidence of a particular symptom regardless of intensity grade. |
| Geometric Mean Concentrations (GMCs) for Anti-D and Anti-T Antibodies | One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. | Concentrations were expressed as GMCs in IU/mL. |
| GMCs for Anti-PT, Anti-FHA, Anti-PRN Antibodies | One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. | Concentrations are expressed as GMCs in Enzyme-Linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL). |
Countries
United States
Participant flow
Pre-assignment details
478 subjects were enrolled, but 2 subjects who received a subject number were not vaccinated. Therefore the total amount of subjects used for the analysis was 476.
Participants by arm
| Arm | Count |
|---|---|
| Kinrix + M-M-R II + Varivax Subjects received at Day 0 one dose of Kinrix, intramuscularly in the deltoid region of the left upper arm, co-administered with one dose of M-M-R II and Varivax each, subcutaneously in the deltoid of the right upper and lower arm, respectively. | 239 |
| Kinrix + M-M-R II -> Varivax Subjects received at Day 0 one dose of Kinrix, intramuscularly in the deltoid region of the left upper arm, co-administered with one dose of M-M-R II, subcutaneously in the deltoid of the right upper arm. At Day 30 they received one dose of Varivax subcutaneously in the deltoid region of the right upper arm. | 237 |
| Total | 476 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 6 |
| Overall Study | Other | 0 | 4 |
Baseline characteristics
| Characteristic | Kinrix + M-M-R II -> Varivax | Total | Kinrix + M-M-R II + Varivax |
|---|---|---|---|
| Age, Continuous | 4.2 Years STANDARD_DEVIATION 0.37 | 4.2 Years STANDARD_DEVIATION 0.39 | 4.2 Years STANDARD_DEVIATION 0.41 |
| Race/Ethnicity, Customized African Heritage / African American | 23 Participants | 50 Participants | 27 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 33 Participants | 68 Participants | 35 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 11 Participants | 18 Participants | 7 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 5 Participants | 8 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 17 Participants | 30 Participants | 13 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 3 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized Unspecified | 32 Participants | 74 Participants | 42 Participants |
| Race/Ethnicity, Customized White - Arabic / North African Heritage | 6 Participants | 7 Participants | 1 Participants |
| Race/Ethnicity, Customized White - Caucasian / European Heritage | 107 Participants | 216 Participants | 109 Participants |
| Sex: Female, Male Female | 123 Participants | 252 Participants | 129 Participants |
| Sex: Female, Male Male | 114 Participants | 224 Participants | 110 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 239 | 0 / 237 |
| other Total, other adverse events | 228 / 230 | 230 / 230 |
| serious Total, serious adverse events | 0 / 239 | 1 / 237 |
Outcome results
Primary
Geometric Mean Titers (GMTs) for Antibodies to Poliovirus Types 1, 2 and 3
Titers are expressed as GMTs.
Time frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Population: Analysis was performed on the according-to-protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Kinrix + M-M-R II + Varivax | Geometric Mean Titers (GMTs) for Antibodies to Poliovirus Types 1, 2 and 3 | Anti-Polio 1 | 1638.4 titer |
| Kinrix + M-M-R II + Varivax | Geometric Mean Titers (GMTs) for Antibodies to Poliovirus Types 1, 2 and 3 | Anti-Polio 2 | 1572.9 titer |
| Kinrix + M-M-R II + Varivax | Geometric Mean Titers (GMTs) for Antibodies to Poliovirus Types 1, 2 and 3 | Anti-Polio 3 | 2588.4 titer |
| Kinrix + M-M-R II -> Varivax | Geometric Mean Titers (GMTs) for Antibodies to Poliovirus Types 1, 2 and 3 | Anti-Polio 1 | 1789.9 titer |
| Kinrix + M-M-R II -> Varivax | Geometric Mean Titers (GMTs) for Antibodies to Poliovirus Types 1, 2 and 3 | Anti-Polio 2 | 1902.6 titer |
| Kinrix + M-M-R II -> Varivax | Geometric Mean Titers (GMTs) for Antibodies to Poliovirus Types 1, 2 and 3 | Anti-Polio 3 | 3189.6 titer |
Comparison: To demonstrate the non-inferiority of DTaP-IPV vaccine co-administered with Varicella and MMR vaccines compared to DTaP-IPV vaccine co-administered with MMR only in terms of poliovirus type 1 geometric mean titers (GMTs), one month after vaccination with DTaP-IPV vaccine.95% CI: [0.76, 1.1]
Comparison: To demonstrate the non-inferiority of DTaP-IPV vaccine co-administered with Varicella and MMR vaccines compared to DTaP-IPV vaccine co-administered with MMR only in terms of poliovirus type 2 geometric mean titers (GMTs), one month after vaccination with DTaP-IPV vaccine.95% CI: [0.7, 0.99]
Comparison: To demonstrate the non-inferiority of DTaP-IPV vaccine co-administered with Varicella and MMR vaccines compared to DTaP-IPV vaccine co-administered with MMR only in terms of poliovirus type 3 geometric mean titers (GMTs), one month after vaccination with DTaP-IPV vaccine.95% CI: [0.71, 1.01]
Primary
Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (Anti-PRN) Booster Responses, Measured in Enzyme-Linked Immunosorbent Assay Units Per Milliliter (EL.U/mL)
anti-PT, anti-FHA and anti-PRN booster response : * initially sero- (pre-booster antibody concentration below cut-off \< 5.0 EL.U/mL) with increase of at least four times cut-off one month after vaccination (concentration post-booster ≥20.0 EL.U/mL) * initially sero+ with pre-booster antibody concentration ≥5.0 EL.U/mL and \< 20.0 EL.U/mL with increase of at least four times pre-booster concentration one month post-booster * initially sero+ with pre-booster antibody concentration ≥20.0 EL.U/mL with an increase of at least two times the pre-booster antibody concentration one month post-booster
Time frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Population: Analysis was performed on the according-to-protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Kinrix + M-M-R II + Varivax | Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (Anti-PRN) Booster Responses, Measured in Enzyme-Linked Immunosorbent Assay Units Per Milliliter (EL.U/mL) | Anti-PT | 207 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (Anti-PRN) Booster Responses, Measured in Enzyme-Linked Immunosorbent Assay Units Per Milliliter (EL.U/mL) | Anti-FHA | 213 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (Anti-PRN) Booster Responses, Measured in Enzyme-Linked Immunosorbent Assay Units Per Milliliter (EL.U/mL) | Anti-PRN | 220 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (Anti-PRN) Booster Responses, Measured in Enzyme-Linked Immunosorbent Assay Units Per Milliliter (EL.U/mL) | Anti-PRN | 209 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (Anti-PRN) Booster Responses, Measured in Enzyme-Linked Immunosorbent Assay Units Per Milliliter (EL.U/mL) | Anti-PT | 201 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (Anti-PRN) Booster Responses, Measured in Enzyme-Linked Immunosorbent Assay Units Per Milliliter (EL.U/mL) | Anti-FHA | 209 Participants |
Comparison: To demonstrate the non-inferiority of DTaP-IPV vaccine co-administered with Varicella and MMR vaccines compared to DTaP-IPV vaccine co-administered with MMR only in terms of pertussis toxoid (PT) booster response one month after vaccination with DTaP-IPV vaccine.95% CI: [-5.07, 3.51]
Comparison: To demonstrate the non-inferiority of DTaP-IPV vaccine co-administered with Varicella and MMR vaccines compared to DTaP-IPV vaccine co-administered with MMR only in terms of filamentous hemagglutinin (FHA) booster response one month after vaccination with DTaP-IPV vaccine.95% CI: [-3.59, 1.39]
Comparison: To demonstrate the non-inferiority of DTaP-IPV vaccine co-administered with Varicella and MMR vaccines compared to DTaP-IPV vaccine co-administered with MMR only in terms of pertactin (PRN) booster response one month after vaccination with DTaP-IPV vaccine.95% CI: [-0.32, 4.08]
Primary
Number of Subjects With Booster Responses to Diphteria and Tetanus
Anti-diphteria (anti-D) and anti-tetanus (anti-T) booster response was defined as: * initially seronegative subjects (sero-) (pre-booster antibody concentration below cut-off of \< 0.1 international units per milliliter (IU/mL)) with an increase of at least four times the cut-off one month after vaccination (post-booster antibody concentration ≥0.4 IU/mL) * initially seropositive subjects (sero+) (pre-booster antibody concentration ≥0.1 IU/mL) with an increase of at least four times the pre-booster antibody concentration one month after vaccination
Time frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Population: Analysis was performed on the according-to-protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Kinrix + M-M-R II + Varivax | Number of Subjects With Booster Responses to Diphteria and Tetanus | Anti-D | 209 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects With Booster Responses to Diphteria and Tetanus | Anti-T | 208 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Booster Responses to Diphteria and Tetanus | Anti-T | 203 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Booster Responses to Diphteria and Tetanus | Anti-D | 207 Participants |
Comparison: To demonstrate the non-inferiority of DTaP-IPV vaccine co-administered with Varicella and MMR vaccines compared to DTaP-IPV vaccine co-administered with MMR only in terms of diphtheria (D) booster response one month after vaccination with DTaP-IPV vaccine.95% CI: [-2.54, 2.58]
Comparison: To demonstrate the non-inferiority of DTaP-IPV vaccine co-administered with Varicella and MMR vaccines compared to DTaP-IPV vaccine co-administered with MMR only in terms of tetanus (T) booster response one month after vaccination with DTaP-IPV vaccine.95% CI: [-1.99, 4.26]
Secondary
Geometric Mean Concentrations (GMCs) for Anti-D and Anti-T Antibodies
Concentrations were expressed as GMCs in IU/mL.
Time frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Population: Analysis was performed on the according-to-protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Kinrix + M-M-R II + Varivax | Geometric Mean Concentrations (GMCs) for Anti-D and Anti-T Antibodies | Anti-D | 14.273 IU/mL |
| Kinrix + M-M-R II + Varivax | Geometric Mean Concentrations (GMCs) for Anti-D and Anti-T Antibodies | Anti-T | 8.658 IU/mL |
| Kinrix + M-M-R II -> Varivax | Geometric Mean Concentrations (GMCs) for Anti-D and Anti-T Antibodies | Anti-T | 8.138 IU/mL |
| Kinrix + M-M-R II -> Varivax | Geometric Mean Concentrations (GMCs) for Anti-D and Anti-T Antibodies | Anti-D | 14.809 IU/mL |
Secondary
GMCs for Anti-PT, Anti-FHA, Anti-PRN Antibodies
Concentrations are expressed as GMCs in Enzyme-Linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).
Time frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Population: Analysis was performed on the according-to-protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Kinrix + M-M-R II + Varivax | GMCs for Anti-PT, Anti-FHA, Anti-PRN Antibodies | Anti-PT | 96.5 EL.U/mL |
| Kinrix + M-M-R II + Varivax | GMCs for Anti-PT, Anti-FHA, Anti-PRN Antibodies | Anti-FHA | 968.9 EL.U/mL |
| Kinrix + M-M-R II + Varivax | GMCs for Anti-PT, Anti-FHA, Anti-PRN Antibodies | Anti-PRN | 627.1 EL.U/mL |
| Kinrix + M-M-R II -> Varivax | GMCs for Anti-PT, Anti-FHA, Anti-PRN Antibodies | Anti-PT | 101.3 EL.U/mL |
| Kinrix + M-M-R II -> Varivax | GMCs for Anti-PT, Anti-FHA, Anti-PRN Antibodies | Anti-FHA | 968.2 EL.U/mL |
| Kinrix + M-M-R II -> Varivax | GMCs for Anti-PT, Anti-FHA, Anti-PRN Antibodies | Anti-PRN | 620.4 EL.U/mL |
Secondary
Number of Subjects Protected Against Poliovirus 1, 2 and 3
Seroprotection was defined: \* anti-poliovirus type 1, 2 or 3 antibody titer greater than or equal to 8 ED50. ED50 is defined here as the reverse of the dilution resulting in 50% inhibition.
Time frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Population: Analysis was performed on the according-to-protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Kinrix + M-M-R II + Varivax | Number of Subjects Protected Against Poliovirus 1, 2 and 3 | Anti-Polio 1 | 219 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects Protected Against Poliovirus 1, 2 and 3 | Anti-Polio 2 | 218 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects Protected Against Poliovirus 1, 2 and 3 | Anti-Polio 3 | 219 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects Protected Against Poliovirus 1, 2 and 3 | Anti-Polio 1 | 211 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects Protected Against Poliovirus 1, 2 and 3 | Anti-Polio 2 | 212 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects Protected Against Poliovirus 1, 2 and 3 | Anti-Polio 3 | 212 Participants |
Secondary
Number of Subjects Seropositive for Anti-PT, Anti-FHA and Anti-PRN Antibodies
Seropositivity was defined as a concentration greater than or equal to 5.0 EL.U/mL
Time frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Population: Analysis was performed on the according-to-protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Kinrix + M-M-R II + Varivax | Number of Subjects Seropositive for Anti-PT, Anti-FHA and Anti-PRN Antibodies | anti-PT | 220 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects Seropositive for Anti-PT, Anti-FHA and Anti-PRN Antibodies | anti-FHA | 220 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects Seropositive for Anti-PT, Anti-FHA and Anti-PRN Antibodies | anti-PRN | 220 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects Seropositive for Anti-PT, Anti-FHA and Anti-PRN Antibodies | anti-PT | 212 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects Seropositive for Anti-PT, Anti-FHA and Anti-PRN Antibodies | anti-FHA | 212 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects Seropositive for Anti-PT, Anti-FHA and Anti-PRN Antibodies | anti-PRN | 212 Participants |
Secondary
Number of Subjects Seroprotected Against Diphteria and Tetanus
Seroprotection status was defined as: * anti-D antibody concentration greater than or equal to 0.1 IU/mL * anti-T antibody concentration greater than or equal to 0.1 IU/mL
Time frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Population: Analysis was performed on the according-to-protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Kinrix + M-M-R II + Varivax | Number of Subjects Seroprotected Against Diphteria and Tetanus | Anti-D | 217 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects Seroprotected Against Diphteria and Tetanus | Anti-T | 217 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects Seroprotected Against Diphteria and Tetanus | Anti-D | 212 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects Seroprotected Against Diphteria and Tetanus | Anti-T | 212 Participants |
Secondary
Number of Subjects With an Anti-polio 1, 2, 3 Booster Response
Anti-poliovirus 1, anti-poliovirus 2 and anti-poliovirus 3 booster response: * initially seronegative subjects (pre-booster antibody titer below cut-off of 8 ED50) with an antibody titer ≥ 32 ED50 one month after vaccination * initially seropositive subjects (pre-booster antibody titers ≥ 8 ED50) with an increase at least four times the pre-booster antibody titer one month after vaccination. ED50 is defined here as the reverse of the dilution resulting in 50% inhibition. The lowest dilution at which serum samples were tested is 1:8 from which a test was considered positive.
Time frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Population: Analysis was performed on the according-to-protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Kinrix + M-M-R II + Varivax | Number of Subjects With an Anti-polio 1, 2, 3 Booster Response | Anti-polio 1 | 211 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects With an Anti-polio 1, 2, 3 Booster Response | Anti-polio 2 | 204 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects With an Anti-polio 1, 2, 3 Booster Response | Anti-polio 3 | 213 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With an Anti-polio 1, 2, 3 Booster Response | Anti-polio 3 | 207 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With an Anti-polio 1, 2, 3 Booster Response | Anti-polio 1 | 202 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With an Anti-polio 1, 2, 3 Booster Response | Anti-polio 2 | 207 Participants |
Secondary
Number of Subjects With Anti-D and Anti-T Antibody Concentrations Above Cut-off Value
Cut-off value was defined as greater than or equal to 1.0 international units per milliliter (IU/mL).
Time frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Population: Analysis was performed on the according-to-protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Kinrix + M-M-R II + Varivax | Number of Subjects With Anti-D and Anti-T Antibody Concentrations Above Cut-off Value | Anti-D | 217 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects With Anti-D and Anti-T Antibody Concentrations Above Cut-off Value | Anti-T | 217 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Anti-D and Anti-T Antibody Concentrations Above Cut-off Value | Anti-D | 212 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Anti-D and Anti-T Antibody Concentrations Above Cut-off Value | Anti-T | 209 Participants |
Secondary
Number of Subjects With Any Solicited General Symptoms
Solicited general symptoms included fever \[temperature equal to or greater than 37.5 degrees Celsius (°C)\], drowsiness and loss of appetite. Any was defined as incidence of a particular symptom regardless of intensity grade.
Time frame: Within 4 days (Day 0 to 3) after booster immunization * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax
Population: The analysis was performed on the total vaccinated cohort, which included subjects with at least one vaccine administration documented, only on subjects with their symptom sheets completed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Kinrix + M-M-R II + Varivax | Number of Subjects With Any Solicited General Symptoms | Any Drowsiness | 61 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects With Any Solicited General Symptoms | Any Loss of appetite | 60 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects With Any Solicited General Symptoms | Any Temperature (Axillary) | 58 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Any Solicited General Symptoms | Any Drowsiness | 66 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Any Solicited General Symptoms | Any Loss of appetite | 57 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Any Solicited General Symptoms | Any Temperature (Axillary) | 68 Participants |
Secondary
Number of Subjects With Any Solicited Local Symptoms
Solicited local symptoms included pain, redness and swelling at the injection site. Any was defined as incidence of a particular symptom regardless of intensity grade.
Time frame: Within 4 days (Day 0 to 3) after booster immunization * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax
Population: The analysis was performed on the total vaccinated cohort, which included subjects with at least one vaccine administration documented, only on subjects with their symptom sheets completed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Kinrix + M-M-R II + Varivax | Number of Subjects With Any Solicited Local Symptoms | Any Pain | 156 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects With Any Solicited Local Symptoms | Any Redness | 115 Participants |
| Kinrix + M-M-R II + Varivax | Number of Subjects With Any Solicited Local Symptoms | Any Swelling | 95 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Any Solicited Local Symptoms | Any Swelling | 84 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Any Solicited Local Symptoms | Any Pain | 166 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Any Solicited Local Symptoms | Any Redness | 114 Participants |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events are medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: During the entire study period (from Day 0 to 6 months post-vaccination)
Population: Analysis was performed on the total vaccinated cohort, which included all subjects with at least one vaccine administration documented and for whom data was available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Kinrix + M-M-R II + Varivax | Number of Subjects With Serious Adverse Events (SAEs) | 0 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Serious Adverse Events (SAEs) | 1 Participants |
Secondary
Number of Subjects With Unsolicited Adverse Events
An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event.
Time frame: Up to 31 days (Day 0 through Day 30) after booster vaccination * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax
Population: Analysis was performed on the total vaccinated cohort, which included all subjects with at least one vaccine administration documented and for whom data was available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Kinrix + M-M-R II + Varivax | Number of Subjects With Unsolicited Adverse Events | 75 Participants |
| Kinrix + M-M-R II -> Varivax | Number of Subjects With Unsolicited Adverse Events | 72 Participants |