Varicella
Conditions
Brief summary
This study will evaluate the immunogenicity, safety, and tolerability of VARIVAX® (Varicella Virus Vaccine Live) manufactured with a new passage extension (PE34) process compared with the VARIVAX® 2016 commercial process. The primary hypotheses being tested are that antibody response rate and mean antibody titer induced at 6 weeks after a single vaccination by VARIVAX® PE34 Process are non-inferior to those induced by VARIVAX® 2016 commercial process, and that antibody response rate induced by VARIVAX® PE34 Process is acceptable.
Interventions
BIOLOGICALVARIVAX® PE34 Process
Varicella virus vaccine live manufactured with a new passage extension process (PE34)
BIOLOGICALVARIVAX® 2016 Commercial Process
Varicella virus vaccine live manufactured with the 2016 commercial process
BIOLOGICALM-M-R II®
Measles, Mumps, and Rubella virus vaccine live
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Months to 23 Months
Healthy volunteers
Yes
Inclusion criteria
* Negative clinical history for varicella, herpes zoster, measles, mumps, and rubella
Exclusion criteria
* Received any measles, mumps, rubella, or varicella vaccine at any time prior to the study, or is anticipated to receive any of these vaccines outside the study * Any congenital or acquired immune deficiency, neoplastic disease, or depressed immunity * Received systemic immunomodulatory steroids within 3 months prior to entering the study or is expected to receive them during the course of the study * History of allergy or anaphylactic reaction to neomycin, gelatin, sorbitol, egg proteins, chicken proteins, or any component of VARIVAX® or M-M-R II® * Has any blood dyscrasias, leukemia, lymphoma, or other malignant neoplasm affecting the bone marrow or lymphatic systems * Received salicylates within 14 days prior to study vaccination * Exposed to varicella, herpes zoster, measles, mumps, or rubella in the 4 weeks prior to study vaccination * Received immune globulin, a blood transfusion, or blood-derived products within 5 months prior to study vaccination * History of seizure disorder, including febrile seizure * Fever illness (\>=102.2 °F \[39.0 °C\] within 72 hours prior to study vaccination * History of thrombocytopenia * Born to a human immunodeficiency virus (HIV)-infected mother * Has a diagnosis of active untreated tuberculosis * Participated in any other clinical trial (other than a surveillance study) within 30 days prior to study enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Varicella Zoster Virus Antibody Levels ≥5 Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Units/mL | 6 weeks (43 days) after vaccination 1 | The varicella zoster virus (VZV) antibody response rate was defined as the percentage of participants with VZV antibody titer ≥5 glycoprotein enzyme-linked immunosorbent assay (gpELISA) units/mL among participants who were seronegative to VZV (titers \<1.25 gpELISA units/mL) at baseline. |
| Geometric Mean Titer of VZV Antibodies | 6 weeks (43 days) after vaccination 1 | The geometric mean titer (GMT) of VZV antibodies after vaccination 1 was assessed. Antibody titers were measured with gpELISA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 2 (Incidence > 0%) | Up to 42 days after vaccination 2 | The percentage of participants with measles-like, rubella-like, varicella-like, zoster-like rash, and mumps-like symptoms after vaccination 2 was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding. |
| Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, or Injection-site Pain/Tenderness After Vaccination 1 | Up to 5 days after vaccination 1 | The percentage of participants with solicited (on a Vaccine Report Card) injection-site erythema, injection-site swelling, or injection-site pain/tenderness was assessed. |
| Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 2 | Up to 5 days after vaccination 2 | The percentage of participants with solicited (Vaccine Report Card) injection-site erythema, injection-site swelling, and injection-site pain/tenderness was assessed. |
| Percentage of Participants With One or More Adverse Events | Up to 42 days after vaccination 1 and up to 42 days after vaccination 2 | An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants with one or more adverse events for Day 1 through Day 42 after vaccination 1 and Day 1 through Day 42 after vaccination 2 was reported. |
| Percentage of Participants With One or More Serious Adverse Events | Up to ~180 days after vaccination 2 (Up to ~285 days) | A serious adverse event (SAE) is defined as an adverse event that resulted in death, was life threatening, resulted in persistent or significant disability or incapacity, resulted in or prolonged a hospitalization, is a congenital anomaly or birth defect, is a cancer, was an overdose, or was an important medical event based on appropriate medical judgment. The percentage of participants with one or more SAEs \ 180 days after vaccination 2 was reported. |
| Percentage of Participants With One or More Vaccine-Related Adverse Events | Up to 42 days after vaccination 1 and up to 42 days after vaccination 2 | The percentage of participants with one or more vaccine-related adverse events for Day 1 through Day 42 after vaccination 1 and Day 1 through Day 42 after vaccination 2 was reported. |
| Percentage of Participants With One or More Systemic Adverse Events After Vaccination 1 (Incidence ≥ 4) | Up to 42 days after vaccination 1 | All systemic adverse events were recorded on an electronic vaccination report card (eVRC) for Day 1 through Day 42 after vaccination 1. The percentage of participants with one or more systemic adverse events (incidence ≥4 participants in one or more of the vaccination groups) was reported. |
| Percentage of Participants With One or More Systemic Adverse Events After Vaccination 2 (Incidence > 0) | Up to 42 days after vaccination 2 | All systemic adverse events were recorded on an electronic vaccination report card (eVRC) for Day 1 through Day 42 after vaccination 2. The percentage of participants with one or more systemic adverse events was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding. |
| Percentage of Participants With Fever (≥102.2 °F Oral Equivalent) | Up to 42 days after vaccination 1; Up to 42 days after vaccination 2 | The percentage of participants with fever ≥102.2 °F oral equivalent for Day 1 through Day 42 after vaccination 1 and Day 1 through Day 42 after vaccination 2 was reported. |
| Geometric Mean Fold Rise From Baseline in Varicella Zoster Virus Antibody Titer in Participants Initially Seropositive to Varicella Zoster Virus Antibody | Baseline and 6 weeks (~43 days) after vaccination 1 | Blood samples were taken at pre-vaccination (baseline) and approximately 43 days after vaccination 1 to determine the geometric mean titer (GMT) of VZV antibodies via gpELISA. The geometric mean fold rise (GMFR) was calculated as GMT post vaccination 1/GMT pre-vaccination (baseline). Confidence interval is calculated if there are at least 5 subjects who are seropositive. |
| Percentage of Participants With a ≥4-fold Rise From Baseline in Varicella Zoster Virus Antibody Titers in Participants Initially Seropositive to Varicella Zoster Virus Antibody | Baseline and 6 weeks (~43 days) after vaccination 1 | The percentage of participants with a geometric mean ≥4-fold rise from baseline of ≥1.25gpELISA units/mL in VZV antibody titer at approximately 43 days after vaccination 1 was assessed. |
| Percentage of Participants With One or More Vaccine-Related Serious Adverse Events | Up to ~180 days after vaccination 2 | The percentage of participants with one or more vaccine-related serious adverse events up to \ 180 days after vaccination 2 was reported. The study investigator determines whether the serious adverse event is related to the vaccine. |
| Percentage of Participants Who Discontinued From the Study Due to an Adverse Event | Up to 42 days after vaccination 1 and up to 42 days after vaccination 2 | The percentage of participants discontinued from the study due to an adverse event for Day 1 through Day 42 after vaccination 1 and Day 1 through Day 42 after vaccination 2 was reported. |
| Percentage of Participants With One or More Unsolicited Injection-Site Adverse Events After Vaccination 1 (Incidence > 0%) | Up to 42 days after vaccination 1 | The percentage of participants with unsolicited injection-site adverse events (or AEs not superficially listed on eVRC) for Day 1 through Day 42 after vaccination 1 was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding. |
| Percentage of Participants With One or More Unsolicited Injection-Site Adverse Events After Vaccination 2 (Incidence > 0%) | Up to 42 days after vaccination 2 | The percentage of participants with unsolicited injection-site adverse events (or AEs not superficially listed on eVRC) for Day 1 through Day 42 after vaccination 2 was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding. |
| Percentage of Participants With Medically-Attended Adverse Events (Incidence ≥5%) | Up to ~180 days after vaccination 2 (Up to ~285 days) | The percentage of participants with medically-attended AEs up to \ 180 days after vaccination 2 that did not meet the definition of serious adverse event (incidence ≥5% in one or more vaccination groups) was reported. |
| Percentage of Participants With Immunogenicity to Varicella Zoster Virus in Participants Initially Seropositive to Varicella Zoster Virus Antibody (≥ 5gpELISA Units/mL) | 6 weeks (~43 days) after vaccination 1 | The percentage of participants with seropositive antibody titer (≥1.25gpELISA units/mL) at baseline and postvaccination serology contributing to the per-protocol analysis was assessed. Confidence interval is calculated if there are at least 5 subjects who are seropositive. Antibody titers were assessed using gpELISA. |
| Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 1 (Incidence > 0%) | Up to 42 days after vaccination 1 | The percentage of participants with measles-like, rubella-like, varicella-like, zoster-like rash, and mumps-like symptoms after vaccination 1 was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VARIVAX PE34 + M-M-R II VARIVAX® Passage Extension 34 (PE34) Process 0.5 mL administered in the left arm or thigh and M-M-R®II vaccine 0.5 mL administered in the right arm or thigh by subcutaneous injection on Day 1 and Day 91. | 300 |
| VARIVAX (2016 CP) + M-M-R II 2016 Commercial Process vaccine 0.5 mL administered in the left arm or thigh and M-M-R® II vaccine 0.5 mL administered in the right arm or thigh by subcutaneous injection on Day 1 and Day 91. | 300 |
| Total | 600 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Contraindication to study medication | 1 | 0 |
| Overall Study | Lost to Follow-up | 15 | 16 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Parent/Guardian | 12 | 11 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | VARIVAX (2016 CP) + M-M-R II | Total | VARIVAX PE34 + M-M-R II |
|---|---|---|---|
| Age, Continuous | 13.2 Months STANDARD_DEVIATION 1.7 | 13.1 Months STANDARD_DEVIATION 1.6 | 13.0 Months STANDARD_DEVIATION 1.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 60 Participants | 106 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 237 Participants | 491 Participants | 254 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 58 Participants | 35 Participants |
| Race (NIH/OMB) More than one race | 31 Participants | 54 Participants | 23 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 239 Participants | 476 Participants | 237 Participants |
| Sex: Female, Male Female | 127 Participants | 280 Participants | 153 Participants |
| Sex: Female, Male Male | 173 Participants | 320 Participants | 147 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 299 | 0 / 300 |
| other Total, other adverse events | 255 / 299 | 240 / 300 |
| serious Total, serious adverse events | 6 / 299 | 6 / 300 |
Outcome results
Primary
Geometric Mean Titer of VZV Antibodies
The geometric mean titer (GMT) of VZV antibodies after vaccination 1 was assessed. Antibody titers were measured with gpELISA.
Time frame: 6 weeks (43 days) after vaccination 1
Population: The analysis population included the number of participants with seronegative antibody titer (\<1.25 gpELISA units/mL) at baseline and postvaccination serology.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Geometric Mean Titer of VZV Antibodies | 18.5 gpELISA units/mL |
| VARIVAX (2016 CP) + M-M-R II | Geometric Mean Titer of VZV Antibodies | 19.0 gpELISA units/mL |
p-value: <0.00195% CI: [0.9, 1.1]Miettinen and Nurminen
Primary
Percentage of Participants With Varicella Zoster Virus Antibody Levels ≥5 Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Units/mL
The varicella zoster virus (VZV) antibody response rate was defined as the percentage of participants with VZV antibody titer ≥5 glycoprotein enzyme-linked immunosorbent assay (gpELISA) units/mL among participants who were seronegative to VZV (titers \<1.25 gpELISA units/mL) at baseline.
Time frame: 6 weeks (43 days) after vaccination 1
Population: The analysis population included the number of participants with seronegative antibody titer (\<1.25 gpELISA units/mL) at baseline and postvaccination serology.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Varicella Zoster Virus Antibody Levels ≥5 Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Units/mL | 98.4 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Varicella Zoster Virus Antibody Levels ≥5 Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Units/mL | 98.3 Percentage of Participants |
p-value: <0.00195% CI: [-2.7, 2.8]Miettinen and Nurminen
Comparison: The conclusion of acceptability is based on the lower bound of the 95% Confidence Interval (CI) being \>76%, and implies that the value of the parameter is statistically significantly greater than the prespecified acceptability criterion (76%).p-value: <0.00195% CI: [95.9, 99.6]Exact CI method/binomial proportion
Secondary
Geometric Mean Fold Rise From Baseline in Varicella Zoster Virus Antibody Titer in Participants Initially Seropositive to Varicella Zoster Virus Antibody
Blood samples were taken at pre-vaccination (baseline) and approximately 43 days after vaccination 1 to determine the geometric mean titer (GMT) of VZV antibodies via gpELISA. The geometric mean fold rise (GMFR) was calculated as GMT post vaccination 1/GMT pre-vaccination (baseline). Confidence interval is calculated if there are at least 5 subjects who are seropositive.
Time frame: Baseline and 6 weeks (~43 days) after vaccination 1
Population: The analysis population consisted of all participants with with seropositive antibody titer (≥1.25gpELISA units/mL) at baseline and with available postvaccination serology data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Geometric Mean Fold Rise From Baseline in Varicella Zoster Virus Antibody Titer in Participants Initially Seropositive to Varicella Zoster Virus Antibody | 6.5 Ratio |
| VARIVAX (2016 CP) + M-M-R II | Geometric Mean Fold Rise From Baseline in Varicella Zoster Virus Antibody Titer in Participants Initially Seropositive to Varicella Zoster Virus Antibody | 7.2 Ratio |
Secondary
Percentage of Participants Who Discontinued From the Study Due to an Adverse Event
The percentage of participants discontinued from the study due to an adverse event for Day 1 through Day 42 after vaccination 1 and Day 1 through Day 42 after vaccination 2 was reported.
Time frame: Up to 42 days after vaccination 1 and up to 42 days after vaccination 2
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with data at the time of assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants Who Discontinued From the Study Due to an Adverse Event | 0.0 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants Who Discontinued From the Study Due to an Adverse Event | 0.0 Percentage of Participants |
95% CI: [-1.3, 1.3]
Secondary
Percentage of Participants With a ≥4-fold Rise From Baseline in Varicella Zoster Virus Antibody Titers in Participants Initially Seropositive to Varicella Zoster Virus Antibody
The percentage of participants with a geometric mean ≥4-fold rise from baseline of ≥1.25gpELISA units/mL in VZV antibody titer at approximately 43 days after vaccination 1 was assessed.
Time frame: Baseline and 6 weeks (~43 days) after vaccination 1
Population: The analysis population consisted of all participants with seropositive antibody titer (≥1.25gpELISA units/mL) and available postvaccination serology data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With a ≥4-fold Rise From Baseline in Varicella Zoster Virus Antibody Titers in Participants Initially Seropositive to Varicella Zoster Virus Antibody | 80.6 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With a ≥4-fold Rise From Baseline in Varicella Zoster Virus Antibody Titers in Participants Initially Seropositive to Varicella Zoster Virus Antibody | 82.5 Percentage of Participants |
Secondary
Percentage of Participants With Fever (≥102.2 °F Oral Equivalent)
The percentage of participants with fever ≥102.2 °F oral equivalent for Day 1 through Day 42 after vaccination 1 and Day 1 through Day 42 after vaccination 2 was reported.
Time frame: Up to 42 days after vaccination 1; Up to 42 days after vaccination 2
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with temperature data at the time of assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Fever (≥102.2 °F Oral Equivalent) | Up to 42 days after Vaccination 1 | 11.8 Percentage of Participants |
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Fever (≥102.2 °F Oral Equivalent) | Up to 42 days after Vaccination 2 | 8.9 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Fever (≥102.2 °F Oral Equivalent) | Up to 42 days after Vaccination 2 | 6.1 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Fever (≥102.2 °F Oral Equivalent) | Up to 42 days after Vaccination 1 | 9.8 Percentage of Participants |
Comparison: Up to 42 days after Vaccination 1p-value: 0.43695% CI: [-3.1, 7.1]Miettinen & Nurminen
Comparison: Up to 42 days after Vaccination 2p-value: 0.20495% CI: [-1.6, 7.5]Miettinen & Nurminen
Secondary
Percentage of Participants With Immunogenicity to Varicella Zoster Virus in Participants Initially Seropositive to Varicella Zoster Virus Antibody (≥ 5gpELISA Units/mL)
The percentage of participants with seropositive antibody titer (≥1.25gpELISA units/mL) at baseline and postvaccination serology contributing to the per-protocol analysis was assessed. Confidence interval is calculated if there are at least 5 subjects who are seropositive. Antibody titers were assessed using gpELISA.
Time frame: 6 weeks (~43 days) after vaccination 1
Population: The analysis population consisted of all participants with seropositive antibody titer (≥1.25gpELISA units/mL) at baseline and with available postvaccination serology data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Immunogenicity to Varicella Zoster Virus in Participants Initially Seropositive to Varicella Zoster Virus Antibody (≥ 5gpELISA Units/mL) | 100.0 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Immunogenicity to Varicella Zoster Virus in Participants Initially Seropositive to Varicella Zoster Virus Antibody (≥ 5gpELISA Units/mL) | 97.5 Percentage of Participants |
Secondary
Percentage of Participants With Medically-Attended Adverse Events (Incidence ≥5%)
The percentage of participants with medically-attended AEs up to \ 180 days after vaccination 2 that did not meet the definition of serious adverse event (incidence ≥5% in one or more vaccination groups) was reported.
Time frame: Up to ~180 days after vaccination 2 (Up to ~285 days)
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with data at the time of assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Medically-Attended Adverse Events (Incidence ≥5%) | 29.5 Percentge of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Medically-Attended Adverse Events (Incidence ≥5%) | 26.6 Percentge of Participants |
95% CI: [-4.6, 10.3]
Secondary
Percentage of Participants With One or More Adverse Events
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants with one or more adverse events for Day 1 through Day 42 after vaccination 1 and Day 1 through Day 42 after vaccination 2 was reported.
Time frame: Up to 42 days after vaccination 1 and up to 42 days after vaccination 2
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with data at the time of assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With One or More Adverse Events | 90.0 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With One or More Adverse Events | 88.3 Percentage of Participants |
95% CI: [-3.4, 6.7]
Secondary
Percentage of Participants With One or More Serious Adverse Events
A serious adverse event (SAE) is defined as an adverse event that resulted in death, was life threatening, resulted in persistent or significant disability or incapacity, resulted in or prolonged a hospitalization, is a congenital anomaly or birth defect, is a cancer, was an overdose, or was an important medical event based on appropriate medical judgment. The percentage of participants with one or more SAEs \ 180 days after vaccination 2 was reported.
Time frame: Up to ~180 days after vaccination 2 (Up to ~285 days)
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with data at the time of assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With One or More Serious Adverse Events | 2.0 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With One or More Serious Adverse Events | 2.0 Percentage of Participants |
95% CI: [-2.5, 2.6]
Secondary
Percentage of Participants With One or More Systemic Adverse Events After Vaccination 1 (Incidence ≥ 4)
All systemic adverse events were recorded on an electronic vaccination report card (eVRC) for Day 1 through Day 42 after vaccination 1. The percentage of participants with one or more systemic adverse events (incidence ≥4 participants in one or more of the vaccination groups) was reported.
Time frame: Up to 42 days after vaccination 1
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with data at the time of assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With One or More Systemic Adverse Events After Vaccination 1 (Incidence ≥ 4) | 76.6 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With One or More Systemic Adverse Events After Vaccination 1 (Incidence ≥ 4) | 74.3 Percentage of Participants |
95% CI: [-4.7, 9.2]
Secondary
Percentage of Participants With One or More Systemic Adverse Events After Vaccination 2 (Incidence > 0)
All systemic adverse events were recorded on an electronic vaccination report card (eVRC) for Day 1 through Day 42 after vaccination 2. The percentage of participants with one or more systemic adverse events was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding.
Time frame: Up to 42 days after vaccination 2
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with data at the time of assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With One or More Systemic Adverse Events After Vaccination 2 (Incidence > 0) | 60.9 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With One or More Systemic Adverse Events After Vaccination 2 (Incidence > 0) | 59.9 Percentage of Participants |
Secondary
Percentage of Participants With One or More Unsolicited Injection-Site Adverse Events After Vaccination 1 (Incidence > 0%)
The percentage of participants with unsolicited injection-site adverse events (or AEs not superficially listed on eVRC) for Day 1 through Day 42 after vaccination 1 was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding.
Time frame: Up to 42 days after vaccination 1
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with data at the time of assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With One or More Unsolicited Injection-Site Adverse Events After Vaccination 1 (Incidence > 0%) | 8.0 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With One or More Unsolicited Injection-Site Adverse Events After Vaccination 1 (Incidence > 0%) | 9.3 Percentage of Participants |
Secondary
Percentage of Participants With One or More Unsolicited Injection-Site Adverse Events After Vaccination 2 (Incidence > 0%)
The percentage of participants with unsolicited injection-site adverse events (or AEs not superficially listed on eVRC) for Day 1 through Day 42 after vaccination 2 was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding.
Time frame: Up to 42 days after vaccination 2
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with data at the time of assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With One or More Unsolicited Injection-Site Adverse Events After Vaccination 2 (Incidence > 0%) | 1.4 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With One or More Unsolicited Injection-Site Adverse Events After Vaccination 2 (Incidence > 0%) | 2.1 Percentage of Participants |
Secondary
Percentage of Participants With One or More Vaccine-Related Adverse Events
The percentage of participants with one or more vaccine-related adverse events for Day 1 through Day 42 after vaccination 1 and Day 1 through Day 42 after vaccination 2 was reported.
Time frame: Up to 42 days after vaccination 1 and up to 42 days after vaccination 2
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with data at the time of assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With One or More Vaccine-Related Adverse Events | 56.2 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With One or More Vaccine-Related Adverse Events | 54.3 Percentage of Participants |
95% CI: [-6.1, 9.8]
Secondary
Percentage of Participants With One or More Vaccine-Related Serious Adverse Events
The percentage of participants with one or more vaccine-related serious adverse events up to \ 180 days after vaccination 2 was reported. The study investigator determines whether the serious adverse event is related to the vaccine.
Time frame: Up to ~180 days after vaccination 2
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with data at the time of assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With One or More Vaccine-Related Serious Adverse Events | 0.0 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With One or More Vaccine-Related Serious Adverse Events | 0.0 Percentage of Participants |
95% CI: [-1.3, 1.3]
Secondary
Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 2
The percentage of participants with solicited (Vaccine Report Card) injection-site erythema, injection-site swelling, and injection-site pain/tenderness was assessed.
Time frame: Up to 5 days after vaccination 2
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with data at the time of assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 2 | Injection site erythema | 19.6 Percentage of Participants |
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 2 | Injection site pain | 8.7 Percentage of Participants |
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 2 | Injection site swelling | 10.1 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 2 | Injection site erythema | 19.9 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 2 | Injection site pain | 10.3 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 2 | Injection site swelling | 8.2 Percentage of Participants |
Comparison: Injection site erythemap-value: 0.93195% CI: [-6.9, 6.4]Miettinen & Nurminen
Comparison: Injection site painp-value: 0.52395% CI: [-6.6, 3.4]Miettinen & Nurminen
Comparison: Injection site swellingp-value: 0.41595% CI: [-2.9, 6.9]Miettinen & Nurminen
Secondary
Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, or Injection-site Pain/Tenderness After Vaccination 1
The percentage of participants with solicited (on a Vaccine Report Card) injection-site erythema, injection-site swelling, or injection-site pain/tenderness was assessed.
Time frame: Up to 5 days after vaccination 1
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with data at the time of assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, or Injection-site Pain/Tenderness After Vaccination 1 | Injection site erythema | 9.7 Percentage of Participants |
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, or Injection-site Pain/Tenderness After Vaccination 1 | Injection site pain | 13.4 Percentage of Participants |
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, or Injection-site Pain/Tenderness After Vaccination 1 | Injection site swelling | 3.0 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, or Injection-site Pain/Tenderness After Vaccination 1 | Injection site erythema | 10.7 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, or Injection-site Pain/Tenderness After Vaccination 1 | Injection site pain | 12.7 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, or Injection-site Pain/Tenderness After Vaccination 1 | Injection site swelling | 5.7 Percentage of Participants |
Comparison: Injection site erythemap-value: 0.69695% CI: [-5.9, 4]Miettinen & Nurminen
Comparison: Injection site painp-value: 0.79695% CI: [-4.7, 6.2]Miettinen & Nurminen
Comparison: Injection site swellingp-value: 0.11195% CI: [-6.2, 0.7]Miettinen & Nurminen
Secondary
Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 1 (Incidence > 0%)
The percentage of participants with measles-like, rubella-like, varicella-like, zoster-like rash, and mumps-like symptoms after vaccination 1 was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding.
Time frame: Up to 42 days after vaccination 1
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with data at the time of assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 1 (Incidence > 0%) | Measles-like rash | 0.3 Percentage of Participants |
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 1 (Incidence > 0%) | Rubella-like rash | 0.3 Percentage of Participants |
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 1 (Incidence > 0%) | Varicella-like rash | 2.7 Percentage of Participants |
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 1 (Incidence > 0%) | Zoster-like rash | 0.0 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 1 (Incidence > 0%) | Zoster-like rash | 0.3 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 1 (Incidence > 0%) | Measles-like rash | 1.7 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 1 (Incidence > 0%) | Varicella-like rash | 1.3 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 1 (Incidence > 0%) | Rubella-like rash | 0.0 Percentage of Participants |
Comparison: Measles-like rashp-value: 0.10295% CI: [-3.5, 0.4]Miettinen & Nurminen
Comparison: Rubella-like rashp-value: 0.31795% CI: [-0.9, 1.9]Miettinen & Nurminen
Comparison: Varicella-like rashp-value: 0.24195% CI: [-1, 4]Miettinen & Nurminen
Comparison: Zoster-like rashp-value: 0.31895% CI: [-1.9, 0.9]Miettinen & Nurminen
Secondary
Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 2 (Incidence > 0%)
The percentage of participants with measles-like, rubella-like, varicella-like, zoster-like rash, and mumps-like symptoms after vaccination 2 was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding.
Time frame: Up to 42 days after vaccination 2
Population: The analysis population consisted of all randomized/allocated participants who received at least 1 vaccination of study treatment with data at the time of assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 2 (Incidence > 0%) | Varicella-like rash | 0.4 Percentage of Participants |
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 2 (Incidence > 0%) | Zoster-like rash | 0.4 Percentage of Participants |
| VARIVAX PE34 + M-M-R II | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 2 (Incidence > 0%) | Measles-like rash | 1.4 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 2 (Incidence > 0%) | Varicella-like rash | 0.7 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 2 (Incidence > 0%) | Zoster-like rash | 0.0 Percentage of Participants |
| VARIVAX (2016 CP) + M-M-R II | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 2 (Incidence > 0%) | Measles-like rash | 0.4 Percentage of Participants |
Comparison: Measles-like rashp-value: 0.1795% CI: [-0.7, 3.4]Miettinen & Nurminen
Comparison: Varicella-like rashp-value: 0.57695% CI: [-2.2, 1.4]Miettinen & Nurminen
Comparison: Zoster-like rashp-value: 0.31295% CI: [-1, 2]Miettinen & Nurminen