Varicella
Conditions
Brief summary
This study will evaluate the immunogenicity, safety, and tolerability of VARIVAX™ (Varicella Virus Vaccine Live) manufactured with a New Seed Process (NSP) compared with the VARIVAX™ 2007 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™ NSP are non-inferior to those induced by VARIVAX™ 2007 process, and that antibody response rate induced by VARIVAX™ NSP is acceptable.
Interventions
BIOLOGICALVARIVAX™ New Seed Process
Varicella virus vaccine live manufactured with a new seed process
BIOLOGICALVARIVAX™ 2007 process
Varicella virus vaccine live manufactured with the 2007 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™ * 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 * 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 (VZV) Antibody Levels >=5 Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Units/mL | 6 weeks (43 days) after vaccination 1 | — |
| Geometric Mean Titer of VZV Antibodies | 6 weeks (43 days) after vaccination 1 | Antibody titers were measured with gpELISA. |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 2 | Up to 42 days after Vaccination 2 |
| Percentage of Participants With Fever (>=102.2 °F Oral Equivalent) | Up to 42 days after Vaccination 1 and Vaccination 2 (up to 133 days) |
| 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 |
| Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 1 | Up to 5 days after Vaccination 1 |
| Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 1 | Up to 42 days after Vaccination 1 |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VARIVAX™ New Seed Process + M-M-R II™ VARIVAX™ New Seed Process 0.5 mL administered in the left arm and M-M-R II™ vaccine 0.5 mL administered in the right arm by subcutaneous injection on Day 1 and Day 91. | 306 |
| VARIVAX™ 2007 Process + M-M-R II™ VARIVAX™ 2007 Process 0.5 mL administered in the left arm and M-M-R II™ vaccine 0.5 mL administered in the right arm by subcutaneous injection on Day 1 and Day 91. | 305 |
| Total | 611 |
Baseline characteristics
| Characteristic | VARIVAX™ New Seed Process + M-M-R II™ | VARIVAX™ 2007 Process + M-M-R II™ | Total |
|---|---|---|---|
| Age, Continuous | 12.9 Months STANDARD_DEVIATION 1.9 | 12.8 Months STANDARD_DEVIATION 1.7 | 12.9 Months STANDARD_DEVIATION 1.8 |
| Sex: Female, Male Female | 140 Participants | 139 Participants | 279 Participants |
| Sex: Female, Male Male | 166 Participants | 166 Participants | 332 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 225 / 291 | 224 / 293 |
| serious Total, serious adverse events | 6 / 291 | 9 / 293 |
Outcome results
Primary
Geometric Mean Titer of VZV Antibodies
Antibody titers were measured with gpELISA.
Time frame: 6 weeks (43 days) after vaccination 1
Population: The analysis population is participants with seronegative antibody titer at baseline and postvaccination serology contributing to the per-protocol analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| VARIVAX™ New Seed Process + M-M-R II™ | Geometric Mean Titer of VZV Antibodies | 16.28 gpELISA units/mL |
| VARIVAX™ 2007 Process + M-M-R II™ | Geometric Mean Titer of VZV Antibodies | 17.2 gpELISA units/mL |
p-value: <0.00195% CI: [0.85, 1.06]t-test, 2 sided
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: [94.4, 98.9]Exact CI method/binomial proportion
Primary
Percentage of Participants With Varicella Zoster Virus (VZV) Antibody Levels >=5 Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Units/mL
Time frame: 6 weeks (43 days) after vaccination 1
Population: The analysis population is participants with a seronegative antibody titer at baseline and postvaccination serology contributing to the per-protocol analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Varicella Zoster Virus (VZV) Antibody Levels >=5 Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Units/mL | 97.2 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Varicella Zoster Virus (VZV) Antibody Levels >=5 Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Units/mL | 97.2 Percentage of participants |
p-value: <0.00195% CI: [-3.2, 3.2]Miettinen and Nurminen
Secondary
Percentage of Participants With Fever (>=102.2 °F Oral Equivalent)
Time frame: Up to 42 days after Vaccination 1 and Vaccination 2 (up to 133 days)
Population: The analysis population is All Subjects as Treated with temperature data at the time of assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Fever (>=102.2 °F Oral Equivalent) | Up to 42 days after Vaccination 1: n=285, 287 | 9.5 Percentage of participants |
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Fever (>=102.2 °F Oral Equivalent) | Up to 42 days after Vaccination 2: n=258, 267 | 8.1 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Fever (>=102.2 °F Oral Equivalent) | Up to 42 days after Vaccination 1: n=285, 287 | 10.5 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Fever (>=102.2 °F Oral Equivalent) | Up to 42 days after Vaccination 2: n=258, 267 | 8.6 Percentage of participants |
Secondary
Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 1
Time frame: Up to 5 days after Vaccination 1
Population: The analysis population is All Subjects as Treated with results after Vaccination 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 1 | Injection-site Erythema | 20.3 Percentage of participants |
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 1 | Injection-site Swelling | 10.0 Percentage of participants |
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 1 | Injection-site Pain/Tenderness | 29.9 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 1 | Injection-site Erythema | 19.8 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 1 | Injection-site Swelling | 10.6 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 1 | Injection-site Pain/Tenderness | 28.0 Percentage of participants |
Secondary
Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 2
Time frame: Up to 5 days after Vaccination 2
Population: The analysis population is All Subjects as Treated with results after vaccination 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VARIVAX™ New Seed Process + 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 | 20.6 Percentage of participants |
| VARIVAX™ New Seed Process + 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 | 16.2 Percentage of participants |
| VARIVAX™ New Seed Process + 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/Tenderness | 22.4 Percentage of participants |
| VARIVAX™ 2007 Process + 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 | 22.5 Percentage of participants |
| VARIVAX™ 2007 Process + 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 | 12.0 Percentage of participants |
| VARIVAX™ 2007 Process + 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/Tenderness | 24.3 Percentage of participants |
Secondary
Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 1
Time frame: Up to 42 days after Vaccination 1
Population: The analysis population is All Subjects as Treated with results after Vaccination 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 1 | Rubella-like Rash | 0.0 Percentage of participants |
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 1 | Mumps-like Symptoms | 0.0 Percentage of participants |
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 1 | Varicella-like Rash | 0.0 Percentage of participants |
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 1 | Injection-site Rash | 0.3 Percentage of participants |
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 1 | Measles-like Rash | 0.3 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 1 | Injection-site Rash | 1.4 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 1 | Measles-like Rash | 2.4 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 1 | Rubella-like Rash | 0.0 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 1 | Varicella-like Rash | 0.3 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 1 | Mumps-like Symptoms | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 2
Time frame: Up to 42 days after Vaccination 2
Population: The analysis population is All Subjects as Treated with results after vaccination 2
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 2 | Rubella-like Rash | 0.0 Percentage of participants |
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 2 | Mumps-like Symptoms | 0.0 Percentage of participants |
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 2 | Varicella-like Rash | 0.4 Percentage of participants |
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 2 | Injection-site Rash | 0.7 Percentage of participants |
| VARIVAX™ New Seed Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 2 | Measles-like Rash | 0.0 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 2 | Injection-site Rash | 0.0 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 2 | Measles-like Rash | 0.0 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 2 | Rubella-like Rash | 0.0 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 2 | Varicella-like Rash | 0.0 Percentage of participants |
| VARIVAX™ 2007 Process + M-M-R II™ | Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like Rash, Mumps-like Symptoms, and Injection-site Rash After Vaccination 2 | Mumps-like Symptoms | 0.0 Percentage of participants |