Measles, Mumps, Rubella, Varicella
Conditions
Brief summary
This study will compare three consistency lots of ProQuad to each other as well as to M-M-R II and Varivax, administered concomitantly at different injection sites, with respect to immunogenicity, safety, and tolerability.
Interventions
A Single 0.5 mL subcutaneous injection at Day 0
BIOLOGICALComparator: Varivax
A Single 0.5 mL subcutaneous injection at Day 0
BIOLOGICALComparator: M-M-R II
A Single 0.5 mL subcutaneous injection at Day 0
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Months to 23 Months
Healthy volunteers
Yes
Inclusion criteria
* In good health * Negative clinical history of measles, mumps, rubella, varicella, and zoster
Exclusion criteria
* Previous receipt of measles, mumps, rubella and/or varicella vaccine either alone or in combination * Any immune impairment or deficiency * Exposure to measles, mumps, rubella, varicella, or zoster in the 4 weeks prior to vaccination * Vaccination with an inactive vaccine with in the past 14 days * Vaccination with a live vaccine within the past 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Postvaccination Varicella Antibody Titer ≥ 5 Glycoprotein Enzyme-Linked Immunosorbent Assay (gpELISA) Units/mL | 6 weeks Postvaccination | Antibody Response to Varicella at 6 Weeks Postvaccination for Subjects Initially With Varicella Antibody Titer \< 1.25 gpELISA units/mL at Baseline |
| Number of Participants With Postvaccination Measles Enzyme-Linked Immunosorbent Assay (ELISA) Antibody Titer ≥ 120 mIU/mL | 6 weeks Postvaccination | Antibody Response to Measles at 6 Weeks Postvaccination for Subjects Initially Seronegative (a titer \< 120 mIU/mL) to Measles at Baseline |
| Number of Participants With Postvaccination Mumps ELISA Antibody Titer ≥ 10 Ab Units/mL | 6 weeks Postvaccination | Antibody Response to Mumps at 6 Weeks Postvaccination for Subjects Initially Seronegative (a titer \< 10 Ab units/mL) to Mumps at Baseline |
| Number of Participants With Postvaccination Rubella ELISA Antibody Titer ≥ 10 IU/mL | 6 weeks Postvaccination | Antibody Response to Rubella at 6 Weeks Postvaccination for Subjects Initially Seronegative (a titer \< 10 IU/mL) to Rubella at Baseline |
| Antibody Response to Varicella for Subjects Initially With Varicella Antibody Titer < 1.25 gpELISA Units/mL at Baseline - Geometric Mean Titer | 6 weeks Postvaccination | Postvaccination observed Geometric Mean Titer of antibody to Varicella |
| Antibody Response to Measles for Subjects Initially Seronegative (a Titer < 120 mIU/mL) to Measles at Baseline - Geometric Mean Titer | 6 weeks Postvaccination | Postvaccination observed Geometric Mean Titer of antibody to Measles. |
| Antibody Response to Mumps for Subjects Initially Seronegative (a Titer < 10 Ab Units/mL) to Mumps at Baseline - Geometric Mean Titer | 6 weeks Postvaccination | Postvaccination observed Geometric Mean Titer of antibody to Mumps. |
| Antibody Response to Rubella for Subjects Initially Seronegative (a Titer < 10 IU/mL) to Rubella at Baseline - Geometric Mean Titer | 6 weeks Postvaccination | Postvaccination observed Geometric Mean Titer of antibody to Rubella |
| Number of Participants With Serious Vaccine-related CAEs | 6 weeks Postvaccination | Subjects with a serious vaccine-related CAE (an AE which is assessed by an investigator/qualified physician as being related to study vaccine and results in death, persistent or significant disability/incapacity, prolongs an existing inpatient hospitalization, is life-threatening, a congenital anomaly/birth defect, a cancer, or an overdose). |
Participant flow
Recruitment details
35 clinical sites in the United States and 5 clinical sites in Canada Date of first participant visit: 12-Apr-2000 Date of last participant visit: 11-May-2001
Participants by arm
| Arm | Count |
|---|---|
| ProQuad™ Lot 1 ProQuad™ (measles, mumps, rubella, and varicella vaccine) Lot 1 administered on Day 0. ProQuad™ Lot 1 = ProQuad™ containing a varicella dose of 4.40 log10 PFU/0.5 mL. | 985 |
| ProQuad™ Lot 2 ProQuad™ (measles, mumps, rubella, and varicella vaccine) Lot 2 administered on Day 0. ProQuad™ Lot 2 = ProQuad™ containing a varicella dose of 4.61 log10 PFU/0.5 mL. | 968 |
| ProQuad™ Lot 3 ProQuad™ (measles, mumps, rubella, and varicella vaccine) Lot 1 administered on Day 0. ProQuad™ Lot 3 = ProQuad™ containing a varicella dose of 4.73 log10 PFU/0.5 mL. | 962 |
| M-M-R™ II + VARIVAX™ VARIVAX™ + M-M-R™ II administered concomitantly at separate injection sites on Day 0. | 1,012 |
| Total | 3,927 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Incomplete Safety Follow-up | 3 | 5 | 4 | 4 |
| Overall Study | Lost to Follow-up | 16 | 19 | 17 | 20 |
| Overall Study | Missed One or More Bleeds | 7 | 7 | 8 | 10 |
| Overall Study | Protocol Violation | 3 | 2 | 4 | 3 |
| Overall Study | Withdrawal by Subject | 6 | 11 | 11 | 10 |
Baseline characteristics
| Characteristic | ProQuad™ Lot 1 | Total | M-M-R™ II + VARIVAX™ | ProQuad™ Lot 3 | ProQuad™ Lot 2 |
|---|---|---|---|---|---|
| Age, Continuous | 12.7 Months STANDARD_DEVIATION 1.3 | 12.7 Months STANDARD_DEVIATION 1.4 | 12.8 Months STANDARD_DEVIATION 1.4 | 12.7 Months STANDARD_DEVIATION 1.3 | 12.8 Months STANDARD_DEVIATION 1.4 |
| Race/Ethnicity, Customized African American | 120 participants | 528 participants | 150 participants | 136 participants | 122 participants |
| Race/Ethnicity, Customized Asian/Pacific | 49 participants | 191 participants | 43 participants | 40 participants | 59 participants |
| Race/Ethnicity, Customized Caucasian | 615 participants | 2514 participants | 647 participants | 622 participants | 630 participants |
| Race/Ethnicity, Customized Hispanic | 150 participants | 498 participants | 119 participants | 116 participants | 113 participants |
| Race/Ethnicity, Customized Native American | 4 participants | 9 participants | 2 participants | 3 participants | 0 participants |
| Race/Ethnicity, Customized Other | 47 participants | 187 participants | 51 participants | 45 participants | 44 participants |
| Sex: Female, Male Female | 478 Participants | 1836 Participants | 468 Participants | 442 Participants | 448 Participants |
| Sex: Female, Male Male | 507 Participants | 2091 Participants | 544 Participants | 520 Participants | 520 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 793 / 969 | 758 / 950 | 769 / 941 | 785 / 993 |
| serious Total, serious adverse events | 6 / 969 | 8 / 950 | 11 / 941 | 11 / 993 |
Outcome results
Primary
Antibody Response to Measles for Subjects Initially Seronegative (a Titer < 120 mIU/mL) to Measles at Baseline - Geometric Mean Titer
Postvaccination observed Geometric Mean Titer of antibody to Measles.
Time frame: 6 weeks Postvaccination
Population: Per-protocol analysis set includes participants who had pre- and postvaccination blood samples within predefined day ranges, were seronegative to measles at baseline, and followed protocol procedures.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ProQuad™ Lot 1 | Antibody Response to Measles for Subjects Initially Seronegative (a Titer < 120 mIU/mL) to Measles at Baseline - Geometric Mean Titer | 3031.6 mIU/mL |
| ProQuad™ Lot 2 | Antibody Response to Measles for Subjects Initially Seronegative (a Titer < 120 mIU/mL) to Measles at Baseline - Geometric Mean Titer | 2939.3 mIU/mL |
| ProQuad™ Lot 3 | Antibody Response to Measles for Subjects Initially Seronegative (a Titer < 120 mIU/mL) to Measles at Baseline - Geometric Mean Titer | 2852.2 mIU/mL |
| M-M-R™ II + VARIVAX™ | Antibody Response to Measles for Subjects Initially Seronegative (a Titer < 120 mIU/mL) to Measles at Baseline - Geometric Mean Titer | 2095.6 mIU/mL |
Primary
Antibody Response to Mumps for Subjects Initially Seronegative (a Titer < 10 Ab Units/mL) to Mumps at Baseline - Geometric Mean Titer
Postvaccination observed Geometric Mean Titer of antibody to Mumps.
Time frame: 6 weeks Postvaccination
Population: Per-protocol analysis set includes participants who had pre- and postvaccination blood samples within predefined day ranges, were seronegative to mumps at baseline, and followed protocol procedures.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ProQuad™ Lot 1 | Antibody Response to Mumps for Subjects Initially Seronegative (a Titer < 10 Ab Units/mL) to Mumps at Baseline - Geometric Mean Titer | 100.5 ELISA AB units |
| ProQuad™ Lot 2 | Antibody Response to Mumps for Subjects Initially Seronegative (a Titer < 10 Ab Units/mL) to Mumps at Baseline - Geometric Mean Titer | 102.3 ELISA AB units |
| ProQuad™ Lot 3 | Antibody Response to Mumps for Subjects Initially Seronegative (a Titer < 10 Ab Units/mL) to Mumps at Baseline - Geometric Mean Titer | 85.6 ELISA AB units |
| M-M-R™ II + VARIVAX™ | Antibody Response to Mumps for Subjects Initially Seronegative (a Titer < 10 Ab Units/mL) to Mumps at Baseline - Geometric Mean Titer | 89.7 ELISA AB units |
Primary
Antibody Response to Rubella for Subjects Initially Seronegative (a Titer < 10 IU/mL) to Rubella at Baseline - Geometric Mean Titer
Postvaccination observed Geometric Mean Titer of antibody to Rubella
Time frame: 6 weeks Postvaccination
Population: Per-protocol analysis set includes participants who had pre- and postvaccination blood samples within predefined day ranges, were seronegative to rubella at baseline, and followed protocol procedures.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ProQuad™ Lot 1 | Antibody Response to Rubella for Subjects Initially Seronegative (a Titer < 10 IU/mL) to Rubella at Baseline - Geometric Mean Titer | 113.5 ELISA AB units |
| ProQuad™ Lot 2 | Antibody Response to Rubella for Subjects Initially Seronegative (a Titer < 10 IU/mL) to Rubella at Baseline - Geometric Mean Titer | 114.8 ELISA AB units |
| ProQuad™ Lot 3 | Antibody Response to Rubella for Subjects Initially Seronegative (a Titer < 10 IU/mL) to Rubella at Baseline - Geometric Mean Titer | 114.2 ELISA AB units |
| M-M-R™ II + VARIVAX™ | Antibody Response to Rubella for Subjects Initially Seronegative (a Titer < 10 IU/mL) to Rubella at Baseline - Geometric Mean Titer | 132.6 ELISA AB units |
Primary
Antibody Response to Varicella for Subjects Initially With Varicella Antibody Titer < 1.25 gpELISA Units/mL at Baseline - Geometric Mean Titer
Postvaccination observed Geometric Mean Titer of antibody to Varicella
Time frame: 6 weeks Postvaccination
Population: Per-protocol analysis set includes participants who had pre- and postvaccination blood samples within predefined day ranges, Varicella Antibody Titer \< 1.25 gpELISA units/mL at baseline, and followed protocol procedures.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ProQuad™ Lot 1 | Antibody Response to Varicella for Subjects Initially With Varicella Antibody Titer < 1.25 gpELISA Units/mL at Baseline - Geometric Mean Titer | 16.0 gpELISA |
| ProQuad™ Lot 2 | Antibody Response to Varicella for Subjects Initially With Varicella Antibody Titer < 1.25 gpELISA Units/mL at Baseline - Geometric Mean Titer | 18.4 gpELISA |
| ProQuad™ Lot 3 | Antibody Response to Varicella for Subjects Initially With Varicella Antibody Titer < 1.25 gpELISA Units/mL at Baseline - Geometric Mean Titer | 19.7 gpELISA |
| M-M-R™ II + VARIVAX™ | Antibody Response to Varicella for Subjects Initially With Varicella Antibody Titer < 1.25 gpELISA Units/mL at Baseline - Geometric Mean Titer | 17.6 gpELISA |
Primary
Number of Participants With Postvaccination Measles Enzyme-Linked Immunosorbent Assay (ELISA) Antibody Titer ≥ 120 mIU/mL
Antibody Response to Measles at 6 Weeks Postvaccination for Subjects Initially Seronegative (a titer \< 120 mIU/mL) to Measles at Baseline
Time frame: 6 weeks Postvaccination
Population: Per-protocol analysis set includes participants who had pre- and postvaccination blood samples within predefined day ranges, were seronegative to measles at baseline, and followed protocol procedures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad™ Lot 1 | Number of Participants With Postvaccination Measles Enzyme-Linked Immunosorbent Assay (ELISA) Antibody Titer ≥ 120 mIU/mL | 790 Participants |
| ProQuad™ Lot 2 | Number of Participants With Postvaccination Measles Enzyme-Linked Immunosorbent Assay (ELISA) Antibody Titer ≥ 120 mIU/mL | 753 Participants |
| ProQuad™ Lot 3 | Number of Participants With Postvaccination Measles Enzyme-Linked Immunosorbent Assay (ELISA) Antibody Titer ≥ 120 mIU/mL | 753 Participants |
| M-M-R™ II + VARIVAX™ | Number of Participants With Postvaccination Measles Enzyme-Linked Immunosorbent Assay (ELISA) Antibody Titer ≥ 120 mIU/mL | 800 Participants |
Primary
Number of Participants With Postvaccination Mumps ELISA Antibody Titer ≥ 10 Ab Units/mL
Antibody Response to Mumps at 6 Weeks Postvaccination for Subjects Initially Seronegative (a titer \< 10 Ab units/mL) to Mumps at Baseline
Time frame: 6 weeks Postvaccination
Population: Per-protocol analysis set includes participants who had pre- and postvaccination blood samples within predefined day ranges, were seronegative to mumps at baseline, and followed protocol procedures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad™ Lot 1 | Number of Participants With Postvaccination Mumps ELISA Antibody Titer ≥ 10 Ab Units/mL | 825 Participants |
| ProQuad™ Lot 2 | Number of Participants With Postvaccination Mumps ELISA Antibody Titer ≥ 10 Ab Units/mL | 796 Participants |
| ProQuad™ Lot 3 | Number of Participants With Postvaccination Mumps ELISA Antibody Titer ≥ 10 Ab Units/mL | 788 Participants |
| M-M-R™ II + VARIVAX™ | Number of Participants With Postvaccination Mumps ELISA Antibody Titer ≥ 10 Ab Units/mL | 854 Participants |
Primary
Number of Participants With Postvaccination Rubella ELISA Antibody Titer ≥ 10 IU/mL
Antibody Response to Rubella at 6 Weeks Postvaccination for Subjects Initially Seronegative (a titer \< 10 IU/mL) to Rubella at Baseline
Time frame: 6 weeks Postvaccination
Population: Per-protocol analysis set includes participants who had pre- and postvaccination blood samples within predefined day ranges, were seronegative to rubella at baseline, and followed protocol procedures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad™ Lot 1 | Number of Participants With Postvaccination Rubella ELISA Antibody Titer ≥ 10 IU/mL | 852 Participants |
| ProQuad™ Lot 2 | Number of Participants With Postvaccination Rubella ELISA Antibody Titer ≥ 10 IU/mL | 821 Participants |
| ProQuad™ Lot 3 | Number of Participants With Postvaccination Rubella ELISA Antibody Titer ≥ 10 IU/mL | 828 Participants |
| M-M-R™ II + VARIVAX™ | Number of Participants With Postvaccination Rubella ELISA Antibody Titer ≥ 10 IU/mL | 859 Participants |
Primary
Number of Participants With Postvaccination Varicella Antibody Titer ≥ 5 Glycoprotein Enzyme-Linked Immunosorbent Assay (gpELISA) Units/mL
Antibody Response to Varicella at 6 Weeks Postvaccination for Subjects Initially With Varicella Antibody Titer \< 1.25 gpELISA units/mL at Baseline
Time frame: 6 weeks Postvaccination
Population: Per-protocol analysis set includes participants who had pre- and postvaccination blood samples within predefined day ranges, Varicella Antibody Titer \<1.25 gpELISA units/mL at baseline, and followed protocol procedures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad™ Lot 1 | Number of Participants With Postvaccination Varicella Antibody Titer ≥ 5 Glycoprotein Enzyme-Linked Immunosorbent Assay (gpELISA) Units/mL | 726 Participants |
| ProQuad™ Lot 2 | Number of Participants With Postvaccination Varicella Antibody Titer ≥ 5 Glycoprotein Enzyme-Linked Immunosorbent Assay (gpELISA) Units/mL | 718 Participants |
| ProQuad™ Lot 3 | Number of Participants With Postvaccination Varicella Antibody Titer ≥ 5 Glycoprotein Enzyme-Linked Immunosorbent Assay (gpELISA) Units/mL | 736 Participants |
| M-M-R™ II + VARIVAX™ | Number of Participants With Postvaccination Varicella Antibody Titer ≥ 5 Glycoprotein Enzyme-Linked Immunosorbent Assay (gpELISA) Units/mL | 772 Participants |
Primary
Number of Participants With Serious Vaccine-related CAEs
Subjects with a serious vaccine-related CAE (an AE which is assessed by an investigator/qualified physician as being related to study vaccine and results in death, persistent or significant disability/incapacity, prolongs an existing inpatient hospitalization, is life-threatening, a congenital anomaly/birth defect, a cancer, or an overdose).
Time frame: 6 weeks Postvaccination
Population: All subjects with follow-up for safety were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ProQuad™ Lot 1 | Number of Participants With Serious Vaccine-related CAEs | With Serious Vaccine-Related CAEs | 2 Participants |
| ProQuad™ Lot 1 | Number of Participants With Serious Vaccine-related CAEs | Without Serious Vaccine-Related CAEs | 967 Participants |
| ProQuad™ Lot 2 | Number of Participants With Serious Vaccine-related CAEs | Without Serious Vaccine-Related CAEs | 949 Participants |
| ProQuad™ Lot 2 | Number of Participants With Serious Vaccine-related CAEs | With Serious Vaccine-Related CAEs | 1 Participants |
| ProQuad™ Lot 3 | Number of Participants With Serious Vaccine-related CAEs | With Serious Vaccine-Related CAEs | 2 Participants |
| ProQuad™ Lot 3 | Number of Participants With Serious Vaccine-related CAEs | Without Serious Vaccine-Related CAEs | 939 Participants |
| M-M-R™ II + VARIVAX™ | Number of Participants With Serious Vaccine-related CAEs | With Serious Vaccine-Related CAEs | 1 Participants |
| M-M-R™ II + VARIVAX™ | Number of Participants With Serious Vaccine-related CAEs | Without Serious Vaccine-Related CAEs | 992 Participants |