Measles, Mumps, Rubella, Varicella
Conditions
Brief summary
The primary study objectives are: * To demonstrate that a 2-dose regimen of ProQuad® manufactured with recombinant Human Albumin (rHA) administered at a 3-month interval to healthy children of 11 months of age at the time of Dose 1 is as immunogenic as in healthy children of 12 months of age at the time of Dose 1. * To demonstrate that a 2-dose regimen of ProQuad® rHA administered at a 3-month interval to healthy children of 9 months of age at the time of Dose 1 is as immunogenic as in healthy children of 12 months of age at the time of Dose 1. * To demonstrate that a 2-dose regimen of ProQuad® rHA administered at a 3-month interval to healthy children of 11 months of age and 9 months of age at the time of Dose 1 is well-tolerated compared to children of 12 months of age at the time of Dose 1. The first primary hypothesis was that a 2-dose regimen of ProQuad® rHA, administered at a 3-month interval to children of 11 months of age, would be non-inferior in terms of antibody response rates to measles, mumps, rubella, and varicella at Day 42 following Dose 2, to the same regimen in children of 12 months of age at the time of Dose 1. If the first primary hypothesis was demonstrated, the second primary hypothesis was that a 2-dose regimen of ProQuad® rHA, administered at a 3-month interval to children of 9 months of age, would be non-inferior in terms of antibody response rates to measles, mumps, rubella, and varicella at Day 42 following Dose 2, to the same regimen in children of 12 months of age at the time of Dose 1. The secondary study objectives are: * To describe the antibody titres to measles, mumps, rubella and varicella at Day 42 following Dose 1 and Dose 2 of ProQuad® rHA administered to healthy children from 9 months of age. * To evaluate the safety profile of Dose 1 and Dose 2 of ProQuad® rHA administered to healthy children from 9 months of age.
Interventions
BIOLOGICALProQuad® manufactured with recombinant Human Albumin (rHA)
A 2-dose regimen of ProQuad® (0.5 mL per dose) given via subcutaneous injection into the deltoid muscle at a 3-month interval. Each dose contains measles virus Enders' Edmonston strain (live attenuated), mumps virus Jeryl Lynn™ (Level B) strain (live attenuated), rubella virus Wistar RA 27 or 3 strain (live attenuated), and varicella virus Oka or Merck strain (live attenuated).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
9 Months to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Healthy subject of either gender of 9 months of age 2. Negative clinical history of measles, mumps, rubella, varicella or zoster 3. Informed consent form signed by both parents or legal representative 4. Parent(s) or legal representative able to attend all the scheduled visits with the subject and to understand and comply with the study procedures 5. Both parent or legal representative are over 18 years of age 6. Subject is affiliated to a health social security system
Exclusion criteria
1. Febrile illness in the previous 3 days 2. Prior vaccination with a measles, mumps, rubella and/or varicella vaccine either alone or in any combination 3. Exposure to measles, mumps, rubella, varicella and/or zoster in the previous 30 days 4. Tuberculin test done in the previous 2 days 5. Severe chronic disease 6. Known active tuberculosis 7. Known personal history of encephalopathy, seizure disorder or progressive, evolving or unstable neurological condition 8. Hereditary problems of fructose intolerance 9. Prior known sensitivity or allergy to any component of the vaccine 10. Known blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems 11. Humoral or cellular immunodeficiency, 12. Immunosuppressive therapy \[including systemic corticosteroids (a), given daily or on alternate days at high doses (\>=2 mg/kg/day prednisone equivalent or \>=20 mg/day if the subject's weight was \>10 kg) during at least 14 days in the previous 30 days\] 13. Family history of congenital or hereditary immunodeficiency 14. Receipt of immunoglobulins or blood-derived products in the previous 150 days or scheduled to be administered through Visit 5 15. Receipt of an inactivated vaccine in the previous 14 days 16. Receipt of a live non-study vaccine in the previous 28 days 17. Any medical condition which, in the opinion of the investigator, might have interfered with the evaluation of the study objectives 18. Current participation or scheduled participation in any other clinical study through Visit 5
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Rectal (or Rectal Equivalent) Temperature ≥ 39.4°C | Up to Day 28 (up to 28 days after ProQuad® Dose 1) | The percentage of participants with a rectal (or rectal equivalent) temperature ≥ 39.4°C after ProQuad® Dose 1 was determined. |
| Percentage of Participants in Arm 2 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Day 132 (6 weeks after ProQuad® Dose 2) | Immunogenicity response rates were compared in participants with baseline seronegativity from Arm 2 (received ProQuad® Dose 1 at 11 months) and Arm 3 (received ProQuad® Dose 1 at 12 months). Measles, mumps and rubella antibody levels were determined using enzyme-linked immunosorbent assay (ELISA) and varicella antibody levels were determined with glycoprotein-based ELISA (gpELISA). Response and baseline seronegativity criteria were as follows: measles antibody titre ≥255 mIU/mL in participants with baseline titre \<255 mIU/mL; mumps antibody titre ≥10 ELISA Ab units/mL in participants with baseline titre \<10 ELISA Ab units mL; rubella antibody titre ≥10 IU/mL in participants with baseline titre \<10 IU/mL; varicella antibody titre ≥5 gpELISA units/mL in participants with baseline titre \<1.25 gpELISA units/mL. |
| Percentage of Participants in Arm 1 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Day 132 (6 weeks after ProQuad® Dose 2) | Immunogenicity response rates were compared in participants with baseline seronegativity from Arm 1 (received ProQuad® Dose 1 at 9 months) and Arm 3 (received ProQuad® Dose 1 at 12 months). Measles, mumps and rubella antibody levels were determined using ELISA and varicella antibody levels were determined with gpELISA. Response and baseline seronegativity criteria were as follows: measles antibody titre ≥255 mIU/mL in participants with baseline titre \<255 mIU/mL; mumps antibody titre ≥10 ELISA Ab units/mL in participants with baseline titre \<10 ELISA Ab units mL; rubella antibody titre ≥10 IU/mL in participants with baseline titre \<10 IU/mL; varicella antibody titre ≥5 gpELISA units/mL in participants with baseline titre \<1.25 gpELISA units/mL. |
| Percentage of Participants With Solicited Injection-site Adverse Reactions | Day 1 to Day 4 (up to 4 days after ProQuad® Dose 1) | The solicited injection-site AEs erythema, swelling, and pain were monitored for 4 days after administration of ProQuad® Dose 1. |
| Percentage of Participants Experiencing Unsolicited Injection-site Adverse Reactions | Up to Day 28 (up to 28 days after ProQuad® Dose 1) | The percentage of participants with unsolicited injection-site reactions after ProQuad® Dose 1 was determined. |
| Percentage of Participants Experiencing a Systemic Adverse Event After ProQuad® Dose 1 | Up to Day 28 (up to 28 days after ProQuad® Dose 1) | The percentage of participants with systemic adverse events after ProQuad® Dose 1 was determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1 | Day 42 (6 weeks after ProQuad® Dose 1) | Antibody titres (GMT) to measles, mumps, rubella, and varicella were determined after the first ProQuad® dose in participants with seronegative baseline values. Baseline seronegativity criteria were as follows: measles antibody titre \<255 mIU/mL; mumps antibody titre \<10 ELISA Ab units mL; rubella antibody titre \<10 IU/mL; and varicella antibody titre \<1.25 gpELISA units/mL. |
| GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2 | Day 132 (6 weeks after ProQuad® Dose 2) | Antibody titres (GMT) to measles, mumps, rubella, and varicella were determined after the second ProQuad® dose in participants with seronegative baseline values. Baseline seronegativity criteria were as follows: measles antibody titre \<255 mIU/mL; mumps antibody titre \<10 ELISA Ab units mL; rubella antibody titre \<10 IU/mL; and varicella antibody titre \<1.25 gpELISA units/mL. |
| Percentage of Participants With Varicella Antibody Titre ≥ 1.25 gpELISA Units/mL | Day 132 (6 weeks after ProQuad® Dose 2) | The percentage of participants with varicella antibody titre ≥ 1.25 gpELISA units/mL 6 weeks after each ProQuad® dose was determined. |
| Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1 | Day 42 (6 weeks after ProQuad® Dose 1) | The percentage of baseline seronegative participants meeting measles, mumps, rubella, and varicella antibody response criteria after the first ProQuad® dose was determined. Measles, mumps and rubella antibody levels were determined using ELISA and varicella antibody levels were determined with gpELISA. Response and baseline seronegativity criteria were as follows: measles antibody titre ≥255 mIU/mL in participants with baseline titre \<255 mIU/mL; mumps antibody titre ≥10 ELISA Ab units/mL in participants with baseline titre \<10 ELISA Ab units mL; rubella antibody titre ≥10 IU/mL in participants with baseline titre \<10 IU/mL; varicella antibody titre ≥5 gpELISA units/mL in participants with baseline titre \<1.25 gpELISA units/mL. |
| Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Up to Day 28 (up to 4 weeks after ProQuad® Dose 1) | The percentage of participants with rashes of interest after ProQuad® Dose 1 was determined. Rashes of interest consisted of measles-like rash, rubella-like rash, varicella-like rash, zoster-like rash, and mumps-like rash. |
| Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Day 132 (6 weeks after ProQuad® Dose 2) | The percentage of participants with rashes of interest after receiving ProQuad® Dose 2 was determined. Rashes of interest consisted of measles-like rash, rubella-like rash, varicella-like rash, zoster-like rash, and mumps-like rash. |
Participant flow
Recruitment details
Pediatric participants from 9 to 12 months of age at the start of the study were recruited at 48 study centers in Finland, France, and Germany.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: ProQuad® at 9 and 12 Months Pediatric participants received ProQuad® Dose 1 at 9 months of age and ProQuad® Dose 2 90 days later at 12 months of age. | 541 |
| Arm 2: ProQuad® at 11 and 14 Months Pediatric participants received ProQuad® Dose 1 at 11 months of age and ProQuad® Dose 2 90 days later at 14 months of age. | 540 |
| Arm 3: ProQuad® at 12 and 15 Months Pediatric participants received ProQuad® Dose 1 at 12 months of age and ProQuad® Dose 2 90 days later at 15 months of age. | 539 |
| Total | 1,620 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 4 | 4 |
| Overall Study | Physician Decision | 3 | 8 | 20 |
| Overall Study | Reason not provided | 3 | 11 | 10 |
| Overall Study | Withdrawal by Subject | 6 | 43 | 43 |
Baseline characteristics
| Characteristic | Arm 1: ProQuad® at 9 and 12 Months | Arm 2: ProQuad® at 11 and 14 Months | Arm 3: ProQuad® at 12 and 15 Months | Total |
|---|---|---|---|---|
| Age, Continuous | 9.47 Months STANDARD_DEVIATION 0.29 | 9.48 Months STANDARD_DEVIATION 0.3 | 9.47 Months STANDARD_DEVIATION 9.43 | 9.48 Months STANDARD_DEVIATION 0.3 |
| Sex: Female, Male Female | 282 Participants | 281 Participants | 258 Participants | 821 Participants |
| Sex: Female, Male Male | 259 Participants | 259 Participants | 281 Participants | 799 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 468 / 541 | 430 / 540 | 401 / 539 |
| serious Total, serious adverse events | 21 / 541 | 15 / 540 | 17 / 539 |
Outcome results
Primary
Percentage of Participants Experiencing a Systemic Adverse Event After ProQuad® Dose 1
The percentage of participants with systemic adverse events after ProQuad® Dose 1 was determined.
Time frame: Up to Day 28 (up to 28 days after ProQuad® Dose 1)
Population: All participants who received ProQuad® Dose 1 and have safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants Experiencing a Systemic Adverse Event After ProQuad® Dose 1 | 72.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants Experiencing a Systemic Adverse Event After ProQuad® Dose 1 | 71.9 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants Experiencing a Systemic Adverse Event After ProQuad® Dose 1 | 71.9 Percentage of participants |
Primary
Percentage of Participants Experiencing Unsolicited Injection-site Adverse Reactions
The percentage of participants with unsolicited injection-site reactions after ProQuad® Dose 1 was determined.
Time frame: Up to Day 28 (up to 28 days after ProQuad® Dose 1)
Population: All participants who received ProQuad® Dose 1 and have safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants Experiencing Unsolicited Injection-site Adverse Reactions | 24.8 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants Experiencing Unsolicited Injection-site Adverse Reactions | 23.3 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants Experiencing Unsolicited Injection-site Adverse Reactions | 19.1 Percentage of participants |
Primary
Percentage of Participants in Arm 1 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2
Immunogenicity response rates were compared in participants with baseline seronegativity from Arm 1 (received ProQuad® Dose 1 at 9 months) and Arm 3 (received ProQuad® Dose 1 at 12 months). Measles, mumps and rubella antibody levels were determined using ELISA and varicella antibody levels were determined with gpELISA. Response and baseline seronegativity criteria were as follows: measles antibody titre ≥255 mIU/mL in participants with baseline titre \<255 mIU/mL; mumps antibody titre ≥10 ELISA Ab units/mL in participants with baseline titre \<10 ELISA Ab units mL; rubella antibody titre ≥10 IU/mL in participants with baseline titre \<10 IU/mL; varicella antibody titre ≥5 gpELISA units/mL in participants with baseline titre \<1.25 gpELISA units/mL.
Time frame: Day 132 (6 weeks after ProQuad® Dose 2)
Population: All baseline seronegative participants with immunogenicity data are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants in Arm 1 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Measles | 94.9 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants in Arm 1 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Mumps | 99.2 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants in Arm 1 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Rubella | 99.4 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants in Arm 1 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Varicella | 100.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants in Arm 1 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Varicella | 100.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants in Arm 1 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Measles | 98.8 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants in Arm 1 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Rubella | 99.5 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants in Arm 1 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Mumps | 99.5 Percentage of participants |
Comparison: Measles difference95% CI: [-6.44, -1.87]
Comparison: Mumps difference95% CI: [-1.71, 1.01]
Comparison: Rubella difference95% CI: [-1.34, 1.09]
Comparison: Varicella difference95% CI: [-1.83, 1.1]
Primary
Percentage of Participants in Arm 2 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2
Immunogenicity response rates were compared in participants with baseline seronegativity from Arm 2 (received ProQuad® Dose 1 at 11 months) and Arm 3 (received ProQuad® Dose 1 at 12 months). Measles, mumps and rubella antibody levels were determined using enzyme-linked immunosorbent assay (ELISA) and varicella antibody levels were determined with glycoprotein-based ELISA (gpELISA). Response and baseline seronegativity criteria were as follows: measles antibody titre ≥255 mIU/mL in participants with baseline titre \<255 mIU/mL; mumps antibody titre ≥10 ELISA Ab units/mL in participants with baseline titre \<10 ELISA Ab units mL; rubella antibody titre ≥10 IU/mL in participants with baseline titre \<10 IU/mL; varicella antibody titre ≥5 gpELISA units/mL in participants with baseline titre \<1.25 gpELISA units/mL.
Time frame: Day 132 (6 weeks after ProQuad® Dose 2)
Population: All baseline seronegative participants with immunogenicity data are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants in Arm 2 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Measles | 98.0 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants in Arm 2 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Mumps | 99.5 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants in Arm 2 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Rubella | 99.3 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants in Arm 2 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Varicella | 100.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants in Arm 2 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Varicella | 100.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants in Arm 2 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Measles | 98.8 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants in Arm 2 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Rubella | 99.5 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants in Arm 2 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2 | Mumps | 99.5 Percentage of participants |
Comparison: Measles difference95% CI: [-2.82, 0.87]
Comparison: Mumps difference95% CI: [-1.2, 1.32]
Comparison: Rubella difference95% CI: [-1.55, 1.03]
Comparison: Varicella difference95% CI: [-1.28, 1.1]
Primary
Percentage of Participants With Rectal (or Rectal Equivalent) Temperature ≥ 39.4°C
The percentage of participants with a rectal (or rectal equivalent) temperature ≥ 39.4°C after ProQuad® Dose 1 was determined.
Time frame: Up to Day 28 (up to 28 days after ProQuad® Dose 1)
Population: All participants who received ProQuad® Dose 1 and have safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Rectal (or Rectal Equivalent) Temperature ≥ 39.4°C | 8.8 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Rectal (or Rectal Equivalent) Temperature ≥ 39.4°C | 10.3 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Rectal (or Rectal Equivalent) Temperature ≥ 39.4°C | 14.8 Percentage of participants |
Primary
Percentage of Participants With Solicited Injection-site Adverse Reactions
The solicited injection-site AEs erythema, swelling, and pain were monitored for 4 days after administration of ProQuad® Dose 1.
Time frame: Day 1 to Day 4 (up to 4 days after ProQuad® Dose 1)
Population: All participants who received ProQuad® Dose 1 and have safety follow-up data available are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Solicited Injection-site Adverse Reactions | Injection-site pain | 11.4 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Solicited Injection-site Adverse Reactions | Injection-site erythema | 14.4 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Solicited Injection-site Adverse Reactions | Injection-site swelling | 2.3 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Solicited Injection-site Adverse Reactions | Injection-site pain | 10.4 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Solicited Injection-site Adverse Reactions | Injection-site erythema | 15.4 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Solicited Injection-site Adverse Reactions | Injection-site swelling | 4.6 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Solicited Injection-site Adverse Reactions | Injection-site erythema | 17.2 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Solicited Injection-site Adverse Reactions | Injection-site swelling | 2.4 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Solicited Injection-site Adverse Reactions | Injection-site pain | 13.7 Percentage of participants |
Secondary
Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1
Antibody titres (GMT) to measles, mumps, rubella, and varicella were determined after the first ProQuad® dose in participants with seronegative baseline values. Baseline seronegativity criteria were as follows: measles antibody titre \<255 mIU/mL; mumps antibody titre \<10 ELISA Ab units mL; rubella antibody titre \<10 IU/mL; and varicella antibody titre \<1.25 gpELISA units/mL.
Time frame: Day 42 (6 weeks after ProQuad® Dose 1)
Population: All participants with seronegative baselines who received ProQuad® Dose 1 and have immunogenicity data available are included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Arm 2: ProQuad® at 11 and 14 Months | Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1 | Measles (mIU/mL) | 942 GMT |
| Arm 2: ProQuad® at 11 and 14 Months | Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1 | Mumps (ELISA Ab units/mL) | 73 GMT |
| Arm 2: ProQuad® at 11 and 14 Months | Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1 | Rubella (IU/mL) | 64 GMT |
| Arm 2: ProQuad® at 11 and 14 Months | Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1 | Varicella (gpELISA units/mL) | 15 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1 | Varicella (gpELISA units/mL) | 15 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1 | Measles (mIU/mL) | 1977 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1 | Rubella (IU/mL) | 77 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1 | Mumps (ELISA Ab units/mL) | 91 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1 | Varicella (gpELISA units/mL) | 15 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1 | Mumps (ELISA Ab units/mL) | 86 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1 | Rubella (IU/mL) | 81 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1 | Measles (mIU/mL) | 2500 GMT |
Secondary
GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2
Antibody titres (GMT) to measles, mumps, rubella, and varicella were determined after the second ProQuad® dose in participants with seronegative baseline values. Baseline seronegativity criteria were as follows: measles antibody titre \<255 mIU/mL; mumps antibody titre \<10 ELISA Ab units mL; rubella antibody titre \<10 IU/mL; and varicella antibody titre \<1.25 gpELISA units/mL.
Time frame: Day 132 (6 weeks after ProQuad® Dose 2)
Population: All participants with seronegative baselines who received ProQuad® Dose 2 and have immunogenicity data available are included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Arm 2: ProQuad® at 11 and 14 Months | GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2 | Varicella {gpELISA units/mL) | 431 GMT |
| Arm 2: ProQuad® at 11 and 14 Months | GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2 | Measles (mIU/mL) | 1817 GMT |
| Arm 2: ProQuad® at 11 and 14 Months | GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2 | Rubella (IU/mL) | 106 GMT |
| Arm 2: ProQuad® at 11 and 14 Months | GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2 | Mumps (ELISA Ab units/mL) | 157 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2 | Rubella (IU/mL) | 116 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2 | Varicella {gpELISA units/mL) | 460 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2 | Mumps (ELISA Ab units/mL) | 163 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2 | Measles (mIU/mL) | 2320 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2 | Varicella {gpELISA units/mL) | 515 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2 | Mumps (ELISA Ab units/mL) | 172 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2 | Rubella (IU/mL) | 118 GMT |
| Arm 3: ProQuad® at 12 and 15 Months | GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2 | Measles (mIU/mL) | 2703 GMT |
Secondary
Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1
The percentage of baseline seronegative participants meeting measles, mumps, rubella, and varicella antibody response criteria after the first ProQuad® dose was determined. Measles, mumps and rubella antibody levels were determined using ELISA and varicella antibody levels were determined with gpELISA. Response and baseline seronegativity criteria were as follows: measles antibody titre ≥255 mIU/mL in participants with baseline titre \<255 mIU/mL; mumps antibody titre ≥10 ELISA Ab units/mL in participants with baseline titre \<10 ELISA Ab units mL; rubella antibody titre ≥10 IU/mL in participants with baseline titre \<10 IU/mL; varicella antibody titre ≥5 gpELISA units/mL in participants with baseline titre \<1.25 gpELISA units/mL.
Time frame: Day 42 (6 weeks after ProQuad® Dose 1)
Population: All baseline seronegative participants with immunogenicity data are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1 | Measles | 72.6 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1 | Mumps | 96.6 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1 | Rubella | 97.7 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1 | Varicella | 95.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1 | Varicella | 97.8 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1 | Measles | 87.9 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1 | Rubella | 98.9 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1 | Mumps | 98.7 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1 | Varicella | 97.5 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1 | Mumps | 98.3 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1 | Rubella | 98.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1 | Measles | 90.2 Percentage of participants |
Secondary
Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1
The percentage of participants with rashes of interest after ProQuad® Dose 1 was determined. Rashes of interest consisted of measles-like rash, rubella-like rash, varicella-like rash, zoster-like rash, and mumps-like rash.
Time frame: Up to Day 28 (up to 4 weeks after ProQuad® Dose 1)
Population: All participants who received ProQuad® Dose 1 and have safety follow-up data available are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Rubella-like rash | 1.3 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Measles-like rash | 4.0 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Varicella-like rash | 5.3 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Mumps-like illness | 0.0 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Zoster-like rash | 0.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Mumps-like illness | 0.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Measles-like rash | 5.8 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Rubella-like rash | 1.9 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Varicella-like rash | 4.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Zoster-like rash | 0.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Varicella-like rash | 6.4 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Measles-like rash | 6.9 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Mumps-like illness | 0.4 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Rubella-like rash | 1.5 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1 | Zoster-like rash | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2
The percentage of participants with rashes of interest after receiving ProQuad® Dose 2 was determined. Rashes of interest consisted of measles-like rash, rubella-like rash, varicella-like rash, zoster-like rash, and mumps-like rash.
Time frame: Day 132 (6 weeks after ProQuad® Dose 2)
Population: All participants who received ProQuad® Dose 2 and have safety follow-up data available are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Mumps-like illness | 0.0 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Measles-like rash | 2.1 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Rubella-like rash | 1.5 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Varicella-like rash | 2.1 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Zoster-like rash | 0.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Varicella-like rash | 3.8 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Zoster-like rash | 0.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Measles-like rash | 2.7 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Mumps-like illness | 0.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Rubella-like rash | 1.9 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Zoster-like rash | 0.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Rubella-like rash | 0.9 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Varicella-like rash | 2.6 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Mumps-like illness | 0.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2 | Measles-like rash | 2.8 Percentage of participants |
Secondary
Percentage of Participants With Varicella Antibody Titre ≥ 1.25 gpELISA Units/mL
The percentage of participants with varicella antibody titre ≥ 1.25 gpELISA units/mL 6 weeks after each ProQuad® dose was determined.
Time frame: Day 132 (6 weeks after ProQuad® Dose 2)
Population: All participants who received ProQuad® and have serology results are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Varicella Antibody Titre ≥ 1.25 gpELISA Units/mL | ProQuad® Dose 1 | 99.8 Percentage of participants |
| Arm 2: ProQuad® at 11 and 14 Months | Percentage of Participants With Varicella Antibody Titre ≥ 1.25 gpELISA Units/mL | ProQuad® Dose 2 | 100.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Varicella Antibody Titre ≥ 1.25 gpELISA Units/mL | ProQuad® Dose 1 | 100.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Varicella Antibody Titre ≥ 1.25 gpELISA Units/mL | ProQuad® Dose 2 | 100.0 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Varicella Antibody Titre ≥ 1.25 gpELISA Units/mL | ProQuad® Dose 1 | 99.8 Percentage of participants |
| Arm 3: ProQuad® at 12 and 15 Months | Percentage of Participants With Varicella Antibody Titre ≥ 1.25 gpELISA Units/mL | ProQuad® Dose 2 | 100.0 Percentage of participants |