Measles, Mumps, Rubella, Varicella
Conditions
Keywords
Prevention of: measles, mumps, rubella and varicella
Brief summary
Primary objective: To describe the safety profile of a second dose of ProQuad® manufactured with recombinant human albumin (rHA) when administered to children in their second year of life. Secondary objectives: To describe the safety profile of a first dose of ProQuad® manufactured with rHA when administered to children in their second year of life.
Interventions
BIOLOGICALProQuad®
ProQuad® manufactured with recombinant human albumin (rHA) is an investigational combined attenuated live virus vaccine for vaccination against measles, mumps, rubella and varicella viruses.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to 22 Months
Healthy volunteers
Yes
Inclusion criteria
* Healthy subject of either gender, * Age from 12 to 22 months, * Negative clinical history of infection with measles, mumps, rubella, varicella or zoster, * Informed consent form signed by the parent(s) or by legal representative * Parent(s) or legal representative able to attend all schedule visits with the subject and to understand and comply with the study procedures
Exclusion criteria
* Recent (≤ 3 days) history of febrile illness * Prior receipt of measles, mumps, rubella and/or varicella vaccination, either alone or in any combination * Recent (≤ 30 days) exposure to measles, mumps, rubella, varicella or zoster * Prior known sensitivity/allergy to any component of the vaccine * Severe chronic disease, * Blood dyscrasias, leukaemia, lymphomas of any type, or other malignant neoplasms affecting the haematopoietic and lymphatic system * Any severe thrombocytopenia or any other coagulation disorder that would contraindicate intramuscular injection * Humoral or cellular immunodeficiency, * Current immunosuppressive therapy * Family history of congenital or hereditary immunodeficiency * Hereditary problems of fructose intolerance * Known personal history of encephalopathy, seizure disorder or progressive, evolving or unstable neurological condition, * Known active tuberculosis * Recent (≤ 2 days) tuberculin test or scheduled tuberculin test through Visit 3 * Receipt of immunoglobulins or blood-derived products in the past 150 days * Receipt of an inactivated vaccine in the past 14 days * Receipt of a live vaccine in the past 28 days * Any medical condition which, in the opinion of the investigator, might interfere with the evaluation of study objectives * Participation in another clinical study in the past 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing a Vaccine-related SAE After ProQuad® Dose 2 | Up to Day 84 (up to 42 days after ProQuad® Dose 2) | Vaccine-related SAEs were defined as any untoward consequence that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, is a congenital anomaly/birth defect, or is any other medically important event. |
| Percentage of Participants Experiencing a Systemic AE After ProQuad® Dose 2 | Up to Day 70 (up to 28 days after ProQuad® Dose 2) | Systemic AEs were monitored for up to 28 days after the second ProQuad® injection. |
| Percentage of Participants Experiencing a Vaccine-related Systemic AE After ProQuad® Dose 2 | Up to Day 70 (up to 28 days after ProQuad® Dose 2) | Vaccine-related systemic AEs were monitored for up to 28 days after the second ProQuad® injection. |
| Percentage of Participants Experiencing a Non-injection-site Rash of Interest AE After ProQuad® Dose 2 | Up to Day 70 (up to 28 days after ProQuad® Dose 2) | Non-injection-site rashes of interest, including measles-like, rubella-like, varicella-like, and zoster-like rashes, were monitored for up to 28 days after the second ProQuad® injection. |
| Percentage of Participants Experiencing a Serious AE (SAE) After ProQuad® Dose 2 | Up to Day 84 (up to 42 days after ProQuad® Dose 2) | Serious AEs ere defined as any untoward consequence that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, is a congenital anomaly/birth defect, or is any other medically important event. |
| Percentage of Participants Experiencing a Mumps-like Illness After ProQuad® Dose 2 | Up to Day 70 (up to 28 days after ProQuad® Dose 2) | The percentage of participants experiencing a mumps-like illness for up to 28 days after the second ProQuad® injection was determined. |
| Percentage of Participants Experiencing an Adverse Event (AE) After ProQuad® Dose 2 | Up to Day 70 (up to 28 days after ProQuad® Dose 2) | The percentage of participants experiencing an AE(s) for up to 28 days after the second ProQuad® injection was determined. |
| Percentage of Participants Experiencing a Vaccine-related AE After ProQuad® Dose 2 | Up to Day 70 (up to 28 days after ProQuad® Dose 2) | The percentage of participants experiencing a vaccine-related AEs for up to 28 days after the second ProQuad® injection was determined. |
| Percentage of Participants Experiencing a Solicited Injection-site AE After ProQuad® Dose 2 | Up to Day 46 (for 4 days following ProQuad® Dose 2) | The solicited injection-site AEs erythema, swelling, and pain were monitored for 4 days after administration of ProQuad® Dose 2. |
| Percentage of Participants Experiencing a Unsolicited Injection-site AE After ProQuad® Dose 2 | Up to Day 70 (up to 28 days after ProQuad® Dose 2) | The percentage of participants experiencing a unsolicited injection-site AE(s) were monitored for up to 28 days after the second ProQuad® injection. |
| Percentage of Participants Experiencing a Injection-site Rash of Interest AE After ProQuad® Dose 2 | Up to Day 70 (up to 28 days after ProQuad® Dose 2) | Injection-site rashes of interest, including measles-like, rubella-like, and vesicular, were monitored for up to 28 days after the second ProQuad® injection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing a Unsolicited Injection-site AE After ProQuad® Dose 1 | Up to Day 28 (28 days after ProQuad® Dose 1) | Unsolicited injection-site AEs were monitored for up to 28 days after the first ProQuad® injection. |
| Percentage of Participants With ≥ 1 Rectal Temperature Reading ≥ 38.0° C After ProQuad® Dose 1 | Up to Day 28 (28 days after ProQuad® Dose 1) | The percentage of participants with at least 1 rectal temperature reading ≥ 38.0° C was determined. |
| Percentage of Participants Experiencing a Systemic AE After ProQuad® Dose 1 | Up to Day 28 (28 days after ProQuad® Dose 1) | Systemic AEs were monitored for up to 28 days after the first ProQuad® injection. |
| Percentage of Participants Experiencing a Solicited Injection-site AE After ProQuad® Dose 1 | From Day 1 to Day 4 (for 4 days following ProQuad® Dose 1) | The solicited injection-site AEs erythema, swelling, and pain were monitored for 4 days after administration of ProQuad® Dose 1. |
Participant flow
Recruitment details
Healthy pediatric participants were enrolled at 84 study centers in 7 European countries.
Participants by arm
| Arm | Count |
|---|---|
| ProQuad® Healthy infants (12 to 22 months of age) received 2 doses of ProQuad® (Dose 1 on Day 1 and Dose 2 on Day 28 to 42) via subcutaneous injection into the deltoid muscle. | 3,388 |
| Total | 3,388 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Lost to Follow-up | 9 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Protocol Violation | 15 |
| Overall Study | Withdrawal by Subject | 26 |
Baseline characteristics
| Characteristic | ProQuad® |
|---|---|
| Age, Continuous | 14.6 Months STANDARD_DEVIATION 2.3 |
| Sex: Female, Male Female | 1650 Participants |
| Sex: Female, Male Male | 1738 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1,507 / 3,342 | 2,057 / 3,376 |
| serious Total, serious adverse events | 22 / 3,342 | 40 / 3,376 |
Outcome results
Primary
Percentage of Participants Experiencing a Injection-site Rash of Interest AE After ProQuad® Dose 2
Injection-site rashes of interest, including measles-like, rubella-like, and vesicular, were monitored for up to 28 days after the second ProQuad® injection.
Time frame: Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Population: All participants who received the second ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad® | Percentage of Participants Experiencing a Injection-site Rash of Interest AE After ProQuad® Dose 2 | 0.03 Percentage of Participants |
Primary
Percentage of Participants Experiencing a Mumps-like Illness After ProQuad® Dose 2
The percentage of participants experiencing a mumps-like illness for up to 28 days after the second ProQuad® injection was determined.
Time frame: Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Population: All participants who received the second ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad® | Percentage of Participants Experiencing a Mumps-like Illness After ProQuad® Dose 2 | 0.03 Percentage of Participants |
Primary
Percentage of Participants Experiencing an Adverse Event (AE) After ProQuad® Dose 2
The percentage of participants experiencing an AE(s) for up to 28 days after the second ProQuad® injection was determined.
Time frame: Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Population: All participants who received the second ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad® | Percentage of Participants Experiencing an Adverse Event (AE) After ProQuad® Dose 2 | 57.66 Percentage of Participants |
Primary
Percentage of Participants Experiencing a Non-injection-site Rash of Interest AE After ProQuad® Dose 2
Non-injection-site rashes of interest, including measles-like, rubella-like, varicella-like, and zoster-like rashes, were monitored for up to 28 days after the second ProQuad® injection.
Time frame: Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Population: All participants who received the second ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ProQuad® | Percentage of Participants Experiencing a Non-injection-site Rash of Interest AE After ProQuad® Dose 2 | Measles-like rash | 1.62 Percentage of Participants |
| ProQuad® | Percentage of Participants Experiencing a Non-injection-site Rash of Interest AE After ProQuad® Dose 2 | Rubella-like rash | 0.57 Percentage of Participants |
| ProQuad® | Percentage of Participants Experiencing a Non-injection-site Rash of Interest AE After ProQuad® Dose 2 | Varicella-like rash | 0.63 Percentage of Participants |
| ProQuad® | Percentage of Participants Experiencing a Non-injection-site Rash of Interest AE After ProQuad® Dose 2 | Zoster-like rash | 0.03 Percentage of Participants |
Primary
Percentage of Participants Experiencing a Serious AE (SAE) After ProQuad® Dose 2
Serious AEs ere defined as any untoward consequence that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, is a congenital anomaly/birth defect, or is any other medically important event.
Time frame: Up to Day 84 (up to 42 days after ProQuad® Dose 2)
Population: All participants who received the first ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad® | Percentage of Participants Experiencing a Serious AE (SAE) After ProQuad® Dose 2 | 0.66 Percentage of Participants |
Primary
Percentage of Participants Experiencing a Solicited Injection-site AE After ProQuad® Dose 2
The solicited injection-site AEs erythema, swelling, and pain were monitored for 4 days after administration of ProQuad® Dose 2.
Time frame: Up to Day 46 (for 4 days following ProQuad® Dose 2)
Population: All participants who received the second ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ProQuad® | Percentage of Participants Experiencing a Solicited Injection-site AE After ProQuad® Dose 2 | Injection-site erythema | 30.46 Percentage of Participants |
| ProQuad® | Percentage of Participants Experiencing a Solicited Injection-site AE After ProQuad® Dose 2 | Injection-site swelling | 13.23 Percentage of Participants |
| ProQuad® | Percentage of Participants Experiencing a Solicited Injection-site AE After ProQuad® Dose 2 | Injection-site pain | 11.49 Percentage of Participants |
Primary
Percentage of Participants Experiencing a Systemic AE After ProQuad® Dose 2
Systemic AEs were monitored for up to 28 days after the second ProQuad® injection.
Time frame: Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Population: All participants who received the second ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad® | Percentage of Participants Experiencing a Systemic AE After ProQuad® Dose 2 | 40.42 Percentage of Participants |
Primary
Percentage of Participants Experiencing a Unsolicited Injection-site AE After ProQuad® Dose 2
The percentage of participants experiencing a unsolicited injection-site AE(s) were monitored for up to 28 days after the second ProQuad® injection.
Time frame: Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Population: All participants who received the second ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad® | Percentage of Participants Experiencing a Unsolicited Injection-site AE After ProQuad® Dose 2 | 1.65 Percentage of Participants |
Primary
Percentage of Participants Experiencing a Vaccine-related AE After ProQuad® Dose 2
The percentage of participants experiencing a vaccine-related AEs for up to 28 days after the second ProQuad® injection was determined.
Time frame: Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Population: All participants who received the second ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad® | Percentage of Participants Experiencing a Vaccine-related AE After ProQuad® Dose 2 | 41.77 Percentage of Participants |
Primary
Percentage of Participants Experiencing a Vaccine-related SAE After ProQuad® Dose 2
Vaccine-related SAEs were defined as any untoward consequence that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, is a congenital anomaly/birth defect, or is any other medically important event.
Time frame: Up to Day 84 (up to 42 days after ProQuad® Dose 2)
Population: All participants who received the first ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad® | Percentage of Participants Experiencing a Vaccine-related SAE After ProQuad® Dose 2 | 0.21 Percentage of Participants |
Primary
Percentage of Participants Experiencing a Vaccine-related Systemic AE After ProQuad® Dose 2
Vaccine-related systemic AEs were monitored for up to 28 days after the second ProQuad® injection.
Time frame: Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Population: All participants who received the second ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad® | Percentage of Participants Experiencing a Vaccine-related Systemic AE After ProQuad® Dose 2 | 13.44 Percentage of Participants |
Secondary
Percentage of Participants Experiencing a Solicited Injection-site AE After ProQuad® Dose 1
The solicited injection-site AEs erythema, swelling, and pain were monitored for 4 days after administration of ProQuad® Dose 1.
Time frame: From Day 1 to Day 4 (for 4 days following ProQuad® Dose 1)
Population: All participants who received the first ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ProQuad® | Percentage of Participants Experiencing a Solicited Injection-site AE After ProQuad® Dose 1 | Injection-site erythema | 14.31 Percentage of Participants |
| ProQuad® | Percentage of Participants Experiencing a Solicited Injection-site AE After ProQuad® Dose 1 | Injection-site swelling | 5.57 Percentage of Participants |
| ProQuad® | Percentage of Participants Experiencing a Solicited Injection-site AE After ProQuad® Dose 1 | Injection-site pain | 10.31 Percentage of Participants |
Secondary
Percentage of Participants Experiencing a Systemic AE After ProQuad® Dose 1
Systemic AEs were monitored for up to 28 days after the first ProQuad® injection.
Time frame: Up to Day 28 (28 days after ProQuad® Dose 1)
Population: All participants who received the first ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad® | Percentage of Participants Experiencing a Systemic AE After ProQuad® Dose 1 | 64.10 Percentage of Participants |
Secondary
Percentage of Participants Experiencing a Unsolicited Injection-site AE After ProQuad® Dose 1
Unsolicited injection-site AEs were monitored for up to 28 days after the first ProQuad® injection.
Time frame: Up to Day 28 (28 days after ProQuad® Dose 1)
Population: All participants who received the first ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad® | Percentage of Participants Experiencing a Unsolicited Injection-site AE After ProQuad® Dose 1 | 7.43 Percentage of Participants |
Secondary
Percentage of Participants With ≥ 1 Rectal Temperature Reading ≥ 38.0° C After ProQuad® Dose 1
The percentage of participants with at least 1 rectal temperature reading ≥ 38.0° C was determined.
Time frame: Up to Day 28 (28 days after ProQuad® Dose 1)
Population: All participants who received the first ProQuad® dose and had safety follow-up data available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProQuad® | Percentage of Participants With ≥ 1 Rectal Temperature Reading ≥ 38.0° C After ProQuad® Dose 1 | 56.10 Percentage of Participants |