Measles, Mumps, Rubella, Varicella
Conditions
Brief summary
This study will compare the safety, tolerability, and immunogenicity of measles, mumps, rubella, and varicella (MMRV) vaccine made with an alternative manufacturing process with those of the 2006 process
Interventions
BIOLOGICALMMRV (AMP)
Measles, mumps, rubella, and VZV vaccine made with an alternative manufacturing process. Participants will receive two 0.5 mL subcutaneous injections.
BIOLOGICALMMRV (2006 process)
Measles, mumps, rubella, and VZV vaccine made with the 2006 manufacturing process. Participants will receive two 0.5 mL subcutaneous injections.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Months to 23 Months
Healthy volunteers
Yes
Inclusion criteria
* Negative clinical history for measles, mumps, rubella, varicella, and zoster
Exclusion criteria
* Received any measles, mumps, rubella, or varicella vaccine, either alone or in any combination at any time prior to the study, or is anticipated to receive any of these vaccines outside of study protocol, either alone or in any combination, during the study * Received immune globulin, a blood transfusion or blood-derived products (does not include autologous blood/blood products) within 5 months (150 days) prior to any dose of the study vaccines or plans to receive these products while enrolled in this study * Exposed to measles, mumps, rubella, varicella, or zoster within 4 weeks prior to the study vaccination * Any congenital or acquired immune deficiency, neoplastic disease, or depressed immunity, including that resulting from steroid use or other immunosuppressive therapy * Received 1) systemic immunomodulatory steroids \[greater than the equivalent of 2 mg/kg total daily dose of prednisone\] within 3 months prior to entering the study, or 2) any dose of systemic immunomodulatory steroids within 7 days prior to entering study, or 3) is expected to require systemic immunomodulatory steroids through the course of the study * History of allergy or anaphylactoid reaction to gelatin, sorbitol, neomycin, egg proteins (eggs or egg products), chicken proteins, or any component of the study vaccines * Received salicylates (eg, aspirin or aspirin-containing products) within 14 days prior to study vaccination * Diagnosis of an active neurological disorder. Enrollment may be considered when the disease process has been stabilized * History of seizure disorder, including single febrile seizure * Diagnosis of active untreated tuberculosis * History of thrombocytopenia * Born to a human immunodeficiency virus (HIV) infected mother
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Fever (>=102.2°F [39.0°C] or Oral Equivalent) | Up to 5 days after vaccination 1 | — |
| Geometric Mean Titer (GMT) of Measles Virus Antibodies | Six weeks after vaccination 1 | Sera were tested for measles virus IgG antibody levels by ELISA |
| Percentage of Participants With Varicella Zoster Virus (VZV) Antibody Levels >=5 gpELISA Units/mL | Six weeks after vaccination 1 | Sera were tested for VZV Immunoglobulin (IgG) antibody levels by a glycoprotein enzyme-linked immunosorbent assay (gpELISA) |
| Percentage of Participants With Measles Virus Antibody Levels >=255 mIU/mL | Six weeks after vaccination 1 | Sera were tested for measles virus IgG antibody levels by an ELISA |
| Percentage of Participants With Mumps Virus Antibody Levels >=10 Units/mL | Six weeks after vaccination 1 | Sera were tested for mumps virus IgG antibody levels by an enzyme-linked immunosorbent assay (ELISA) |
| Percentage of Participants With Rubella Virus Antibody Levels >=10 International Units/mL (IU/mL) | Six weeks after vaccination 1 | Sera were tested for rubella virus IgG antibody levels by an ELISA |
| Geometric Mean Titer (GMT) of Mumps Virus Antibodies | Six weeks after vaccination 1 | Sera were tested for mumps virus IgG antibody levels by ELISA |
| Geometric Mean Titer (GMT) of Rubella Virus Antibodies | Six weeks after vaccination 1 | Sera were tested for rubella virus IgG antibody levels by ELISA |
| Geometric Mean Titer (GMT) of VZV Antibodies | Six weeks after vaccination 1 | Sera were tested for VZV IgG antibody levels by gpELISA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Zoster-like Rash | Up to 42 days after each vaccination | — |
| Percentage of Participants With Mumps-like Symptoms | Up to 42 days after each vaccination | — |
| Percentage of Participants With Measles-like Rash | Up to 42 days after each vaccination | — |
| Percentage of Participants With Rubella-like Rash | Up to 42 days after each vaccination | — |
| Percentage of Participants With Varicella-like Rash | Up to 42 days after each vaccination | — |
| Percentage of Participants With an Injection-site Adverse Event | Up to 5 days after each vaccination | An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Injection-site AEs reported were solicited with a Vaccine Report Card. |
| Percentage of Participants With Fever (>=102.2°F [39.0°C] or Oral Equivalent) | Up to 42 days after each vaccination | — |
Participant flow
Pre-assignment details
One participant was inadvertently randomized twice, for a total of 1413 randomizations. The Participant Flow reported below includes this participant only once.
Participants by arm
| Arm | Count |
|---|---|
| MMRV (AMP) Participants were to received two 0.5 mL subcutaneous injections of Mumps, Measles, Rubella, Varicella (MMRV) vaccine made with an alternative manufacturing process (AMP) | 706 |
| MMRV (2006 Process) Participants were to receive two 0.5 mL subcutaneous injections of MMRV made with the 2006 manufacturing process | 706 |
| Total | 1,412 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomization to Visit 1 (Vaccination 1) | Not vaccinated | 8 | 4 |
| Visit 1 (Vaccination 1) to Visit 2 | Lost to Follow-up | 20 | 22 |
| Visit 1 (Vaccination 1) to Visit 2 | Withdrawal by Subject | 12 | 18 |
| Visit 2 to Visit 3 (Vaccination 2) | Adverse Event | 3 | 3 |
| Visit 2 to Visit 3 (Vaccination 2) | Lost to Follow-up | 9 | 10 |
| Visit 2 to Visit 3 (Vaccination 2) | Protocol Violation | 2 | 2 |
| Visit 2 to Visit 3 (Vaccination 2) | Withdrawal by Subject | 17 | 13 |
| Visit 3 (Vaccination 2) to Visit 4 | Adverse Event | 1 | 0 |
| Visit 3 (Vaccination 2) to Visit 4 | Lost to Follow-up | 16 | 14 |
| Visit 3 (Vaccination 2) to Visit 4 | Withdrawal by Subject | 3 | 2 |
| Visit 4 to Extended Study Follow-up | Adverse Event | 0 | 1 |
| Visit 4 to Extended Study Follow-up | Lost to Follow-up | 20 | 20 |
| Visit 4 to Extended Study Follow-up | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | MMRV (AMP) | MMRV (2006 Process) | Total |
|---|---|---|---|
| Age, Continuous | 13.4 Months STANDARD_DEVIATION 2.2 | 13.6 Months STANDARD_DEVIATION 2.5 | 13.5 Months STANDARD_DEVIATION 2.3 |
| Sex: Female, Male Female | 344 Participants | 324 Participants | 668 Participants |
| Sex: Female, Male Male | 362 Participants | 382 Participants | 744 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 574 / 682 | 572 / 683 |
| serious Total, serious adverse events | 21 / 682 | 18 / 683 |
Outcome results
Primary
Geometric Mean Titer (GMT) of Measles Virus Antibodies
Sera were tested for measles virus IgG antibody levels by ELISA
Time frame: Six weeks after vaccination 1
Population: The per protocol population included participants who received \>=1 dose of study vaccine, were seronegative at baseline and had postvaccination measles virus serology results
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MMRV (AMP) | Geometric Mean Titer (GMT) of Measles Virus Antibodies | 3426.5 mIU/mL |
| MMRV (2006 Process) | Geometric Mean Titer (GMT) of Measles Virus Antibodies | 3719.5 mIU/mL |
p-value: <0.00195% CI: [0.8, 1]t-test, 2 sided
Primary
Geometric Mean Titer (GMT) of Mumps Virus Antibodies
Sera were tested for mumps virus IgG antibody levels by ELISA
Time frame: Six weeks after vaccination 1
Population: The per protocol population included participants who received \>=1 dose of study vaccine, were seronegative at baseline and had postvaccination mumps virus serology results
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MMRV (AMP) | Geometric Mean Titer (GMT) of Mumps Virus Antibodies | 112.1 Mumps Ab units/mL |
| MMRV (2006 Process) | Geometric Mean Titer (GMT) of Mumps Virus Antibodies | 114.0 Mumps Ab units/mL |
p-value: <0.00195% CI: [0.9, 1.1]t-test, 2 sided
Primary
Geometric Mean Titer (GMT) of Rubella Virus Antibodies
Sera were tested for rubella virus IgG antibody levels by ELISA
Time frame: Six weeks after vaccination 1
Population: The per protocol population included participants who received \>=1 dose of study vaccine, were seronegative at baseline and had postvaccination rubella virus serology results
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MMRV (AMP) | Geometric Mean Titer (GMT) of Rubella Virus Antibodies | 81.8 IU/mL |
| MMRV (2006 Process) | Geometric Mean Titer (GMT) of Rubella Virus Antibodies | 80.7 IU/mL |
p-value: <0.00195% CI: [0.9, 1.1]t-test, 2 sided
Primary
Geometric Mean Titer (GMT) of VZV Antibodies
Sera were tested for VZV IgG antibody levels by gpELISA
Time frame: Six weeks after vaccination 1
Population: The per protocol population included participants who received \>=1 dose of study vaccine, were seronegative at baseline and had postvaccination VZV serology results
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MMRV (AMP) | Geometric Mean Titer (GMT) of VZV Antibodies | 17.3 ELISA units/mL |
| MMRV (2006 Process) | Geometric Mean Titer (GMT) of VZV Antibodies | 14.4 ELISA units/mL |
p-value: <0.00195% CI: [1.1, 1.3]t-test, 2 sided
Primary
Percentage of Participants With Fever (>=102.2°F [39.0°C] or Oral Equivalent)
Time frame: Up to 5 days after vaccination 1
Population: The population analyzed included participants who received \>=1 study vaccination and had follow-up safety data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MMRV (AMP) | Percentage of Participants With Fever (>=102.2°F [39.0°C] or Oral Equivalent) | 0.9 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Fever (>=102.2°F [39.0°C] or Oral Equivalent) | 0.8 Percentage of participants |
p-value: <0.00195% CI: [-1, 1.3]Miettinen and Nurminen
Primary
Percentage of Participants With Measles Virus Antibody Levels >=255 mIU/mL
Sera were tested for measles virus IgG antibody levels by an ELISA
Time frame: Six weeks after vaccination 1
Population: The per protocol population included participants who received \>=1 dose of study vaccine, were seronegative at baseline and had postvaccination measles virus serology results
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MMRV (AMP) | Percentage of Participants With Measles Virus Antibody Levels >=255 mIU/mL | 96.7 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Measles Virus Antibody Levels >=255 mIU/mL | 98.9 Percentage of participants |
p-value: 0.00395% CI: [-4, -0.6]Miettinen and Nurminen
Comparison: Acceptability of the antibody response rate was based on a lower bound of the 95% CI being \>90%p-value: <0.00195% CI: [94.9, 97.9]One-sample binomial
Primary
Percentage of Participants With Mumps Virus Antibody Levels >=10 Units/mL
Sera were tested for mumps virus IgG antibody levels by an enzyme-linked immunosorbent assay (ELISA)
Time frame: Six weeks after vaccination 1
Population: The per protocol population included participants who received \>=1 dose of study vaccine, were seronegative at baseline and had postvaccination mumps virus serology results
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MMRV (AMP) | Percentage of Participants With Mumps Virus Antibody Levels >=10 Units/mL | 98.2 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Mumps Virus Antibody Levels >=10 Units/mL | 97.2 Percentage of participants |
p-value: <0.00195% CI: [-0.7, 2.8]Miettinen and Nurminen
Comparison: Acceptability of the antibody response rate was based on a lower bound of the 95% CI being \>90%p-value: <0.00195% CI: [96.8, 99.1]One-sample binomial
Primary
Percentage of Participants With Rubella Virus Antibody Levels >=10 International Units/mL (IU/mL)
Sera were tested for rubella virus IgG antibody levels by an ELISA
Time frame: Six weeks after vaccination 1
Population: The per protocol population included participants who received \>=1 dose of study vaccine, were seronegative at baseline and had postvaccination rubella serology results
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MMRV (AMP) | Percentage of Participants With Rubella Virus Antibody Levels >=10 International Units/mL (IU/mL) | 98.8 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Rubella Virus Antibody Levels >=10 International Units/mL (IU/mL) | 99.3 Percentage of participants |
p-value: <0.00195% CI: [-1.8, 0.7]Miettinen and Nurminen
Comparison: Acceptability of the antibody response rate was based on a lower bound of the 95% CI being \>90%p-value: <0.00195% CI: [97.6, 99.5]One-sample binomial
Primary
Percentage of Participants With Varicella Zoster Virus (VZV) Antibody Levels >=5 gpELISA Units/mL
Sera were tested for VZV Immunoglobulin (IgG) antibody levels by a glycoprotein enzyme-linked immunosorbent assay (gpELISA)
Time frame: Six weeks after vaccination 1
Population: The per protocol population included participants who received \>=1 dose of study vaccine, were seronegative at baseline and had postvaccination VZV serology results
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MMRV (AMP) | Percentage of Participants With Varicella Zoster Virus (VZV) Antibody Levels >=5 gpELISA Units/mL | 97.3 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Varicella Zoster Virus (VZV) Antibody Levels >=5 gpELISA Units/mL | 93.0 Percentage of participants |
p-value: <0.00195% CI: [1.8, 6.8]Miettinen and Nurminen
Comparison: Acceptability of the antibody response rate was based on a lower bound of the 95% CI being \>76%p-value: <0.00195% CI: [95.6, 98.4]One-sample binomial
Secondary
Percentage of Participants With an Injection-site Adverse Event
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Injection-site AEs reported were solicited with a Vaccine Report Card.
Time frame: Up to 5 days after each vaccination
Population: The population analyzed included participants who received \>=1 study vaccination and had follow-up safety data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MMRV (AMP) | Percentage of Participants With an Injection-site Adverse Event | Vaccination 1; n=682, n=682 | 36.4 Percentage of participants |
| MMRV (AMP) | Percentage of Participants With an Injection-site Adverse Event | Vaccination 2; n=634, n=632 | 35.5 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With an Injection-site Adverse Event | Vaccination 1; n=682, n=682 | 29.8 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With an Injection-site Adverse Event | Vaccination 2; n=634, n=632 | 29.6 Percentage of participants |
Secondary
Percentage of Participants With Fever (>=102.2°F [39.0°C] or Oral Equivalent)
Time frame: Up to 42 days after each vaccination
Population: The population analyzed included participants who received \>=1 study vaccination and had follow-up safety data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MMRV (AMP) | Percentage of Participants With Fever (>=102.2°F [39.0°C] or Oral Equivalent) | Vaccination 1; n=650, n=649 | 10.0 Percentage of participants |
| MMRV (AMP) | Percentage of Participants With Fever (>=102.2°F [39.0°C] or Oral Equivalent) | Vaccination 2; n=592, n=597 | 5.7 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Fever (>=102.2°F [39.0°C] or Oral Equivalent) | Vaccination 1; n=650, n=649 | 10.6 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Fever (>=102.2°F [39.0°C] or Oral Equivalent) | Vaccination 2; n=592, n=597 | 8.4 Percentage of participants |
Secondary
Percentage of Participants With Measles-like Rash
Time frame: Up to 42 days after each vaccination
Population: The population analyzed included participants who received \>=1 study vaccination and had follow-up safety data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MMRV (AMP) | Percentage of Participants With Measles-like Rash | Vaccination 1; n=682, n=682 | 0.1 Percentage of participants |
| MMRV (AMP) | Percentage of Participants With Measles-like Rash | Vaccination 2; n=634, n=632 | 0.2 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Measles-like Rash | Vaccination 1; n=682, n=682 | 0.3 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Measles-like Rash | Vaccination 2; n=634, n=632 | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Mumps-like Symptoms
Time frame: Up to 42 days after each vaccination
Population: The population analyzed included participants who received \>=1 study vaccination and had follow-up safety data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MMRV (AMP) | Percentage of Participants With Mumps-like Symptoms | Vaccination 1; n=682, n=682 | 0.0 Percentage of participants |
| MMRV (AMP) | Percentage of Participants With Mumps-like Symptoms | Vaccination 2; n=634, n=632 | 0.0 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Mumps-like Symptoms | Vaccination 1; n=682, n=682 | 0.0 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Mumps-like Symptoms | Vaccination 2; n=634, n=632 | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Rubella-like Rash
Time frame: Up to 42 days after each vaccination
Population: The population analyzed included participants who received \>=1 study vaccination and had follow-up safety data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MMRV (AMP) | Percentage of Participants With Rubella-like Rash | Vaccination 1; n=682, n=682 | 0.0 Percentage of participants |
| MMRV (AMP) | Percentage of Participants With Rubella-like Rash | Vaccination 2; n=634, n=632 | 0.0 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Rubella-like Rash | Vaccination 1; n=682, n=682 | 0.0 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Rubella-like Rash | Vaccination 2; n=634, n=632 | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Varicella-like Rash
Time frame: Up to 42 days after each vaccination
Population: The population analyzed included participants who received \>=1 study vaccination and had follow-up safety data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MMRV (AMP) | Percentage of Participants With Varicella-like Rash | Vaccination 1; n=682, n=682 | 0.6 Percentage of participants |
| MMRV (AMP) | Percentage of Participants With Varicella-like Rash | Vaccination 2; n=634, n=632 | 0.0 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Varicella-like Rash | Vaccination 1; n=682, n=682 | 0.0 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Varicella-like Rash | Vaccination 2; n=634, n=632 | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Zoster-like Rash
Time frame: Up to 42 days after each vaccination
Population: The population analyzed included participants who received \>=1 study vaccination and had follow-up safety data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MMRV (AMP) | Percentage of Participants With Zoster-like Rash | Vaccination 1; n=682, n=682 | 0.0 Percentage of participants |
| MMRV (AMP) | Percentage of Participants With Zoster-like Rash | Vaccination 2; n=634, n=632 | 0.0 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Zoster-like Rash | Vaccination 1; n=682, n=682 | 0.0 Percentage of participants |
| MMRV (2006 Process) | Percentage of Participants With Zoster-like Rash | Vaccination 2; n=634, n=632 | 0.0 Percentage of participants |