Meningococcal Infections
Conditions
Keywords
vaccine, toddlers, healthy, meningitis, meningococcal, measles, mumps, rubella, varicella, Prevention of Meningococcal disease types ACWY
Brief summary
Safety immune response of Novartis MenACWY-CRM conjugate vaccine when given to healthy toddlers
Interventions
BIOLOGICALMenACWY-CRM + MMRV
One injection of MenACWY-CRM vaccine at 7-9 months of age; the second injection of MenACWY-CRM vaccine concomitantly administered with MMRV (Measles, Mumps, Rubella and Varicella) vaccine at 12 months of age.
BIOLOGICALMMRV
one injection of MMRV (Measles, Mumps, Rubella and Varicella) vaccine at 12 months of age
BIOLOGICALMenACWY-CRM
Two injections of MenACWY-CRM at 7-9 months and 12 months of age; one injection of MMRV (Measles, Mumps, Rubella and Varicella) at 13.5 months of age
Sponsors
Novartis Vaccines
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Months to 1 Years
Healthy volunteers
Yes
Inclusion criteria
* who are healthy 7 to 9 months old or 12 months old (inclusive plus 14 days) and for whom, after the nature of the study has been explained, the parent or legal guardian has provided written informed consent; * who have received complete primary vaccination with recommended licensed vaccines; * who are available for all visits and telephone calls scheduled for the study;
Exclusion criteria
* whose parent or legal guardian is unwilling or unable to give written informed assent consent * who had a previous or suspected disease caused by N. meningitidis; * who had previous or suspected infection with measles, mumps, rubella, varicella, and/or herpes zoster; * who had household contact with and/or intimate exposure to an individual with culture-proven N. meningitidis infection within 60 days prior to enrollment; * who had household contact with and/or intimate exposure to an individual with measles, mumps, rubella and/or varicella infection within 60 days prior to enrollment; * who have previously been immunized with a meningococcal vaccine or vaccine containing meningococcal antigen(s) * who have previously received any measles, mumps, rubella or varicella vaccine either alone or in any combination; * who have received any investigational agents or vaccines within 90 days prior to enrollment or who expect to receive an investigational agent or vaccine prior to the completion of the study; * who have any serious acute, chronic or progressive disease such as, cancer, diabetes, heart failure, malnutrition, epilepsy, HIV/AIDS, Guillain Barre Syndrome * who have a history of anaphylaxis, serious vaccine reactions or allergy to any part of the vaccine, * who have a known or suspected impairment/alteration of immune function, either congenital or acquired * who have Down's syndrome or other known cytogenic disorders; bleeding diathesis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentages of Subjects With a Seroresponse to Measles, Mumps, Rubella and Varicella Following Concomitant Administration of MMRV Vaccine With MenACWY-CRM Vaccine | 6 weeks post vaccination | Percentages of subjects with seroresponses to measles, mumps, rubella and varicella after one dose of MMRV vaccine (at 12 months) when given concomitantly with MenACWY-CRM vaccine compared to when MMRV vaccine was given alone, are reported. Seroresponse was defined as the percentage of initially seronegative subjects who show seroconversion to measles (≥255 mIU/mL), mumps (≥10 ELISA Ab units), rubella (≥10 IU/mL) and the percentage of initially seronegative subjects who show seroprotection (≥5 gp ELISA units/mL) for varicella. Immunogenicity to measles, mumps, rubella and varicella at 6 weeks after vaccination with one dose of MMRV given concomitantly with MenACWY-CRM was considered non-inferior to immunogenicity of MMRV administered alone if the lower limit of two-sided 95% CI of the difference in the percentage of subjects with seroconversion for measles, mumps, and rubella, and seroprotection for varicella was greater than -5% (measles, mumps and rubella) and -10% (varicella). |
| Percentages of Subjects With Serum Bactericidal Titers ≥1:8 Following Concomitant Administration of MenACWY-CRM Vaccine With MMRV Vaccine. | 6 weeks post second dose | Percentages of subjects with hSBA ≥1:8, against N.meningitidis serogroups A, C, W-135, and Y following two doses of MenACWY-CRM vaccine (at 7-9 months and 12 months) when concomitantly administered with MMRV vaccine (12 months) compared to when MenACWY-CRM vaccine was given alone, are reported. The serum bactericidal antibodies directed against N.meningitidis serogroups A, C, W-135, and Y, were measured by human complement Serum Bactericidal Assay (hSBA). The immune response of MenACWY-CRM given concomitantly with MMRV was considered non-inferior to the immunogenicity of MenACWY-CRM administered alone if the lower limit of the two-sided 95% CI around the difference of the percentage of subjects with hSBA ≥1:8 at 6 weeks after the second dose of MenACWY-CRM given to 12-month old toddlers {P MMRV+MenACWY minus P MenACWY} was greater than -10% for each serogroup. |
| Percentages of Subjects With hSBA ≥1:8 Following Two Doses of MenACWY-CRM Vaccine | 6 weeks post vaccine dose 2 | The antibody response following two doses of MenACWY-CRM vaccine (at 7-9 months and 12 months) was considered adequate if the lower limit of the two-sided 95% CI for the percentage of subjects with hSBA ≥1:8, at 6 weeks following the second dose of MenACWY-CRM, was greater than 85% for serogroups C, W-135, or Y and greater than 65% for serogroup A. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentages of Subjects Showing Seroconversion Response to Varicella Following Concomitant Administration of MMRV With MenACWY-CRM Vaccine. | 6 weeks post vaccination | The percentages of subjects showing seroconversion response to varicella after concomitant administration of MMRV vaccine (at 12 months) with MenACWY-CRM vaccine compared to when MMRV vaccine is given alone, is reported . Seroconversion for varicella is defined as percentage of subjects who show pre-vaccination antibody titer \<1.25 gp ELISA units/mL to a post-vaccination antibody titer ≥1.25 gp ELISA units/mL. |
| Percentages of Subjects With hSBA ≥1:4 and hSBA ≥1:8 Following One Dose of MenACWY-CRM Vaccine | 1 month post vaccine dose 1 | The percentages of subjects with hSBA ≥1:4 and hSBA ≥1:8 after one dose of MenACWY-CRM vaccine (at 7-9 months), are reported |
| Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine | 6 weeks post vaccine dose 2 | The percentages of subjects with hSBA ≥1:4 directed against N. meningitidis serogroups A, C, W-135, and Y following two doses of MenACWY-CRM vaccine (at 7-9 and 12 months of age) when given concomitantly with MMRV vaccine (at 12 months) compared to when MenACWY-CRM vaccine was given alone, are reported. |
| Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | upto 7 days after any vaccination | Safety and tolerability of MenACWY-CRM and MMRV vaccines when given concomitantly compared to when either MenACWY-CRM or MMRV vaccine was administered alone is reported in terms of the number of subjects with local and systemic adverse events after vaccination. Systemic reactions including axillary temperature reported during 28 days after vaccination at 12 months of age. These included the following systemic reactions: Measles-like rash, Rubella-like rash, Varicellalike rash, injection site rash, Mumps-like symptoms and axillary temperature. |
| Number of Subjects Reporting Unsolicited Adverse Events After Vaccination | Day 1- Day 180 (Through out the study) | The safety profile of MenACWY-CRM and MMRV vaccines when given concomitantly as compared to when MenACWY-CRM or MMRV was given alone is reported in terms of number of subjects reporting unsolicited adverse events (AEs), medically significant adverse events and serious adverse events (SAEs) after vaccination. |
| Geometric Mean Titers After One Dose of MenACWY-CRM Vaccine | 1 month post vaccine dose 1 | The immunogenicity of one dose of MenACWY-CRM vaccine given at 7 to 9 months of age was assessed in terms of GMTs directed against N.meningitidis serogroups A, C, W-135, and Y. |
| Geometric Mean Titers Against Serogroups A, C, W-135 and Y, Following Two Doses of MenACWY-CRM Vaccine | 6 weeks post vaccine dose 2 | The geometric mean titers (GMTs) directed against N.meningitidis serogroups A, C, W-135 and Y, following two doses of MenACWY-CRM vaccine (at 7-9 months and 12 months of age), when given concomitantly with MMRV vaccine (at 12 months) compared to when MenACWY-CRM vaccine was given alone, are reported. |
| Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | 6 weeks post vaccination | The GMTs directed against measles, mumps, rubella and varicella, following one dose of MMRV vaccine (at 12 months) when given concomitantly with MenACWY-CRM vaccine compared to when MMRV vaccine was given alone, are reported. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 90 centers in the USA
Pre-assignment details
All subjects enrolled were included in the trial.
Participants by arm
| Arm | Count |
|---|---|
| MenACWY-CRM+ MMRV Subjects in this group received 2 injections of MenACWY-CRM at 7-9 and 12 months; second injection administered concomitantly with MMRV | 504 |
| MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age | 616 |
| MenACWY-CRM Subjects in this group received 2 injections of the MenACWY-CRM vaccine at 7-9 and 12 months of age followed by 1 injection of MMRV at 13.5 months | 510 |
| Total | 1,630 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative Reason | 2 | 0 | 6 |
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Inappropriate enrollment | 4 | 5 | 3 |
| Overall Study | Lost to Follow-up | 24 | 21 | 23 |
| Overall Study | Protocol Violation | 26 | 4 | 26 |
| Overall Study | Withdrawal by Subject | 21 | 29 | 30 |
Baseline characteristics
| Characteristic | MenACWY-CRM+ MMRV | MMRV | MenACWY-CRM | Total |
|---|---|---|---|---|
| Age Continuous | 8.5 months STANDARD_DEVIATION 0.8 | 12.1 months STANDARD_DEVIATION 0.3 | 8.5 months STANDARD_DEVIATION 0.8 | 9.8 months STANDARD_DEVIATION 1.9 |
| Sex: Female, Male Female | 251 Participants | 304 Participants | 252 Participants | 807 Participants |
| Sex: Female, Male Male | 253 Participants | 312 Participants | 258 Participants | 823 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 | 433 / 500 | 482 / 597 | 442 / 500 |
| serious Total, serious adverse events | 18 / 500 | 9 / 597 | 19 / 500 |
Outcome results
Primary
Percentages of Subjects With a Seroresponse to Measles, Mumps, Rubella and Varicella Following Concomitant Administration of MMRV Vaccine With MenACWY-CRM Vaccine
Percentages of subjects with seroresponses to measles, mumps, rubella and varicella after one dose of MMRV vaccine (at 12 months) when given concomitantly with MenACWY-CRM vaccine compared to when MMRV vaccine was given alone, are reported. Seroresponse was defined as the percentage of initially seronegative subjects who show seroconversion to measles (≥255 mIU/mL), mumps (≥10 ELISA Ab units), rubella (≥10 IU/mL) and the percentage of initially seronegative subjects who show seroprotection (≥5 gp ELISA units/mL) for varicella. Immunogenicity to measles, mumps, rubella and varicella at 6 weeks after vaccination with one dose of MMRV given concomitantly with MenACWY-CRM was considered non-inferior to immunogenicity of MMRV administered alone if the lower limit of two-sided 95% CI of the difference in the percentage of subjects with seroconversion for measles, mumps, and rubella, and seroprotection for varicella was greater than -5% (measles, mumps and rubella) and -10% (varicella).
Time frame: 6 weeks post vaccination
Population: The analysis was performed on the MMRV per-protocol population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM+ MMRV | Percentages of Subjects With a Seroresponse to Measles, Mumps, Rubella and Varicella Following Concomitant Administration of MMRV Vaccine With MenACWY-CRM Vaccine | Measles (N=350,467) | 98 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With a Seroresponse to Measles, Mumps, Rubella and Varicella Following Concomitant Administration of MMRV Vaccine With MenACWY-CRM Vaccine | Mumps (N=365,499) | 98 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With a Seroresponse to Measles, Mumps, Rubella and Varicella Following Concomitant Administration of MMRV Vaccine With MenACWY-CRM Vaccine | Rubella | 95 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With a Seroresponse to Measles, Mumps, Rubella and Varicella Following Concomitant Administration of MMRV Vaccine With MenACWY-CRM Vaccine | Varicella (N=337,459) | 96 Percentages of subjects |
| MMRV | Percentages of Subjects With a Seroresponse to Measles, Mumps, Rubella and Varicella Following Concomitant Administration of MMRV Vaccine With MenACWY-CRM Vaccine | Varicella (N=337,459) | 98 Percentages of subjects |
| MMRV | Percentages of Subjects With a Seroresponse to Measles, Mumps, Rubella and Varicella Following Concomitant Administration of MMRV Vaccine With MenACWY-CRM Vaccine | Measles (N=350,467) | 99 Percentages of subjects |
| MMRV | Percentages of Subjects With a Seroresponse to Measles, Mumps, Rubella and Varicella Following Concomitant Administration of MMRV Vaccine With MenACWY-CRM Vaccine | Rubella | 97 Percentages of subjects |
| MMRV | Percentages of Subjects With a Seroresponse to Measles, Mumps, Rubella and Varicella Following Concomitant Administration of MMRV Vaccine With MenACWY-CRM Vaccine | Mumps (N=365,499) | 96 Percentages of subjects |
Comparison: Non-inferiority of immune response to measles following one dose of MMRV administered concomitantly with MenACWY-CRM as compared to MMRV given alone.95% CI: [-3.4, 0.5]
Comparison: Non-inferiority of immune response to mumps following one dose of MMRV administered concomitantly with MenACWY-CRM as compared to MMRV administered alone.95% CI: [-1, 3.7]
Comparison: Non-inferiority of immune response to rubella following one dose of MMRV administered concomitantly with MenACWY-CRM as compared to MMRV administered alone.95% CI: [-4.5, 0.8]
Comparison: Non-inferiority of immune response to varicella following one dose of MMRV administered concomitantly with MenACWY-CRM as compared to MMRV administered alone.95% CI: [-3.9, 1.2]
Primary
Percentages of Subjects With hSBA ≥1:8 Following Two Doses of MenACWY-CRM Vaccine
The antibody response following two doses of MenACWY-CRM vaccine (at 7-9 months and 12 months) was considered adequate if the lower limit of the two-sided 95% CI for the percentage of subjects with hSBA ≥1:8, at 6 weeks following the second dose of MenACWY-CRM, was greater than 85% for serogroups C, W-135, or Y and greater than 65% for serogroup A.
Time frame: 6 weeks post vaccine dose 2
Population: The analysis was performed on the MenACWY per-protocol population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:8 Following Two Doses of MenACWY-CRM Vaccine | Serogroup A | 88 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:8 Following Two Doses of MenACWY-CRM Vaccine | Serogroup C (N=195) | 100 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:8 Following Two Doses of MenACWY-CRM Vaccine | Serogroup W-135 (N=196) | 98 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:8 Following Two Doses of MenACWY-CRM Vaccine | Serogroup Y (N=198) | 96 Percentages of subjects |
Primary
Percentages of Subjects With Serum Bactericidal Titers ≥1:8 Following Concomitant Administration of MenACWY-CRM Vaccine With MMRV Vaccine.
Percentages of subjects with hSBA ≥1:8, against N.meningitidis serogroups A, C, W-135, and Y following two doses of MenACWY-CRM vaccine (at 7-9 months and 12 months) when concomitantly administered with MMRV vaccine (12 months) compared to when MenACWY-CRM vaccine was given alone, are reported. The serum bactericidal antibodies directed against N.meningitidis serogroups A, C, W-135, and Y, were measured by human complement Serum Bactericidal Assay (hSBA). The immune response of MenACWY-CRM given concomitantly with MMRV was considered non-inferior to the immunogenicity of MenACWY-CRM administered alone if the lower limit of the two-sided 95% CI around the difference of the percentage of subjects with hSBA ≥1:8 at 6 weeks after the second dose of MenACWY-CRM given to 12-month old toddlers {P MMRV+MenACWY minus P MenACWY} was greater than -10% for each serogroup.
Time frame: 6 weeks post second dose
Population: The analysis was performed on the MenACWY per-protocol population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM+ MMRV | Percentages of Subjects With Serum Bactericidal Titers ≥1:8 Following Concomitant Administration of MenACWY-CRM Vaccine With MMRV Vaccine. | Serogroup A | 88 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With Serum Bactericidal Titers ≥1:8 Following Concomitant Administration of MenACWY-CRM Vaccine With MMRV Vaccine. | Seroroup C (N=204,195) | 100 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With Serum Bactericidal Titers ≥1:8 Following Concomitant Administration of MenACWY-CRM Vaccine With MMRV Vaccine. | Sergroup W-135 (N=204,196) | 100 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With Serum Bactericidal Titers ≥1:8 Following Concomitant Administration of MenACWY-CRM Vaccine With MMRV Vaccine. | Serogroup Y (N=200,198) | 98 Percentages of subjects |
| MMRV | Percentages of Subjects With Serum Bactericidal Titers ≥1:8 Following Concomitant Administration of MenACWY-CRM Vaccine With MMRV Vaccine. | Serogroup Y (N=200,198) | 96 Percentages of subjects |
| MMRV | Percentages of Subjects With Serum Bactericidal Titers ≥1:8 Following Concomitant Administration of MenACWY-CRM Vaccine With MMRV Vaccine. | Serogroup A | 88 Percentages of subjects |
| MMRV | Percentages of Subjects With Serum Bactericidal Titers ≥1:8 Following Concomitant Administration of MenACWY-CRM Vaccine With MMRV Vaccine. | Sergroup W-135 (N=204,196) | 98 Percentages of subjects |
| MMRV | Percentages of Subjects With Serum Bactericidal Titers ≥1:8 Following Concomitant Administration of MenACWY-CRM Vaccine With MMRV Vaccine. | Seroroup C (N=204,195) | 100 Percentages of subjects |
Comparison: Non-inferiority of immune response of MenACWY-CRM against serogroup A when concomitantly administered with MMRV vaccine as compared to MenACWY-CRM vaccine given alone.95% CI: [-4.7, 4.5]
Comparison: Non-inferiority of immune response of MenACWY-CRM against serogroup C when concomitantly administered with MMRV vaccine as compared to MenACWY-CRM vaccine given alone.95% CI: [-1.8, 1.9]
Comparison: Non-inferiority of immune response of MenACWY-CRM against serogroup W-135 when concomitantly administered with MMRV vaccine as compared to MenACWY vaccine given alone.95% CI: [-1.3, 3.9]
Comparison: Non-inferiority of immune response of MenACWY-CRM against serogroup Y when concomitantly administered with MMRV vaccine as compared to MenACWY-CRM vaccine given alone.95% CI: [-1.9, 5.3]
Secondary
Geometric Mean Titers After One Dose of MenACWY-CRM Vaccine
The immunogenicity of one dose of MenACWY-CRM vaccine given at 7 to 9 months of age was assessed in terms of GMTs directed against N.meningitidis serogroups A, C, W-135, and Y.
Time frame: 1 month post vaccine dose 1
Population: The analysis was performed on the MenACWY per-protocol population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MenACWY-CRM+ MMRV | Geometric Mean Titers After One Dose of MenACWY-CRM Vaccine | Serogroup A | 8.16 Titers |
| MenACWY-CRM+ MMRV | Geometric Mean Titers After One Dose of MenACWY-CRM Vaccine | Serogroup C (N=199) | 26 Titers |
| MenACWY-CRM+ MMRV | Geometric Mean Titers After One Dose of MenACWY-CRM Vaccine | Serogroup W-135 (N=199) | 5.11 Titers |
| MenACWY-CRM+ MMRV | Geometric Mean Titers After One Dose of MenACWY-CRM Vaccine | Serogroup Y (N=196) | 4.09 Titers |
Secondary
Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine.
The GMTs directed against measles, mumps, rubella and varicella, following one dose of MMRV vaccine (at 12 months) when given concomitantly with MenACWY-CRM vaccine compared to when MMRV vaccine was given alone, are reported.
Time frame: 6 weeks post vaccination
Population: The analysis was performed on the MMRV per-protocol population.~Only subjects with a baseline titer below the specified cut-off for that antigen were included in the immunogenicity analysis for the same antigen.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MenACWY-CRM+ MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Pre-dose, Measles (N=357,470) | 74 Titers |
| MenACWY-CRM+ MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Post-dose, Measles (N=350,467) | 4049 Titers |
| MenACWY-CRM+ MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Pre-dose, Mumps (N=372,502) | 5 Titers |
| MenACWY-CRM+ MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Post-dose, Mumps (N=365,499) | 97 Titers |
| MenACWY-CRM+ MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Pre-dose, Rubella | 5 Titers |
| MenACWY-CRM+ MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Post-dose, Rubella (N=370,515) | 57 Titers |
| MenACWY-CRM+ MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Pre-dose, Varicella (N=344,461) | 0.63 Titers |
| MenACWY-CRM+ MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Post-dose, Varicella (N=337,459) | 19 Titers |
| MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Post-dose, Varicella (N=337,459) | 18 Titers |
| MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Pre-dose, Measles (N=357,470) | 74 Titers |
| MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Pre-dose, Rubella | 5 Titers |
| MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Post-dose, Measles (N=350,467) | 3632 Titers |
| MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Pre-dose, Varicella (N=344,461) | 0.63 Titers |
| MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Pre-dose, Mumps (N=372,502) | 5 Titers |
| MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Post-dose, Rubella (N=370,515) | 56 Titers |
| MMRV | Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | Post-dose, Mumps (N=365,499) | 81 Titers |
Secondary
Geometric Mean Titers Against Serogroups A, C, W-135 and Y, Following Two Doses of MenACWY-CRM Vaccine
The geometric mean titers (GMTs) directed against N.meningitidis serogroups A, C, W-135 and Y, following two doses of MenACWY-CRM vaccine (at 7-9 months and 12 months of age), when given concomitantly with MMRV vaccine (at 12 months) compared to when MenACWY-CRM vaccine was given alone, are reported.
Time frame: 6 weeks post vaccine dose 2
Population: The analysis was performed on the MenACWY per-protocol population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MenACWY-CRM+ MMRV | Geometric Mean Titers Against Serogroups A, C, W-135 and Y, Following Two Doses of MenACWY-CRM Vaccine | Serogroup C (N=204,195) | 194 Titers |
| MenACWY-CRM+ MMRV | Geometric Mean Titers Against Serogroups A, C, W-135 and Y, Following Two Doses of MenACWY-CRM Vaccine | Serogroup A | 39 Titers |
| MenACWY-CRM+ MMRV | Geometric Mean Titers Against Serogroups A, C, W-135 and Y, Following Two Doses of MenACWY-CRM Vaccine | Serogroup W-135 (N=204,196) | 132 Titers |
| MenACWY-CRM+ MMRV | Geometric Mean Titers Against Serogroups A, C, W-135 and Y, Following Two Doses of MenACWY-CRM Vaccine | Serogroup Y (N=200,198) | 97 Titers |
| MMRV | Geometric Mean Titers Against Serogroups A, C, W-135 and Y, Following Two Doses of MenACWY-CRM Vaccine | Serogroup Y (N=200,198) | 88 Titers |
| MMRV | Geometric Mean Titers Against Serogroups A, C, W-135 and Y, Following Two Doses of MenACWY-CRM Vaccine | Serogroup W-135 (N=204,196) | 119 Titers |
| MMRV | Geometric Mean Titers Against Serogroups A, C, W-135 and Y, Following Two Doses of MenACWY-CRM Vaccine | Serogroup A | 37 Titers |
| MMRV | Geometric Mean Titers Against Serogroups A, C, W-135 and Y, Following Two Doses of MenACWY-CRM Vaccine | Serogroup C (N=204,195) | 180 Titers |
Secondary
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination
Safety and tolerability of MenACWY-CRM and MMRV vaccines when given concomitantly compared to when either MenACWY-CRM or MMRV vaccine was administered alone is reported in terms of the number of subjects with local and systemic adverse events after vaccination. Systemic reactions including axillary temperature reported during 28 days after vaccination at 12 months of age. These included the following systemic reactions: Measles-like rash, Rubella-like rash, Varicellalike rash, injection site rash, Mumps-like symptoms and axillary temperature.
Time frame: upto 7 days after any vaccination
Population: The analysis was performed on the safety set population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj.site Tenderness [MMRV (N=455,424,592)] | 105 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Injection(Inj.) site Tenderness [MenACWY-CRM] | 133 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj. site Erythema [MenACWY-CRM] | 153 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj.site Induration [ MenACWY-CRM] | 74 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Local Reactions | 278 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj.site Erythema [MMRV (N=456,425,593)] | 156 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj. site Induration [MMRV (456,424,593)] | 90 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Systemic Reactions | 371 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Rash (N=500,499,595) | 54 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Change in eating habits (N=475,483,550) | 132 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Sleepiness (N=500,499,595) | 219 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Persistent crying (N=475,483,550) | 135 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Irritability (N=500,500,595) | 273 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Vomiting (N=500,499,595) | 66 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Diarrhea (N=500,499,595) | 120 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Fever ( N=499,500,596) | 58 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Other | 208 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Analgesic.Antipyr.Meds (N=499,499,594) | 208 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Analgesic.Antipyr.Meds (N=499,499,594) | 254 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Local Reactions | 298 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Change in eating habits (N=475,483,550) | 136 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Irritability (N=500,500,595) | 298 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Injection(Inj.) site Tenderness [MenACWY-CRM] | 129 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Diarrhea (N=500,499,595) | 123 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Fever ( N=499,500,596) | 78 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj. site Erythema [MenACWY-CRM] | 159 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Sleepiness (N=500,499,595) | 199 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Other | 254 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj.site Induration [ MenACWY-CRM] | 74 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Rash (N=500,499,595) | 44 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Vomiting (N=500,499,595) | 74 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj.site Tenderness [MMRV (N=455,424,592)] | 102 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Systemic Reactions | 372 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Persistent crying (N=475,483,550) | 152 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj.site Erythema [MMRV (N=456,425,593)] | 145 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj. site Induration [MMRV (456,424,593)] | 60 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj.site Erythema [MMRV (N=456,425,593)] | 224 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj. site Induration [MMRV (456,424,593)] | 102 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Systemic Reactions | 381 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Diarrhea (N=500,499,595) | 107 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Rash (N=500,499,595) | 46 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Analgesic.Antipyr.Meds (N=499,499,594) | 203 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Change in eating habits (N=475,483,550) | 105 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Sleepiness (N=500,499,595) | 197 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Fever ( N=499,500,596) | 42 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Persistent crying (N=475,483,550) | 109 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Local Reactions | 316 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Injection(Inj.) site Tenderness [MenACWY-CRM] | 0 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Irritability (N=500,500,595) | 298 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj. site Erythema [MenACWY-CRM] | 0 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj.site Induration [ MenACWY-CRM] | 0 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Inj.site Tenderness [MMRV (N=455,424,592)] | 179 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Vomiting (N=500,499,595) | 36 Participants |
| MMRV | Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Other | 203 Participants |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events After Vaccination
The safety profile of MenACWY-CRM and MMRV vaccines when given concomitantly as compared to when MenACWY-CRM or MMRV was given alone is reported in terms of number of subjects reporting unsolicited adverse events (AEs), medically significant adverse events and serious adverse events (SAEs) after vaccination.
Time frame: Day 1- Day 180 (Through out the study)
Population: This analysis was done on the safety set population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination | SAEs | 18 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination | Any AE | 335 Participants |
| MenACWY-CRM+ MMRV | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination | At least probably related AEs | 70 Participants |
| MMRV | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination | Any AE | 311 Participants |
| MMRV | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination | At least probably related AEs | 2 Participants |
| MMRV | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination | SAEs | 9 Participants |
| MMRV | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination | SAEs | 19 Participants |
| MMRV | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination | At least probably related AEs | 63 Participants |
| MMRV | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination | Any AE | 353 Participants |
Secondary
Percentages of Subjects Showing Seroconversion Response to Varicella Following Concomitant Administration of MMRV With MenACWY-CRM Vaccine.
The percentages of subjects showing seroconversion response to varicella after concomitant administration of MMRV vaccine (at 12 months) with MenACWY-CRM vaccine compared to when MMRV vaccine is given alone, is reported . Seroconversion for varicella is defined as percentage of subjects who show pre-vaccination antibody titer \<1.25 gp ELISA units/mL to a post-vaccination antibody titer ≥1.25 gp ELISA units/mL.
Time frame: 6 weeks post vaccination
Population: The analysis was performed on the MMRV per-protocol population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MenACWY-CRM+ MMRV | Percentages of Subjects Showing Seroconversion Response to Varicella Following Concomitant Administration of MMRV With MenACWY-CRM Vaccine. | 99 Percentages of subjects |
| MMRV | Percentages of Subjects Showing Seroconversion Response to Varicella Following Concomitant Administration of MMRV With MenACWY-CRM Vaccine. | 99 Percentages of subjects |
Comparison: Non-inferiority of anti-varicella response following one dose of MMRV when administered concomitantly with MenACWY vaccine as compared to MMRV administered alone.95% CI: [-2.4, 0.8]
Secondary
Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine
The percentages of subjects with hSBA ≥1:4 directed against N. meningitidis serogroups A, C, W-135, and Y following two doses of MenACWY-CRM vaccine (at 7-9 and 12 months of age) when given concomitantly with MMRV vaccine (at 12 months) compared to when MenACWY-CRM vaccine was given alone, are reported.
Time frame: 6 weeks post vaccine dose 2
Population: The analysis was performed on the MenACWY per-protocol population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine | Serogroup A | 90 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine | Serogroup C (N=204,195) | 100 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine | Serogroup W-135 (N=204,196) | 100 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine | Serogroup Y (N=200,198) | 98 Percentages of subjects |
| MMRV | Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine | Serogroup Y (N=200,198) | 98 Percentages of subjects |
| MMRV | Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine | Serogroup A | 91 Percentages of subjects |
| MMRV | Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine | Serogroup W-135 (N=204,196) | 99 Percentages of subjects |
| MMRV | Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine | Serogroup C (N=204,195) | 100 Percentages of subjects |
Secondary
Percentages of Subjects With hSBA ≥1:4 and hSBA ≥1:8 Following One Dose of MenACWY-CRM Vaccine
The percentages of subjects with hSBA ≥1:4 and hSBA ≥1:8 after one dose of MenACWY-CRM vaccine (at 7-9 months), are reported
Time frame: 1 month post vaccine dose 1
Population: The analysis was performed on the MenACWY per-protocol population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:4 and hSBA ≥1:8 Following One Dose of MenACWY-CRM Vaccine | Serogroup A hSBA ≥1:4 | 63 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:4 and hSBA ≥1:8 Following One Dose of MenACWY-CRM Vaccine | Serogroup A hSBA ≥1:8 | 50 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:4 and hSBA ≥1:8 Following One Dose of MenACWY-CRM Vaccine | Serogroup C (N=199) hSBA ≥1:4 | 93 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:4 and hSBA ≥1:8 Following One Dose of MenACWY-CRM Vaccine | Serogroup C (N=199) hSBA ≥1:8 | 88 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:4 and hSBA ≥1:8 Following One Dose of MenACWY-CRM Vaccine | Serogroup W-135 (N=199) hSBA ≥1:4 | 48 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:4 and hSBA ≥1:8 Following One Dose of MenACWY-CRM Vaccine | Serogroup W-135 (N=199) hSBA ≥1:8 | 37 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:4 and hSBA ≥1:8 Following One Dose of MenACWY-CRM Vaccine | Serogroup Y (N=196) hSBA ≥1:4 | 41 Percentages of subjects |
| MenACWY-CRM+ MMRV | Percentages of Subjects With hSBA ≥1:4 and hSBA ≥1:8 Following One Dose of MenACWY-CRM Vaccine | Serogroup Y (N=196) hSBA ≥1:8 | 31 Percentages of subjects |