Trial Outcomes & Findings for Safety and Immune Response of Novartis MenACWY-CRM Conjugate Vaccine When Given to Healthy Toddlers (NCT NCT00626327)

Last Updated: 2013-04-19

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1630 participants

Primary outcome timeframe

6 weeks post vaccination

Results posted on

2013-04-19

Participant Flow

Participants were enrolled at 90 centers in the USA

All subjects enrolled were included in the trial.

Participant milestones

Participant milestones
Measure	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	MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	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
Overall Study STARTED	504	616	510
Overall Study COMPLETED	426	557	422
Overall Study NOT COMPLETED	78	59	88

Reasons for withdrawal

Reasons for withdrawal
Measure	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	MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	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
Overall Study Withdrawal by Subject	21	29	30
Overall Study Adverse Event	1	0	0
Overall Study Lost to Follow-up	24	21	23
Overall Study Inappropriate enrollment	4	5	3
Overall Study Administrative Reason	2	0	6
Overall Study Protocol Violation	26	4	26

Baseline Characteristics

Safety and Immune Response of Novartis MenACWY-CRM Conjugate Vaccine When Given to Healthy Toddlers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MenACWY-CRM+ MMRV n=504 Participants Subjects in this group received 2 injections of MenACWY-CRM at 7-9 and 12 months; second injection administered concomitantly with MMRV	MMRV n=616 Participants Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	MenACWY-CRM n=510 Participants 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	Total n=1630 Participants Total of all reporting groups
Age Continuous	8.5 months STANDARD_DEVIATION 0.8 • n=5 Participants	12.1 months STANDARD_DEVIATION 0.3 • n=7 Participants	8.5 months STANDARD_DEVIATION 0.8 • n=5 Participants	9.8 months STANDARD_DEVIATION 1.9 • n=4 Participants
Sex: Female, Male Female	251 Participants n=5 Participants	304 Participants n=7 Participants	252 Participants n=5 Participants	807 Participants n=4 Participants
Sex: Female, Male Male	253 Participants n=5 Participants	312 Participants n=7 Participants	258 Participants n=5 Participants	823 Participants n=4 Participants

PRIMARY outcome

Timeframe: 6 weeks post vaccination

Population: The analysis was performed on the MMRV per-protocol population

Outcome measures

Outcome measures
Measure	MenACWY-CRM+ MMRV n=370 Participants Subjects in this group received 2 injections of MenACWY-CRM at 7-9 and 12 months; second injection administered concomitantly with MMRV	MMRV n=515 Participants Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age
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 Interval 96.0 to 99.0	99 Percentages of subjects Interval 98.0 to 100.0	—
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 Interval 96.0 to 99.0	96 Percentages of subjects Interval 94.0 to 98.0	—
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 Interval 93.0 to 97.0	97 Percentages of subjects Interval 95.0 to 98.0	—
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 Interval 94.0 to 98.0	98 Percentages of subjects Interval 96.0 to 99.0	—

PRIMARY outcome

Timeframe: 6 weeks post second dose

Population: The analysis was performed on the MenACWY per-protocol population

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.

Outcome measures

Outcome measures
Measure	MenACWY-CRM+ MMRV n=384 Participants Subjects in this group received 2 injections of MenACWY-CRM at 7-9 and 12 months; second injection administered concomitantly with MMRV	MMRV n=379 Participants Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age
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 Interval 84.0 to 91.0	88 Percentages of subjects Interval 84.0 to 91.0	—
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 Interval 98.0 to 100.0	100 Percentages of subjects Interval 98.0 to 100.0	—
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 Interval 97.0 to 100.0	98 Percentages of subjects Interval 96.0 to 100.0	—
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 Interval 95.0 to 99.0	96 Percentages of subjects Interval 93.0 to 99.0	—

PRIMARY outcome

Timeframe: 6 weeks post vaccine dose 2

Population: The analysis was performed on the MenACWY per-protocol population

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.

Outcome measures

Outcome measures
Measure	MenACWY-CRM+ MMRV n=379 Participants Subjects in this group received 2 injections of MenACWY-CRM at 7-9 and 12 months; second injection administered concomitantly with MMRV	MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age
Percentages of Subjects With hSBA ≥1:8 Following Two Doses of MenACWY-CRM Vaccine Serogroup A	88 Percentages of subjects Interval 84.0 to 91.0	—	—
Percentages of Subjects With hSBA ≥1:8 Following Two Doses of MenACWY-CRM Vaccine Serogroup C (N=195)	100 Percentages of subjects Interval 98.0 to 100.0	—	—
Percentages of Subjects With hSBA ≥1:8 Following Two Doses of MenACWY-CRM Vaccine Serogroup W-135 (N=196)	98 Percentages of subjects Interval 96.0 to 100.0	—	—
Percentages of Subjects With hSBA ≥1:8 Following Two Doses of MenACWY-CRM Vaccine Serogroup Y (N=198)	96 Percentages of subjects Interval 93.0 to 99.0	—	—

SECONDARY outcome

Timeframe: 6 weeks post vaccine dose 2

Population: The analysis was performed on the MenACWY per-protocol population

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.

Outcome measures

Outcome measures
Measure	MenACWY-CRM+ MMRV n=384 Participants Subjects in this group received 2 injections of MenACWY-CRM at 7-9 and 12 months; second injection administered concomitantly with MMRV	MMRV n=379 Participants Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age
Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine Serogroup A	90 Percentages of subjects Interval 86.0 to 92.0	91 Percentages of subjects Interval 87.0 to 93.0	—
Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine Serogroup C (N=204,195)	100 Percentages of subjects Interval 98.0 to 100.0	100 Percentages of subjects Interval 98.0 to 100.0	—
Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine Serogroup W-135 (N=204,196)	100 Percentages of subjects Interval 97.0 to 100.0	99 Percentages of subjects Interval 96.0 to 100.0	—
Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine Serogroup Y (N=200,198)	98 Percentages of subjects Interval 95.0 to 99.0	98 Percentages of subjects Interval 95.0 to 99.0	—

SECONDARY outcome

Timeframe: 6 weeks post vaccine dose 2

Population: The analysis was performed on the MenACWY per-protocol population

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.

Outcome measures

Outcome measures
Measure	MenACWY-CRM+ MMRV n=384 Participants Subjects in this group received 2 injections of MenACWY-CRM at 7-9 and 12 months; second injection administered concomitantly with MMRV	MMRV n=379 Participants Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age
Geometric Mean Titers Against Serogroups A, C, W-135 and Y, Following Two Doses of MenACWY-CRM Vaccine Serogroup A	39 Titers Interval 34.0 to 45.0	37 Titers Interval 32.0 to 42.0	—
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 Interval 170.0 to 220.0	180 Titers Interval 158.0 to 205.0	—
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 Interval 81.0 to 116.0	88 Titers Interval 73.0 to 105.0	—
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 Interval 113.0 to 155.0	119 Titers Interval 101.0 to 139.0	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	MenACWY-CRM+ MMRV n=377 Participants Subjects in this group received 2 injections of MenACWY-CRM at 7-9 and 12 months; second injection administered concomitantly with MMRV	MMRV n=518 Participants Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age
Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. Post-dose, Mumps (N=365,499)	97 Titers Interval 89.0 to 107.0	81 Titers Interval 75.0 to 88.0	—
Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. Pre-dose, Rubella	5 Titers Interval 5.0 to 5.0	5 Titers Interval 5.0 to 5.0	—
Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. Pre-dose, Measles (N=357,470)	74 Titers Interval 71.0 to 77.0	74 Titers Interval 71.0 to 77.0	—
Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. Post-dose, Measles (N=350,467)	4049 Titers Interval 3701.0 to 4430.0	3632 Titers Interval 3350.0 to 3938.0	—
Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. Pre-dose, Mumps (N=372,502)	5 Titers Interval 5.0 to 5.0	5 Titers Interval 5.0 to 5.0	—
Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. Post-dose, Rubella (N=370,515)	57 Titers Interval 52.0 to 62.0	56 Titers Interval 52.0 to 61.0	—
Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. Pre-dose, Varicella (N=344,461)	0.63 Titers Interval 0.63 to 0.63	0.63 Titers Interval 0.63 to 0.63	—
Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. Post-dose, Varicella (N=337,459)	19 Titers Interval 17.0 to 20.0	18 Titers Interval 17.0 to 19.0	—

SECONDARY outcome

Timeframe: 6 weeks post vaccination

Population: The analysis was performed on the MMRV per-protocol population

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.

Outcome measures

Outcome measures
Measure	MenACWY-CRM+ MMRV n=337 Participants Subjects in this group received 2 injections of MenACWY-CRM at 7-9 and 12 months; second injection administered concomitantly with MMRV	MMRV n=459 Participants Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age
Percentages of Subjects Showing Seroconversion Response to Varicella Following Concomitant Administration of MMRV With MenACWY-CRM Vaccine.	99 Percentages of subjects Interval 97.0 to 100.0	99 Percentages of subjects Interval 98.0 to 100.0	—

SECONDARY outcome

Timeframe: 1 month post vaccine dose 1

Population: The analysis was performed on the MenACWY per-protocol population

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

Outcome measures

Outcome measures
Measure	MenACWY-CRM+ MMRV n=349 Participants Subjects in this group received 2 injections of MenACWY-CRM at 7-9 and 12 months; second injection administered concomitantly with MMRV	MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age
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 Interval 88.0 to 96.0	—	—
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 Interval 83.0 to 92.0	—	—
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 Interval 24.0 to 38.0	—	—
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 Interval 57.0 to 68.0	—	—
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 Interval 45.0 to 56.0	—	—
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 Interval 41.0 to 55.0	—	—
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 Interval 30.0 to 44.0	—	—
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 Interval 34.0 to 49.0	—	—

SECONDARY outcome

Timeframe: 1 month post vaccine dose 1

Population: The analysis was performed on the MenACWY per-protocol population

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.

Outcome measures

Outcome measures
Measure	MenACWY-CRM+ MMRV n=349 Participants Subjects in this group received 2 injections of MenACWY-CRM at 7-9 and 12 months; second injection administered concomitantly with MMRV	MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	MMRV Subjects in this group received 1 injection of MMRV vaccine at 12 months of age
Geometric Mean Titers After One Dose of MenACWY-CRM Vaccine Serogroup A	8.16 Titers Interval 6.96 to 9.58	—	—
Geometric Mean Titers After One Dose of MenACWY-CRM Vaccine Serogroup C (N=199)	26 Titers Interval 22.0 to 31.0	—	—
Geometric Mean Titers After One Dose of MenACWY-CRM Vaccine Serogroup W-135 (N=199)	5.11 Titers Interval 4.15 to 6.29	—	—
Geometric Mean Titers After One Dose of MenACWY-CRM Vaccine Serogroup Y (N=196)	4.09 Titers Interval 3.36 to 4.98	—	—

SECONDARY outcome

Timeframe: upto 7 days after any vaccination

Population: The analysis was performed on the safety set population

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.

Outcome measures

Outcome measures
Measure	MenACWY-CRM+ MMRV n=500 Participants Subjects in this group received 2 injections of MenACWY-CRM at 7-9 and 12 months; second injection administered concomitantly with MMRV	MMRV n=500 Participants Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	MMRV n=597 Participants Subjects in this group received 1 injection of MMRV vaccine at 12 months of age
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Injection(Inj.) site Tenderness [MenACWY-CRM]	133 Participants	129 Participants	0 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Inj. site Erythema [MenACWY-CRM]	153 Participants	159 Participants	0 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Inj.site Induration [ MenACWY-CRM]	74 Participants	74 Participants	0 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Local Reactions	278 Participants	298 Participants	316 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Inj.site Tenderness [MMRV (N=455,424,592)]	105 Participants	102 Participants	179 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Inj.site Erythema [MMRV (N=456,425,593)]	156 Participants	145 Participants	224 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Inj. site Induration [MMRV (456,424,593)]	90 Participants	60 Participants	102 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Systemic Reactions	371 Participants	372 Participants	381 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Rash (N=500,499,595)	54 Participants	44 Participants	46 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Change in eating habits (N=475,483,550)	132 Participants	136 Participants	105 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Sleepiness (N=500,499,595)	219 Participants	199 Participants	197 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Persistent crying (N=475,483,550)	135 Participants	152 Participants	109 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Irritability (N=500,500,595)	273 Participants	298 Participants	298 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Vomiting (N=500,499,595)	66 Participants	74 Participants	36 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Diarrhea (N=500,499,595)	120 Participants	123 Participants	107 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Fever ( N=499,500,596)	58 Participants	78 Participants	42 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Other	208 Participants	254 Participants	203 Participants
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination Analgesic.Antipyr.Meds (N=499,499,594)	208 Participants	254 Participants	203 Participants

SECONDARY outcome

Timeframe: Day 1- Day 180 (Through out the study)

Population: This analysis was done on the safety set population

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.

Outcome measures

Outcome measures
Measure	MenACWY-CRM+ MMRV n=500 Participants Subjects in this group received 2 injections of MenACWY-CRM at 7-9 and 12 months; second injection administered concomitantly with MMRV	MMRV n=597 Participants Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	MMRV n=500 Participants Subjects in this group received 1 injection of MMRV vaccine at 12 months of age
Number of Subjects Reporting Unsolicited Adverse Events After Vaccination Any AE	335 Participants	311 Participants	353 Participants
Number of Subjects Reporting Unsolicited Adverse Events After Vaccination At least probably related AEs	70 Participants	2 Participants	63 Participants
Number of Subjects Reporting Unsolicited Adverse Events After Vaccination SAEs	18 Participants	9 Participants	19 Participants

Adverse Events

MenACWY-CRM+ MMRV

Serious events: 18 serious events

Other events: 433 other events

Deaths: 0 deaths

MMRV

Serious events: 9 serious events

Other events: 482 other events

Deaths: 0 deaths

MenACWY-CRM

Serious events: 19 serious events

Other events: 442 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Posting Director

Novartis Vaccines and Diagnostics

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	MenACWY-CRM+ MMRV n=500 participants at risk Subjects in this group received 2 injections of MenACWY-CRM at 7-9 and 12 months; second injection administered concomitantly with MMRV	MMRV n=597 participants at risk Subjects in this group received 1 injection of MMRV vaccine at 12 months of age	MenACWY-CRM n=500 participants at risk 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
Gastrointestinal disorders Diarrhoea	25.0% 125/500 • Number of events 125 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	19.1% 114/597 • Number of events 114 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	25.6% 128/500 • Number of events 128 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).
Gastrointestinal disorders Teething	8.2% 41/500 • Number of events 41 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	6.9% 41/597 • Number of events 41 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	12.0% 60/500 • Number of events 60 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).
Gastrointestinal disorders Vomiting	13.6% 68/500 • Number of events 68 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	7.2% 43/597 • Number of events 43 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	15.8% 79/500 • Number of events 79 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).
General disorders Injection site erythema	43.8% 219/500 • Number of events 219 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	37.5% 224/597 • Number of events 224 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	46.0% 230/500 • Number of events 230 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).
General disorders Injection site induration	25.6% 128/500 • Number of events 128 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	17.1% 102/597 • Number of events 102 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	23.0% 115/500 • Number of events 115 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).
General disorders Injection site pain	32.6% 163/500 • Number of events 163 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	30.2% 180/597 • Number of events 180 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	37.6% 188/500 • Number of events 188 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).
General disorders Irritability	54.6% 273/500 • Number of events 273 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	50.1% 299/597 • Number of events 299 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	59.8% 299/500 • Number of events 299 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).
General disorders Pyrexia	18.0% 90/500 • Number of events 90 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	11.7% 70/597 • Number of events 70 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	22.8% 114/500 • Number of events 114 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).
Infections and infestations Otitis media	18.4% 92/500 • Number of events 92 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	6.7% 40/597 • Number of events 40 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	24.0% 120/500 • Number of events 120 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).
Infections and infestations Upper respiratory tract infection	14.2% 71/500 • Number of events 71 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	3.4% 20/597 • Number of events 20 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	18.4% 92/500 • Number of events 92 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).
Nervous system disorders Crying	27.0% 135/500 • Number of events 135 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	18.3% 109/597 • Number of events 109 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	30.4% 152/500 • Number of events 152 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).
Nervous system disorders Somnolence	43.8% 219/500 • Number of events 219 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	33.0% 197/597 • Number of events 197 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	39.8% 199/500 • Number of events 199 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).
Psychiatric disorders Eating disorder	26.4% 132/500 • Number of events 132 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	17.6% 105/597 • Number of events 105 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	27.2% 136/500 • Number of events 136 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).
Skin and subcutaneous tissue disorders Dermatitis diaper	5.2% 26/500 • Number of events 26 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	4.9% 29/597 • Number of events 29 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	6.0% 30/500 • Number of events 30 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).
Skin and subcutaneous tissue disorders Rash	15.2% 76/500 • Number of events 76 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	14.6% 87/597 • Number of events 87 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).	10.4% 52/500 • Number of events 52 • All solicited adverse events (AEs) were collected upto Day 7 after each vaccination. All SAEs and unsolicited AEs were collected throughout the study (Day 1-Day 180).