Trial Outcomes & Findings for Safety and Immunogenicity of Different Meningitis Vaccine Formulations in Adolescents and Young Adults (NCT NCT01272180)

Last Updated: 2020-06-16

Results Overview

Non-inferiority of immune response of two doses of two different formulations of MenABCWY vaccine to a single dose of MenACWY vaccine as measured by the percentage of subjects with hSBA seroresponse against N.meningitidis serogroups A,C,W and Y. Seroresponse is defined as: 1. For subjects with a pre-vaccination hSBA titer \< 1:4, a post-vaccination hSBA titer ≥ 1:8; 2. For subjects with a pre-vaccination hSBA titer ≥ 1:4, an increase in hSBA titer of at least four times the prevaccination titer. Functional bactericidal antibodies directed against serogroups A,C,W,Y meningococci were measured with a serum bactericidal activity assay using human serum as the source of exogenous complement (hSBA).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

484 participants

Primary outcome timeframe

One month after the second vaccination (Day 91)

Results posted on

2020-06-16

Participant Flow

All enrolled subjects were included in the trial.

Participant milestones

Participant milestones
Measure	ABCWY+OMV Subjects in this group received two doses of ABCWY+OMV combination vaccine, administered two months apart.	ABCWY+qOMV Subjects in this group received two doses of ABCWY+qOMV combination vaccine, administered two months apart.	rMenB +OMV Subjects in this group received two doses of rMenB + OMV vaccine,administered two months apart.	ACWY Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.
Overall Study STARTED	120	121	122	121
Overall Study COMPLETED	103	100	109	107
Overall Study NOT COMPLETED	17	21	13	14

Reasons for withdrawal

Reasons for withdrawal
Measure	ABCWY+OMV Subjects in this group received two doses of ABCWY+OMV combination vaccine, administered two months apart.	ABCWY+qOMV Subjects in this group received two doses of ABCWY+qOMV combination vaccine, administered two months apart.	rMenB +OMV Subjects in this group received two doses of rMenB + OMV vaccine,administered two months apart.	ACWY Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.
Overall Study Adverse Event	0	0	1	0
Overall Study Withdrawal by Subject	2	6	3	2
Overall Study Lost to Follow-up	15	14	8	10
Overall Study Inappropriate enrollment	0	0	1	1
Overall Study Protocol Violation	0	1	0	1

Baseline Characteristics

Safety and Immunogenicity of Different Meningitis Vaccine Formulations in Adolescents and Young Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ABCWY+OMV n=120 Participants Subjects in this group received two doses of ABCWY+OMV combination vaccine, administered two months apart.	ABCWY+qOMV n=121 Participants Subjects in this group received two doses of ABCWY+qOMV combination vaccine, administered two months apart.	rMenB +OMV n=122 Participants Subjects in this group received two doses of rMenB + OMV vaccine,administered two months apart.	ACWY n=121 Participants Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.	Total n=484 Participants Total of all reporting groups
Age, Continuous	14.7 years STANDARD_DEVIATION 4.7 • n=93 Participants	15.1 years STANDARD_DEVIATION 4.9 • n=4 Participants	15.3 years STANDARD_DEVIATION 4.9 • n=27 Participants	15.0 years STANDARD_DEVIATION 5.1 • n=483 Participants	15.0 years STANDARD_DEVIATION 4.9 • n=36 Participants
Sex: Female, Male Female	61 Participants n=93 Participants	68 Participants n=4 Participants	60 Participants n=27 Participants	64 Participants n=483 Participants	253 Participants n=36 Participants
Sex: Female, Male Male	59 Participants n=93 Participants	53 Participants n=4 Participants	62 Participants n=27 Participants	57 Participants n=483 Participants	231 Participants n=36 Participants

PRIMARY outcome

Timeframe: One month after the second vaccination (Day 91)

Population: Analysis was done on the per protocol population, immunogenicity, i.e subjects who received correct vaccines in both the visits; provided evaluable serum sample pre and post vaccination with assay results available for at least one serogroup and/or strain and had no major protocol violations.

Outcome measures

Outcome measures
Measure	ABCWY+OMV n=88 Participants Subjects in this group received two doses of ABCWY+OMV combination vaccine, administered two months apart.	ABCWY+qOMV n=84 Participants Subjects in this group received two doses of ABCWY+qOMV combination vaccine, administered two months apart.	ACWY n=76 Participants Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.	ACWY Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.
Percentages of Subjects With a Seroresponse Against N.Meningitidis Serogroups A,C,W-135,Y, After Receiving Different Formulations of MenABCWY Combination Vaccine. Men W-135	80 Percentages of subjects Interval 69.0 to 88.0	84 Percentages of subjects Interval 73.0 to 91.0	65 Percentages of subjects Interval 52.0 to 77.0	—
Percentages of Subjects With a Seroresponse Against N.Meningitidis Serogroups A,C,W-135,Y, After Receiving Different Formulations of MenABCWY Combination Vaccine. Men A	90 Percentages of subjects Interval 81.0 to 95.0	92 Percentages of subjects Interval 83.0 to 97.0	73 Percentages of subjects Interval 62.0 to 83.0	—
Percentages of Subjects With a Seroresponse Against N.Meningitidis Serogroups A,C,W-135,Y, After Receiving Different Formulations of MenABCWY Combination Vaccine. Men C	95 Percentages of subjects Interval 89.0 to 99.0	93 Percentages of subjects Interval 85.0 to 97.0	63 Percentages of subjects Interval 51.0 to 74.0	—
Percentages of Subjects With a Seroresponse Against N.Meningitidis Serogroups A,C,W-135,Y, After Receiving Different Formulations of MenABCWY Combination Vaccine. Men Y	92 Percentages of subjects Interval 83.0 to 97.0	90 Percentages of subjects Interval 80.0 to 96.0	75 Percentages of subjects Interval 62.0 to 85.0	—

PRIMARY outcome

Timeframe: One month after the second vaccination (Day 91)

Population: Analysis was done on the Per Protocol Set - desirability, ie, all subjects who : correctly received the vaccine at Visit 1 and Visit 2, provided evaluable serum samples pre- (Visit 1) and post-vaccination (Visit 3), provided post-vaccination solicited adverse event data an had no major protocol violation as defined prior to unblinding.

The overall desirability index (DI) used to identify the optimal formulation of the combination vaccine was based on immunogenicity and reactogenicity parameters (on a scale of 0 to 1, with 0 for an undesirable response and 1 for a highly desirable response) as follows: Between-group ratios of hSBA GMTs were calculated, adjusted for prevaccination titer and center, against serogroups A, C, W, and Y (ABCWY+OMV group or ABCWY+qOMV group vs. Placebo/ACWY group) and against the 4 serogroup B test strains (ABCWY+OMV group or ABCWY+qOMV group vs. rMenB+OMV group). Reactogenicity was measured by the percentage of doses associated with severe local and systemic solicited AEs within 3 days following vaccination. Each immunogenicity and reactogenicity endpoint was assigned its own DI based on predefined desirability functions. The overall DI was calculated using the weighted geometric mean of the DI values of each of the ten parameters to derive an overall DI for each formulation.

Outcome measures

Outcome measures
Measure	ABCWY+OMV n=86 Participants Subjects in this group received two doses of ABCWY+OMV combination vaccine, administered two months apart.	ABCWY+qOMV n=82 Participants Subjects in this group received two doses of ABCWY+qOMV combination vaccine, administered two months apart.	ACWY Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.	ACWY Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.
Desirability Index for Each Vaccine Group, Based on Immunogenicity and Reactogenicity Parameters.	0.306 Desirability index	0.325 Desirability index	—	—

SECONDARY outcome

Timeframe: Day 1 and one month after second vaccination (Day 91)

Population: Analysis was done on the per protocol population, immunogenicity.

Percentages of subjects with hSBA titers ≥ 1:8 against N.meningitidis serogroups A,C,W-135 and Y, after two doses of either ABCWY+OMV or ABCWY+qOMV combination vaccine or one dose of MenACWY vaccine.

Outcome measures

Outcome measures
Measure	ABCWY+OMV n=90 Participants Subjects in this group received two doses of ABCWY+OMV combination vaccine, administered two months apart.	ABCWY+qOMV n=85 Participants Subjects in this group received two doses of ABCWY+qOMV combination vaccine, administered two months apart.	ACWY n=76 Participants Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.	ACWY Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.
Percentages of Subjects With hSBA Titers ≥ 1:8 Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men A (Day 1)	8 Percentages of subjects Interval 3.0 to 15.0	6 Percentages of subjects Interval 2.0 to 13.0	1 Percentages of subjects Interval 0.033 to 7.0	—
Percentages of Subjects With hSBA Titers ≥ 1:8 Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men A (Day 91)	93 Percentages of subjects Interval 86.0 to 97.0	95 Percentages of subjects Interval 88.0 to 99.0	73 Percentages of subjects Interval 62.0 to 83.0	—
Percentages of Subjects With hSBA Titers ≥ 1:8 Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men W-135 (Day 1)	66 Percentages of subjects Interval 55.0 to 76.0	58 Percentages of subjects Interval 47.0 to 69.0	51 Percentages of subjects Interval 39.0 to 64.0	—
Percentages of Subjects With hSBA Titers ≥ 1:8 Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men C (Day 1)	35 Percentages of subjects Interval 25.0 to 46.0	35 Percentages of subjects Interval 25.0 to 46.0	32 Percentages of subjects Interval 21.0 to 43.0	—
Percentages of Subjects With hSBA Titers ≥ 1:8 Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men C (Day 91)	99 Percentages of subjects Interval 94.0 to 100.0	100 Percentages of subjects Interval 96.0 to 100.0	83 Percentages of subjects Interval 73.0 to 91.0	—
Percentages of Subjects With hSBA Titers ≥ 1:8 Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men W-135 (Day 91)	100 Percentages of subjects Interval 95.0 to 100.0	100 Percentages of subjects Interval 95.0 to 100.0	89 Percentages of subjects Interval 79.0 to 96.0	—
Percentages of Subjects With hSBA Titers ≥ 1:8 Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men Y (Day 1)	18 Percentages of subjects Interval 11.0 to 28.0	15 Percentages of subjects Interval 8.0 to 25.0	8 Percentages of subjects Interval 3.0 to 17.0	—
Percentages of Subjects With hSBA Titers ≥ 1:8 Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men Y (Day 91)	97 Percentages of subjects Interval 89.0 to 100.0	97 Percentages of subjects Interval 90.0 to 100.0	82 Percentages of subjects Interval 70.0 to 90.0	—

SECONDARY outcome

Timeframe: Day 1 and one month after the second vaccination (Day 91)

Population: Analysis was done on the per protocol population, immunogenicity.

The hSBA GMTs against N.meningitidis serogroups A,C,W-135 and Y, after two doses of either ABCWY+OMV or ABCWY+qOMV combination vaccine, or one dose of MenACWY vaccine.

Outcome measures

Outcome measures
Measure	ABCWY+OMV n=90 Participants Subjects in this group received two doses of ABCWY+OMV combination vaccine, administered two months apart.	ABCWY+qOMV n=85 Participants Subjects in this group received two doses of ABCWY+qOMV combination vaccine, administered two months apart.	ACWY n=76 Participants Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.	ACWY Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.
The hSBA GMTs Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men A (Day 1)	1.57 Titers Interval 1.28 to 1.92	1.32 Titers Interval 1.07 to 1.63	1.33 Titers Interval 1.08 to 1.65	—
The hSBA GMTs Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men A (Day 91)	71 Titers Interval 49.0 to 102.0	77 Titers Interval 53.0 to 111.0	45 Titers Interval 31.0 to 65.0	—
The hSBA GMTs Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men C (Day 1)	4.15 Titers Interval 3.02 to 5.69	3.72 Titers Interval 2.69 to 5.12	3.93 Titers Interval 2.84 to 5.45	—
The hSBA GMTs Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men C (Day 91)	214 Titers Interval 148.0 to 309.0	187 Titers Interval 129.0 to 272.0	55 Titers Interval 38.0 to 80.0	—
The hSBA GMTs Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men W-135 (Day 1)	14 Titers Interval 8.88 to 22.0	10 Titers Interval 6.45 to 16.0	6.58 Titers Interval 4.11 to 11.0	—
The hSBA GMTs Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men W-135 (Day 91)	239 Titers Interval 178.0 to 322.0	288 Titers Interval 214.0 to 389.0	65 Titers Interval 48.0 to 90.0	—
The hSBA GMTs Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men Y (Day 1)	2.01 Titers Interval 1.52 to 2.66	1.91 Titers Interval 1.43 to 2.53	1.52 Titers Interval 1.14 to 2.04	—
The hSBA GMTs Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. Men Y (Day 91)	149 Titers Interval 95.0 to 234.0	129 Titers Interval 83.0 to 201.0	46 Titers Interval 29.0 to 72.0	—

SECONDARY outcome

Timeframe: Day 1 and one month after the second vaccination (Day 91)

Population: Analysis was done on the per-protocol population, immunogenicity

The percentages of subjects with hSBA titers ≥ 1:5 and ≥ 1:8 against four different strains of N.meningitidis serogroup B, after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV vaccine.

Outcome measures

Outcome measures
Measure	ABCWY+OMV n=90 Participants Subjects in this group received two doses of ABCWY+OMV combination vaccine, administered two months apart.	ABCWY+qOMV n=85 Participants Subjects in this group received two doses of ABCWY+qOMV combination vaccine, administered two months apart.	ACWY n=92 Participants Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.	ACWY Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.
Percentages of Subjects With hSBA Titers ≥ 1:5 and ≥ 1:8 Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M14459 (Day 1; hSBA ≥1:5)	9 Percentages of subjects Interval 4.0 to 17.0	4 Percentages of subjects Interval 1.0 to 10.0	5 Percentages of subjects Interval 2.0 to 12.0	—
Percentages of Subjects With hSBA Titers ≥ 1:5 and ≥ 1:8 Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M14459 (Day 91; hSBA ≥1:5)	64 Percentages of subjects Interval 53.0 to 74.0	71 Percentages of subjects Interval 60.0 to 80.0	82 Percentages of subjects Interval 72.0 to 89.0	—
Percentages of Subjects With hSBA Titers ≥ 1:5 and ≥ 1:8 Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M01-0240364 (Day 1; hSBA ≥1:5)	3 Percentages of subjects Interval 1.0 to 9.0	14 Percentages of subjects Interval 8.0 to 24.0	4 Percentages of subjects Interval 1.0 to 11.0	—
Percentages of Subjects With hSBA Titers ≥ 1:5 and ≥ 1:8 Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M01-0240364 (Day 91; hSBA ≥1:5)	80 Percentages of subjects Interval 70.0 to 88.0	80 Percentages of subjects Interval 70.0 to 88.0	93 Percentages of subjects Interval 86.0 to 98.0	—
Percentages of Subjects With hSBA Titers ≥ 1:5 and ≥ 1:8 Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. NZ 98/254 (Day 1; hSBA ≥1:5)	3 Percentages of subjects Interval 1.0 to 10.0	1 Percentages of subjects Interval 0.03 to 6.0	3 Percentages of subjects Interval 1.0 to 9.0	—

SECONDARY outcome

Timeframe: One month after the second vaccination (Day 91)

Population: Analysis was done on the per-protocol population, immunogenicity.

The percentages of subjects with at least 4-fold increase in hSBA titers against four different strains of N.meningitidis serogroup B, after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV vaccine. 4-fold increase is defined as follows; for subjects with a prevaccination hSBA \< 1:2, a postvaccination hSBA ≥ 1:8, for subjects with a prevaccination hSBA ≥ 1:2, at least a 4-fold increase.

Outcome measures

Outcome measures
Measure	ABCWY+OMV n=89 Participants Subjects in this group received two doses of ABCWY+OMV combination vaccine, administered two months apart.	ABCWY+qOMV n=85 Participants Subjects in this group received two doses of ABCWY+qOMV combination vaccine, administered two months apart.	ACWY n=92 Participants Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.	ACWY Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.
Percentages of Subjects With at Least 4-fold Increase in hSBA Titers Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M01-0240364	79 Percentages of subjects Interval 69.0 to 87.0	70 Percentages of subjects Interval 59.0 to 79.0	88 Percentages of subjects Interval 79.0 to 94.0	—
Percentages of Subjects With at Least 4-fold Increase in hSBA Titers Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M14459	56 Percentages of subjects Interval 45.0 to 67.0	62 Percentages of subjects Interval 51.0 to 73.0	75 Percentages of subjects Interval 65.0 to 83.0	—
Percentages of Subjects With at Least 4-fold Increase in hSBA Titers Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. NZ98/254	47 Percentages of subjects Interval 36.0 to 58.0	48 Percentages of subjects Interval 37.0 to 59.0	76 Percentages of subjects Interval 66.0 to 84.0	—
Percentages of Subjects With at Least 4-fold Increase in hSBA Titers Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M07-0241084	28 Percentages of subjects Interval 19.0 to 38.0	25 Percentages of subjects Interval 16.0 to 36.0	42 Percentages of subjects Interval 32.0 to 53.0	—

SECONDARY outcome

Timeframe: Day 1 and one month after the second vaccination (Day 91)

Population: Analysis was done on the per-protocol population, immunogenicity.

The hSBA GMTs against N.meningitidis serogroup B after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV vaccine.

Outcome measures

Outcome measures
Measure	ABCWY+OMV n=90 Participants Subjects in this group received two doses of ABCWY+OMV combination vaccine, administered two months apart.	ABCWY+qOMV n=85 Participants Subjects in this group received two doses of ABCWY+qOMV combination vaccine, administered two months apart.	ACWY n=92 Participants Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.	ACWY Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.
The hSBA GMTs Against N.Meningitidis serogroupB, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M14459 (Day 1)	1.32 Titers Interval 1.09 to 1.59	1.15 Titers Interval 0.95 to 1.4	1.26 Titers Interval 1.04 to 1.53	—
The hSBA GMTs Against N.Meningitidis serogroupB, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M14459 (Day 91)	9.24 Titers Interval 6.19 to 14.0	11 Titers Interval 7.51 to 17.0	17 Titers Interval 11.0 to 25.0	—
The hSBA GMTs Against N.Meningitidis serogroupB, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M01-0240364 (Day 1)	1.08 Titers Interval 0.82 to 1.42	1.72 Titers Interval 1.29 to 2.28	1.14 Titers Interval 0.86 to 1.51	—
The hSBA GMTs Against N.Meningitidis serogroupB, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M01-0240364 (Day 91)	55 Titers Interval 33.0 to 93.0	48 Titers Interval 28.0 to 83.0	118 Titers Interval 69.0 to 202.0	—
The hSBA GMTs Against N.Meningitidis serogroupB, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. NZ 98/254 (Day 1)	1.2 Titers Interval 1.03 to 1.39	1.1 Titers Interval 0.94 to 1.28	1.21 Titers Interval 1.04 to 1.42	—
The hSBA GMTs Against N.Meningitidis serogroupB, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. NZ 98/254 (Day 91)	8.68 Titers Interval 5.91 to 13.0	7.88 Titers Interval 5.3 to 12.0	19 Titers Interval 13.0 to 27.0	—
The hSBA GMTs Against N.Meningitidis serogroupB, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M07-0241084 (Day 1)	2.55 Titers Interval 1.86 to 3.49	2.45 Titers Interval 1.76 to 3.4	2.13 Titers Interval 1.54 to 2.94	—
The hSBA GMTs Against N.Meningitidis serogroupB, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M07-0241084 (Day 91)	7.24 Titers Interval 5.4 to 9.71	6.26 Titers Interval 4.63 to 8.46	12 Titers Interval 8.83 to 16.0	—

SECONDARY outcome

Timeframe: One month after the second vaccination/prevaccination (Day 91/day 1)

Population: Analysis was done on the per-protocol population

The geometric mean ratio (GMR) of post vaccination versus pre vaccination GMTs against N.meningitidis serogroup B after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV vaccine.

Outcome measures

Outcome measures
Measure	ABCWY+OMV n=89 Participants Subjects in this group received two doses of ABCWY+OMV combination vaccine, administered two months apart.	ABCWY+qOMV n=85 Participants Subjects in this group received two doses of ABCWY+qOMV combination vaccine, administered two months apart.	ACWY n=92 Participants Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.	ACWY Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.
The Geometric Mean Ratio of Post vs Pre Vaccination GMTs Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M14459	7.32 Ratio Interval 4.89 to 11.0	9.41 Ratio Interval 6.19 to 14.0	14 Ratio Interval 9.01 to 21.0	—
The Geometric Mean Ratio of Post vs Pre Vaccination GMTs Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M01-0240364	48 Ratio Interval 27.0 to 83.0	30 Ratio Interval 17.0 to 54.0	98 Ratio Interval 56.0 to 173.0	—
The Geometric Mean Ratio of Post vs Pre Vaccination GMTs Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. NZ 98/254	7.44 Ratio Interval 5.06 to 11.0	6.91 Ratio Interval 4.64 to 10.0	16 Ratio Interval 11.0 to 23.0	—
The Geometric Mean Ratio of Post vs Pre Vaccination GMTs Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. M07-0241084	2.94 Ratio Interval 2.15 to 4.02	2.59 Ratio Interval 1.88 to 3.58	5.16 Ratio Interval 3.76 to 7.08	—

SECONDARY outcome

Timeframe: Day 1 through day 7 after any vaccination

Population: Analysis was done on the solicited safety set, ie all subjects in the all exposed set who provided postvaccination solicited AE data from day 1 (6 hours) through day 7. The all exposed set is defined as all subjects in the all enrolled population who actually received a study vaccination.

The number of subjects reporting solicited local and systemic adverse events and other indicators of reactogenicity after vaccination with ABCWY+OMV, ABCWY+qOMV or rMenB+OMV or MenACWY.

Outcome measures

Outcome measures
Measure	ABCWY+OMV n=108 Participants Subjects in this group received two doses of ABCWY+OMV combination vaccine, administered two months apart.	ABCWY+qOMV n=110 Participants Subjects in this group received two doses of ABCWY+qOMV combination vaccine, administered two months apart.	ACWY n=115 Participants Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.	ACWY n=99 Participants Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Headache	37 Participants	40 Participants	53 Participants	29 Participants
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Rash	6 Participants	8 Participants	4 Participants	6 Participants
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Loss of appetite	17 Participants	22 Participants	24 Participants	12 Participants
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Fever ( >= 38C )	7 Participants	5 Participants	6 Participants	1 Participants
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Medically attended fever	2 Participants	0 Participants	0 Participants	0 Participants
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Prophylactic use of antipyretic	17 Participants	14 Participants	16 Participants	7 Participants
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Therapeutic use of antipyretic	18 Participants	26 Participants	27 Participants	10 Participants
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Injection site induration	46 Participants	52 Participants	46 Participants	24 Participants
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Injection site erythema	57 Participants	53 Participants	72 Participants	30 Participants
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Injection site pain	98 Participants	96 Participants	107 Participants	50 Participants
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Chills	18 Participants	21 Participants	29 Participants	12 Participants
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Nausea	15 Participants	25 Participants	30 Participants	8 Participants
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Fatigue	32 Participants	47 Participants	52 Participants	30 Participants
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Myalgia	65 Participants	67 Participants	67 Participants	38 Participants
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study. Arthralgia	20 Participants	23 Participants	25 Participants	7 Participants

SECONDARY outcome

Timeframe: Throughout the study ( Day 1 to Day 241)

Population: Analysis was done on the unsolicited safety set, ie, all subjects in the all exposed set who provided postvaccination unsolicited AE data.

The number of subjects reporting unsolicited AEs after vaccination with ABCWY+OMV, ABCWY+qOMV, rMenB+OMV or MenACWY.

Outcome measures

Outcome measures
Measure	ABCWY+OMV n=120 Participants Subjects in this group received two doses of ABCWY+OMV combination vaccine, administered two months apart.	ABCWY+qOMV n=120 Participants Subjects in this group received two doses of ABCWY+qOMV combination vaccine, administered two months apart.	ACWY n=120 Participants Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.	ACWY n=109 Participants Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study. Any AEs (from day 1 to 30)	36 Participants	36 Participants	45 Participants	31 Participants
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study. At least possibly related AEs (day 1 to 30)	12 Participants	10 Participants	16 Participants	6 Participants
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study. Any AEs (day 31 to 60 or study termination)	22 Participants	29 Participants	29 Participants	26 Participants
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study. At least poss.rel.AEs(day 31 to 60 or study term.)	0 Participants	1 Participants	0 Participants	0 Participants
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study. Any AE from day 1 to 91	51 Participants	55 Participants	66 Participants	50 Participants
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study. At least poss.rel.AEs(day 1 to 91)	13 Participants	10 Participants	16 Participants	6 Participants
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study. Medically attended AEs (day 92 to 241)	26 Participants	24 Participants	30 Participants	31 Participants
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study. possibly related med.attend.AEs (day 92-241)	0 Participants	0 Participants	0 Participants	0 Participants
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study. SAEs (Day 1 to Day 241)	2 Participants	2 Participants	1 Participants	3 Participants
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study. Possibly/probably related SAEs	0 Participants	0 Participants	0 Participants	0 Participants
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study. AEs leading to withdrawal (Day 1 to Day 241)	0 Participants	0 Participants	2 Participants	0 Participants
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study. Deaths (Day 1 to Day 241)	0 Participants	0 Participants	0 Participants	0 Participants

POST_HOC outcome

Timeframe: At baseline and one month after second vaccination (Day 91)

Population: Analysis was done on the per-protocol population, immunogenicity. This exploratory analysis was performed only on strains 44/76 and 5/99.

Percentages of Subjects With hSBA Titers ≥ 1:5 Against N.Meningitidis Serogroup B strains 44/76 and 5/99 at one month after second vaccination are calculated

Outcome measures

Outcome measures
Measure	ABCWY+OMV n=89 Participants Subjects in this group received two doses of ABCWY+OMV combination vaccine, administered two months apart.	ABCWY+qOMV n=85 Participants Subjects in this group received two doses of ABCWY+qOMV combination vaccine, administered two months apart.	ACWY n=92 Participants Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.	ACWY Subjects in this group received one dose of placebo followed by one dose of MenACWY vaccine two months later.
Percentages of Subjects With hSBA Titers ≥ 1:5 Against N.Meningitidis Serogroup B Strains 44/76 and 5/99 44/76- Baseline	6 Percentage of subjects Interval 2.0 to 12.0	7 Percentage of subjects Interval 3.0 to 15.0	7 Percentage of subjects Interval 2.0 to 14.0	—
Percentages of Subjects With hSBA Titers ≥ 1:5 Against N.Meningitidis Serogroup B Strains 44/76 and 5/99 44/76- 1 month after second dose	100 Percentage of subjects Interval 96.0 to 100.0	99 Percentage of subjects Interval 94.0 to 100.0	98 Percentage of subjects Interval 92.0 to 100.0	—
Percentages of Subjects With hSBA Titers ≥ 1:5 Against N.Meningitidis Serogroup B Strains 44/76 and 5/99 5/99- Baseline	11 Percentage of subjects Interval 6.0 to 20.0	15 Percentage of subjects Interval 8.0 to 25.0	16 Percentage of subjects Interval 9.0 to 25.0	—
Percentages of Subjects With hSBA Titers ≥ 1:5 Against N.Meningitidis Serogroup B Strains 44/76 and 5/99 5/99- 1 month after second dose	99 Percentage of subjects Interval 94.0 to 100.0	99 Percentage of subjects Interval 94.0 to 100.0	98 Percentage of subjects Interval 92.0 to 100.0	—

Adverse Events

ABCWY+OMV

Serious events: 2 serious events

Other events: 104 other events

Deaths: 0 deaths

ABCWY+qOMV

Serious events: 2 serious events

Other events: 104 other events

Deaths: 0 deaths

rMenB +OMV

Serious events: 1 serious events

Other events: 111 other events

Deaths: 0 deaths

ACWY

Serious events: 3 serious events

Other events: 87 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ABCWY+OMV n=120 participants at risk Subjects in this group received two doses of rMenB(+ OMV\_full dose) and MenACWY combination vaccine, administered two months apart.	ABCWY+qOMV n=120 participants at risk Subjects in this group received two doses of rMenB (+ OMV\_1/4th dose) +and MenACWY combination vaccine, administered two months apart.	rMenB +OMV n=120 participants at risk Subjects in this group received two doses of rMenB + OMV vaccine, administered two months apart.	ACWY n=109 participants at risk Subjects in this group received first dose of placebo followed by one dose of MenACWY vaccine administered two months apart.
Gastrointestinal disorders ABDOMINAL PAIN	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.92% 1/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Infections and infestations GASTROENTERITIS	0.83% 1/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Infections and infestations PERTUSSIS	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.83% 1/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Infections and infestations PNEUMONIA	0.83% 1/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Infections and infestations URINARY TRACT INFECTION	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.83% 1/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Nervous system disorders CONVULSION	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.83% 1/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Psychiatric disorders ABNORMAL BEHAVIOUR	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.83% 1/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Reproductive system and breast disorders SPERMATOCELE	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.92% 1/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Respiratory, thoracic and mediastinal disorders SLEEP APNOEA SYNDROME	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.92% 1/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).

Other adverse events

Additional Information

Posting Director

Novartis Vaccines

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	ABCWY+OMV n=120 participants at risk Subjects in this group received two doses of rMenB(+ OMV\_full dose) and MenACWY combination vaccine, administered two months apart.	ABCWY+qOMV n=120 participants at risk Subjects in this group received two doses of rMenB (+ OMV\_1/4th dose) +and MenACWY combination vaccine, administered two months apart.	rMenB +OMV n=120 participants at risk Subjects in this group received two doses of rMenB + OMV vaccine, administered two months apart.	ACWY n=109 participants at risk Subjects in this group received first dose of placebo followed by one dose of MenACWY vaccine administered two months apart.
Gastrointestinal disorders Diarrhoea	3.3% 4/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	1.7% 2/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	1.7% 2/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	5.5% 6/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Gastrointestinal disorders Nausea	12.5% 15/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	20.8% 25/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	25.8% 31/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	8.3% 9/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
General disorders Chills	15.8% 19/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	18.3% 22/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	24.2% 29/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	11.0% 12/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
General disorders Fatigue	27.5% 33/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	39.2% 47/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	43.3% 52/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	29.4% 32/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
General disorders Injection site Erythema	49.2% 59/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	44.2% 53/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	60.0% 72/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	29.4% 32/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
General disorders Injection site Induration	39.2% 47/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	43.3% 52/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	38.3% 46/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	22.9% 25/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
General disorders Injection site Pain	83.3% 100/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	80.8% 97/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	89.2% 107/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	51.4% 56/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
General disorders Pyrexia	11.7% 14/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	6.7% 8/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	5.8% 7/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	6.4% 7/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Infections and infestations Nasopharyngitis	2.5% 3/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	6.7% 8/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	5.0% 6/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	4.6% 5/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Infections and infestations Otitis media acute	1.7% 2/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.00% 0/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	1.7% 2/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	5.5% 6/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Infections and infestations Pharyngitis	5.8% 7/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	6.7% 8/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	5.8% 7/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	4.6% 5/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Infections and infestations Pharyngitis streptococcal	3.3% 4/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	4.2% 5/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	0.83% 1/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	8.3% 9/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Infections and infestations Upper respiratory tract infection	4.2% 5/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	6.7% 8/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	9.2% 11/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	7.3% 8/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Metabolism and nutrition disorders Decreased appetite	14.2% 17/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	18.3% 22/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	20.0% 24/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	11.0% 12/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Musculoskeletal and connective tissue disorders Arthralgia	18.3% 22/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	20.0% 24/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	20.8% 25/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	7.3% 8/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Musculoskeletal and connective tissue disorders Myalgia	54.2% 65/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	55.8% 67/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	55.8% 67/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	35.8% 39/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Nervous system disorders Headache	31.7% 38/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	34.2% 41/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	44.2% 53/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	29.4% 32/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	4.2% 5/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	3.3% 4/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	2.5% 3/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	6.4% 7/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).
Skin and subcutaneous tissue disorders Rash	5.0% 6/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	7.5% 9/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	3.3% 4/120 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).	5.5% 6/109 • Solicited AEs were collected from Day 1to Day 7; unsolicited AEs and SAEs were collected throughout the study period (Day 1 to Day 241).