Combined Study - Phase 3b MenB Long Term Persistence in Adolescents

The GMRs of GMTs at Day 1 versus one month after the last dose of rMenB+OMV NZ vaccination in the parent study were calculated. Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76, 5/99,NZ98/254 and M10713.

Time frame: Group 3B: 1 month after the last vaccination in parent study and Day 1 (prior to booster dose)

Population: Analysis was performed on the Full analysis set (FAS) persistence. The FAS included all follow-on subjects (Group 3B) in the All Enrolled Set, and all naïve subjects (B\_0\_1) in the All Enrolled Set who provided evaluable immunogenicity result at day 1, for at least one indicator strain.

Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76,5/99, NZ98/254 a nd M10713.

Time frame: Group 3B: 1 month after the last rMenB+OMV NZ vaccination in parent study and Day 1(prior to booster dose); Group B_0_1: Day 1(prior to first dose)

Population: Analysis was performed on the Full analysis set (FAS) persistence. The FAS included all follow-on subjects (Group 3B) in the All Enrolled Set, and all naïve subjects (group B\_0\_1) in the All Enrolled Set who provided evaluable immunogenicity result at day 1, for at least one indicator strain.

A serious adverse event is any untoward medical occurrence that at any dose results in death or is life threatening or requires prolonged hospitalization, leads to Persistent or significant disability/incapacity.

Time frame: Group 3B: from Day 1 to Day 31 (study termination visit) and Group B_0_1: from Day 1 to Day 61 (study termination visit)

Population: Analysis was performed on the Overall safety set. The overall safety set included all screened subjects in the solicited and unsolicited safety set who provided informed consent and provided demographic and/or baseline screening assessments, regardless of the subject's randomization and treatment status in the study and received a Subject ID.

An unsolicited adverse event is an adverse event that was not solicited using a subject Diary and that was spontaneously communicated by a subject and/or parent(s)/legal guardian(s) who has signed the informed consent. Note : Vaccination 2 was performed only on group B\_0\_1 subjects.

Time frame: 30 days (including the day of vaccination) after each vaccination.

Population: Analysis was performed on the unsolicited safety set. The unsolicited safety set included all subjects who received a study vaccination with unsolicited adverse event data.

Solicited adverse events are signs and symptoms derived from organized data collection systems, such as Subject Diaries or interview. The percentage and frequencies of subjects reporting solicited local and systemic AEs were tabulated. Threshold for any Erythema, Swelling and Induration: \>= 25 mm Note:Vaccination 2 was performed only on group B\_0\_1 subjects. Threshold for any Erythema, Swelling and Induration: \>= 25 mm

Time frame: 7 days (including the day of vaccination) after each vaccination

Population: The analysis was done on the Solicited Safety Set. The solicited safety set included all subjects in the exposed set with any solicited adverse event data and/indicators of solicited adverse events.

Bactericidal activity was measured against each of the N. meningitidis group B Indicator strains H44/76,5/99,NZ98/254 and M10713

Time frame: Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).

Population: Analysis was performed on the Full analysis set (FAS) persistence. The FAS included all follow-on subjects (Group 3B) in the All Enrolled Set, and all naïve subjects in the All Enrolled Set who provided evaluable immunogenicity result at day 1, for at least one indicator strain.

Bactericidal activity was measured against the N. meningitidis group B indicator strains H44/76 and M10713. This outcome measure was assessed only for strains H44/76 and M10713.

Time frame: Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).

Population: Analysis was performed on the Full analysis set (FAS) persistence.The FAS included all follow-on subjects (Group 3B) in the All Enrolled Set, and all naïve subjects (group B\_0\_1) in the All Enrolled Set who provided evaluable immunogenicity result at day 1, for at least one indicator strain.

Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713

Time frame: Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).

Population: Analysis was performed on the Full analysis set (FAS) persistence. The FAS included all follow-on subjects (Group 3B) in the All Enrolled Set, and all naïve subjects (group B\_0\_1) in the All Enrolled Set who provided evaluable immunogenicity result at day 1, for at least one indicator strain.

Bactericidal activity was measured against the N. meningitidis group B indicator strains H44/76 and M10713

Time frame: At one month after last vaccination in parent studies- V72P10 (Month 7) and V72_41 (Month 2)

Population: Analysis was performed on the Full analysis set (FAS) persistence. The FAS included all follow-on subjects (Group 3B) in the All Enrolled Set, and all naïve subjects (group B\_0\_1) in the All Enrolled Set who provided evaluable immunogenicity result at day 1, for at least one indicator strain.

Bactericidal activity was measured against the N. meningitidis group B indicator strains 5/99 and NZ98/254. This outcome measure was assessed only for strains 5/99 and NZ98/254.

Time frame: Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).

Population: Analysis was performed on the Full analysis set (FAS) persistence. The FAS included all follow-on subjects (Group 3B) in the All Enrolled Set,\& all naïve subjects (group B\_0\_1) in the All Enrolled Set who provided evaluable immunogenicity result at day 1,for at least one indicator strain.

Bactericidal activity was measured against each of the fout N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713 by calculating the GMRs of GMTs one month post-vaccination of a booster dose versus pre-booster dose (follow-on subjects) or first dose of rMenB+OMV NZ versus prefirst dose (naïve subjects) to each N. meningitidis group B indicator strain.

Time frame: At Day 31 (30 days post booster dose/first dose of vaccination) versus Day 1 (prior to booster dose/first dose of vaccination).

Population: Analysis was performed on the Full Analysis set( FAS) booster. The FAS booster included all follow on subjects and all naive subjects in the All enrolled set who received vaccination at day 1 and provided evaluable immunogenicity result at day 31 for at least one indicator strain.

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. Only subjects receiving a second vaccination (group B\_0\_1) were assessed for this outcome measure.

Time frame: At Day 1 & Day 61 (30 days post 2nd vaccination)

Population: Analysis was performed on the PPS( per protocol set) catch up. The PPS catch up included all subjects who were randomized to group B\_0\_1 who correctly received two vaccinations at day 1 and day 31 \& provided evaluable immunogenicity result at day 61 for atleast one indicator strain.

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713 by calculating the GMRs of GMTs post-vaccination with a booster dose (Group 3B) versus pre-booster dose or second dose (Group B\_0\_1) of vaccination versus pre second dose.

Time frame: Group 3B: Day 1 and 30 days after third dose booster; Group B_0_1: 30 days post-first dose and at 30 days post-second dose

Population: Analysis was performed on PPS kinetics which included all subjects who had no protocol deviations/any other reason defined prior to analysis, leading to exclusion \& correctly received the vaccination at day 1/day 31 \& day 1 \& provided evaluable immunogenicity result at all of days 4, 8 \& 31 (follow-on subjects)or at all of days 34, 38 \& 61(naive)

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. Only subjects receiving a second vaccination (group B\_0\_1) were assessed for this outcome measure.

Time frame: At Day 1 & Day 61 (30 days post second dose of vaccination)

Population: Analysis was performed on the PPS( per protocol set) catch up. The PPS catch up included all subjects who were randomized to group B\_0\_1 who correctly received two vaccinations at day 1 and day 31 \& provided evaluable immunogenicity result at day 61 for atleast one indicator strain.

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99,NZ98/254 and M10713.

Time frame: Group 3B subjects: Day 1(pre-booster dose) and 30 days post-booster dose. Group B_0_1: Day 1 (pre-first dose) and 30 days post-first dose.

Population: Analysis was performed on the Full Analysis set( FAS) booster. The FAS booster included all follow on subjects and all naive subjects in the All enrolled set who received vaccination at day 1 and provided evaluable immunogenicity result at day 31 for at least one indicator strain.

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. On day 1, subjects in the Group B\_0\_1 were to be randomized into 2 different blood draw schedules according to a 1:1 ratio : 2 blood samples at different time points: Group B\_0\_1\_1: blood draws at 3 and 30 days after the second dose. Group B\_0\_1\_2: blood draws at 7 and 30 days after the second dose.

Time frame: Group 3B: Day 1 (pre-booster dose) and 3, 7 and 30 days after third dose booster; Group B_0_1: Pre 2nd dose and at 3 (group B_0_1_1 only), 7 (group B_0_1_2 only) and 30 days post second dose.

Population: Analysis was performed on PPS kinetics which included all subjects who had no protocol deviations/any other reason defined prior to analysis, leading to exclusion \& correctly received the vaccination at day 1/day 31 \& day 1 \& provided evaluable immunogenicity result at all of days 4, 8 \& 31 (follow-on subjects)or at all of days 34, 38 \& 61(naive)

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 & M10713.

Time frame: Group 3B: 30 days after booster dose, Group B_0_1 : 30 days after first vaccination.

Population: Analysis was performed on the Full Analysis set( FAS) booster. The FAS booster included all follow on subjects and all naive subjects in the All enrolled set who received vaccination at day 1 and provided evaluable immunogenicity result at day 31 for at least one indicator strain.

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. On day 1, subjects in the Group B\_0\_1 were to be randomized into 2 different blood draw schedules according to a 1:1 ratio : 2 blood samples at different time points: Group B\_0\_1\_1: blood draws at 3 and 30 days after the second dose. Group B\_0\_1\_2: blood draws at 7 and 30 days after the second dose

Time frame: Group 3B: 3, 7 and 30 days after third dose booster; Group B_0_1: At 3 (group B_0_1_1 only), 7 (sub-group B_0_1_2 only) and 30 days post-second dose

Population: Analysis was performed on PPS kinetics which included all subjects who had no protocol deviations/any other reason defined prior to analysis, leading to exclusion \& correctly received the vaccination at day 1/day 31 \& day 1 \& provided evaluable immunogenicity result at all of days 4, 8 \& 31 (follow-on subjects)or at all of days 34, 38 \& 61(naive)

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. Only subjects receiving a second vaccination (group B\_0\_1) were assessed for this outcome measure.

Time frame: At Day 61 (30 days post second vaccination)

Population: Analysis was performed on the PPS( per protocol set) catch up. The PPS catch up included all subjects who were randomized to group B\_0\_1 who correctly received two vaccinations at day 1 and day 31 \& provided evaluable immunogenicity result at day 61 for atleast one indicator strain.

Bactericidal activity was measured against the N. meningitidis group B indicator strains 5/99 and NZ98/254. This outcome measure was assessed only for strains 5/99 and NZ98/254.

Time frame: Group 3B: 30 days after booster dose, Group B_0_1 : 30 days after first vaccination.

Population: Analysis was performed on the Full Analysis set( FAS) booster. The FAS booster included all follow on subjects and all naive subjects in the All enrolled set who received vaccination at day 1 and provided evaluable immunogenicity result at day 31 for at least one indicator strain.

Bactericidal activity was measured against the N. meningitidis group B indicator strains 5/99 and NZ98/254. On day 1, subjects in the Group B\_0\_1 were to be randomized into 2 different blood draw schedules according to a 1:1 ratio : 2 blood samples at different time points: Group B\_0\_1\_1: blood draws at 3 and 30 days after the second dose. Group B\_0\_1\_2: blood draws at 7 and 30 days after the second dose. This outcome measure was assessed only for strains 5/99 and NZ98/254.

Time frame: Group 3B: 3, 7 and 30 days after third dose booster; Group B_0_1: At 3 (group B_0_1_1 only), 7 (sub-group B_0_1_2 only) and 30 days post-second dose.

Population: Analysis was performed on PPS kinetics which included all subjects who correctly received the vaccination at day 1/ day 1 \& day 31 (naive subjects) \& provided evaluable immunogenicity result at all of days 4, 8 \& 31 (for follow-on subjects) or at all of days 34,38 and 61 (naive subjects).

Bactericidal activity was measured against the N. meningitidis group B indicator strains 5/99 and NZ98/254. Only subjects receiving a second vaccination (group B\_0\_1) were assessed for this outcome measure.

Time frame: At Day 61 (30 days post second dose of vaccination.)

Population: Analysis was performed on the PPS( per protocol set) catch up. The PPS catch up included all subjects who were randomized to group B\_0\_1 who correctly received two vaccinations at day 1 and day 31 \& provided evaluable immunogenicity result at day 61 for atleast one indicator strain. The analysis was performed only on strains 5/99 and NZ98/254

Bactericidal activity was measured against the N. meningitidis group B indicator strains H44/76 and M10713. This outcome measure was assessed only for strains H44/76 and M10713.

Time frame: Group 3B: 30 days after booster dose, Group B_0_1 : 30 days after first vaccination.

Population: Analysis was performed on the Full Analysis set( FAS) booster. The FAS booster included all follow on subjects and all naive subjects in the All enrolled set who received vaccination at day 1 and provided evaluable immunogenicity result at day 31 for at least one indicator strain.

Bactericidal activity was measured against the N. meningitidis group B indicator strains H44/76 and M10713. On day 1, subjects in the Group B\_0\_1 were to be randomized into 2 different blood draw schedules according to a 1:1 ratio : 2 blood samples at different time points: Group B\_0\_1\_1: blood draws at 3 and 30 days after the second dose. Group B\_0\_1\_2: blood draws at 7 and 30 days after the second dose. This outcome measure was assessed only for strains H44/76 and M10713.

Time frame: Group 3B: 3, 7 and 30 days after third dose booster; Group B_0_1: At 3 (group B_0_1_1 only), 7 (sub-group B_0_1_2 only) and 30 days post-second dose.

Population: Analysis was performed on the PPS kinetics which included all subjects who correctly received the vaccination at day 1/ day 1 \& day 31 (naive subjects) \& provided evaluable immunogenicity result at all of days 4, 8 \& 31 (for follow-on subjects) or at all of days 34,38 \& 61 (naive subjects).

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76 and M10713. Only subjects receiving a second vaccination (group B\_0\_1) were assessed for this outcome measure.

Time frame: At Day 61 (30 days post second dose of vaccination.)

Population: Analysis was performed on the PPS( per protocol set) catch up. The PPS catch up included all subjects who were randomized to group B\_0\_1 who correctly received two vaccinations at day 1 and day 31 \& provided evaluable immunogenicity result at day 61 for atleast one indicator strain. The analysis was performed only on strains H44/76 and M10713

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713.

Time frame: Group 3B : 30 days after booster dose, Group B_0_1 : 30 days after first vaccination.

Population: Analysis was performed on the Full Analysis set( FAS) booster. The FAS booster included all follow on subjects and all naive subjects in the All enrolled set who received vaccination at day 1 and provided evaluable immunogenicity result at day 31 for at least one indicator strain.

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. On day 1, subjects in the Group B\_0\_1 were to be randomized into 2 different blood draw schedules according to a 1:1 ratio : 2 blood samples at different time points: Group B\_0\_1\_1: blood draws at 3 and 30 days after the second dose. Group B\_0\_1\_2: blood draws at 7 and 30 days after the second dose.

Time frame: Group 3B: 3, 7 and 30 days after third dose booster; Group B_0_1: At 3 (group B_0_1_1 only), 7 (sub-group B_0_1_2 only) and 30 days post-second dose.

Population: Analysis was performed on PPS kinetics which included all subjects who had no protocol deviations/any other reason defined prior to analysis, leading to exclusion \& correctly received the vaccination at day 1/day 31 \& day 1 \& provided evaluable immunogenicity result at all of days 4, 8 \& 31 (follow-on subjects)or at all of days 34, 38 \& 61(naive)

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. Only subjects receiving a second vaccination (group B\_0\_1) were assessed for this outcome measure.

Time frame: At Day 61 (30 days post second vaccination)

Population: Analysis was performed on the PPS( per protocol set) catch up. The PPS catch up included all subjects who were randomized to group B\_0\_1 who correctly received two vaccinations at day 1 and day 31 \& provided evaluable immunogenicity result at day 61 for atleast one indicator strain.

The percentage of subjects with 4-fold rise at one month post-vaccination with a booster dose (follow-on subjects) /first dose (naive subjects) of rMenB+OMV NZ with respect to day 1 (follow-on subjects) / pre-first dose of rMenB+OMV NZ (naïve subjects). Percentage of subjects with four-fold rise in hSBA titers relative to baseline were defined as: • for a pre-vaccination titer \< 4, a post-vaccination titer of at least 16; • for a pre-vaccination titer ≥ 4 but \<LLOQ, a post vaccination titer of at least fourfold the LLOQ; • for a pre-vaccination titer ≥LLOQ, a post vaccination titer of at least fourfold the pre-vaccination titer

Time frame: Group 3B: 1 month after booster dose; Group B_0_1: 1 month after first vaccination

Population: Analysis was performed on the Full Analysis set (FAS) booster. The FAS booster included all follow on subjects and all naive subjects in the All enrolled set who received vaccination at day 1 and provided evaluable immunogenicity result at day 31 for atleast one indicator strain.

The percentage of subjects with 4-fold rise at one month post-vaccination with a second dose (naïve subjects) of rMenB+OMV NZ with respect to day 1, to each and any one, two, three or all 4 indicator strains. Percentage of subjects with four-fold rise in hSBA titers relative to baseline were defined as: * for a pre-vaccination titer \< 4, a post-vaccination titer of at least 16; * for a pre-vaccination titer ≥ 4 but \<LLOQ, a post vaccination titer of at least fourfold the LLOQ; * for a pre-vaccination titer ≥LLOQ, a post vaccination titer of at least fourfold the pre-vaccination titer. Only subjects receiving the second dose of vaccination(group B\_0\_1) were considered for this outcome measure.

Time frame: At Day 61 (30 days post second dose of vaccination)

Population: Analysis was performed on the PPS( per protocol set) catch up. The PPS catch up included all subjects who were randomized to group B\_0\_1 who correctly received two vaccinations at day 1 and day 31 \& provided evaluable immunogenicity result at day 61 for atleast one indicator strain.

The percentage of subjects with 4-fold rise at 3, 7, 30 days post-vaccination with a booster dose (follow-on subjects) /second dose (naive subjects) of rMenB+OMV NZ with respect to day 1 (follow-on subjects) / pre-second dose of rMenB+OMV NZ (naïve subjects). Percentage of subjects with four-fold rise in hSBA titers relative to baseline were defined as: • for a pre-vaccination titer \< 4, a post-vaccination titer of at least 16; • for a pre-vaccination titer ≥ 4 but \<LLOQ, a post vaccination titer of at least fourfold the LLOQ; • for a pre-vaccination titer ≥LLOQ, a post vaccination titer of at least fourfold the pre-vaccination titer.

Time frame: Group 3B: at 3, 7 and 30 days after third dose booster; Group B_0_1: at 3 (group B_0_1_1 only), 7 (group B_0_1_2 only) and 30 days post second dose

Population: Analysis was performed on PPS kinetics which included all subjects who had no protocol deviations/any other reason defined prior to analysis, leading to exclusion \& correctly received the vaccination at day 1/day 31 \& day 1 \& provided evaluable immunogenicity result at all of days 4, 8 \& 31 (follow-on subjects)or at all of days 34/38 \& 61(naive)