Trial Outcomes & Findings for Safety and Immunogenicity of Novartis Meningococcal B Vaccine Formulated With OMV Manufactured at Two Different Sites, in Healthy Adolescents Aged 11-17 Years (NCT NCT01423084)
NCT ID: NCT01423084
Last Updated: 2015-02-20
Results Overview
Consistency of the immune response of the two lots of rMenB+OMV NZ will be assessed at one month after the second vaccination based on the ratio of the vaccine lot hSBA GMTs for each of three serogroup B reference strains (H44/76, 5/99, and NZ98/254) and based on the ratio of Enzyme-linked Immunosorbent Assay (ELISA) GMCs for vaccine antigen 287-953. The equivalence interval will be (0.5, 2.0).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
344 participants
Primary outcome timeframe
One month after the second vaccination (day 61)
Results posted on
2015-02-20
Participant Flow
Actual start date of recruiting was 30 August 2011. Subjects were recruited from 7 centres in Canada and 6 centres in Australia.
All subjects were enrolled in the trial.
Participant milestones
| Measure |
4CMenB_Rosia
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
Overall Study
STARTED
|
170
|
174
|
|
Overall Study
COMPLETED
|
168
|
170
|
|
Overall Study
NOT COMPLETED
|
2
|
4
|
Reasons for withdrawal
| Measure |
4CMenB_Rosia
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
3
|
Baseline Characteristics
Safety and Immunogenicity of Novartis Meningococcal B Vaccine Formulated With OMV Manufactured at Two Different Sites, in Healthy Adolescents Aged 11-17 Years
Baseline characteristics by cohort
| Measure |
4CMenB_Rosia
n=170 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=174 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
Total
n=344 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
13.6 years
STANDARD_DEVIATION 1.9 • n=5 Participants
|
13.8 years
STANDARD_DEVIATION 1.8 • n=7 Participants
|
13.7 years
STANDARD_DEVIATION 1.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
72 Participants
n=5 Participants
|
82 Participants
n=7 Participants
|
154 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
98 Participants
n=5 Participants
|
92 Participants
n=7 Participants
|
190 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: One month after the second vaccination (day 61)Population: Per Protocol Set population
Consistency of the immune response of the two lots of rMenB+OMV NZ will be assessed at one month after the second vaccination based on the ratio of the vaccine lot hSBA GMTs for each of three serogroup B reference strains (H44/76, 5/99, and NZ98/254) and based on the ratio of Enzyme-linked Immunosorbent Assay (ELISA) GMCs for vaccine antigen 287-953. The equivalence interval will be (0.5, 2.0).
Outcome measures
| Measure |
4CMenB_Rosia
n=147 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=151 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) Against 3 Neisseria.Meningitidis (N. Meningitidis) Serogroup B Reference Strains.
H44/76 strain
|
111 Titers
Interval 96.0 to 129.0
|
111 Titers
Interval 96.0 to 128.0
|
|
Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) Against 3 Neisseria.Meningitidis (N. Meningitidis) Serogroup B Reference Strains.
NZ98/254 strain
|
9.27 Titers
Interval 7.44 to 12.0
|
11 Titers
Interval 9.22 to 14.0
|
|
Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) Against 3 Neisseria.Meningitidis (N. Meningitidis) Serogroup B Reference Strains.
5/99 strain (N=152)
|
183 Titers
Interval 160.0 to 209.0
|
199 Titers
Interval 174.0 to 227.0
|
PRIMARY outcome
Timeframe: One month after the second vaccination (day 61)Population: Per Protocol Set population
The immune response of two different lots of rMenB+OMV NZ is evaluated in terms of ELISA GMCs against vaccine antigen 287-953.
Outcome measures
| Measure |
4CMenB_Rosia
n=147 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=152 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
ELISA Geometric Mean Concentration (GMCs) Against Vaccine Antigen 287-953
|
2729 IU/ml
Interval 2338.0 to 3186.0
|
3291 IU/ml
Interval 2829.0 to 3828.0
|
SECONDARY outcome
Timeframe: One month after the second vaccination (day 61)Population: Per Protocol Set population
The percentage of subjects in each lot with hSBA ≥ 1:5 at one month after the second vaccination for each of the three reference strains (H44/76, 5/99, and NZ98/254) for each vaccine group
Outcome measures
| Measure |
4CMenB_Rosia
n=147 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=152 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
Percentage of Subjects in Each Lot With hSBA ≥ 1:5
H44/76 strain (N=151)
|
99 Percentage of subjects
Interval 96.0 to 100.0
|
99 Percentage of subjects
Interval 96.0 to 100.0
|
|
Percentage of Subjects in Each Lot With hSBA ≥ 1:5
NZ98/254 strain (N=151)
|
70 Percentage of subjects
Interval 62.0 to 77.0
|
79 Percentage of subjects
Interval 72.0 to 86.0
|
|
Percentage of Subjects in Each Lot With hSBA ≥ 1:5
5/99 strain
|
100 Percentage of subjects
Interval 98.0 to 100.0
|
100 Percentage of subjects
Interval 98.0 to 100.0
|
SECONDARY outcome
Timeframe: One month after the second vaccination (day 61)Population: Per Protocol Set Population
The immune response of two different lots of rMenB+OMV NZ against each of N. meningitidis serogroup B test strains is evaluated in terms of GMR between GMTs (1month after the second vaccination vs baseline).
Outcome measures
| Measure |
4CMenB_Rosia
n=147 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=152 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
Geometric Mean Ratio (GMR) of GMTs Against Each of N. Meningitidis Serogroup B Reference Strains.
H44/76 strain (N=151)
|
104 Ratio of GMTs
Interval 89.0 to 121.0
|
107 Ratio of GMTs
Interval 92.0 to 124.0
|
|
Geometric Mean Ratio (GMR) of GMTs Against Each of N. Meningitidis Serogroup B Reference Strains.
NZ98/254 strain (N=151)
|
8.63 Ratio of GMTs
Interval 6.99 to 11.0
|
11 Ratio of GMTs
Interval 8.99 to 14.0
|
|
Geometric Mean Ratio (GMR) of GMTs Against Each of N. Meningitidis Serogroup B Reference Strains.
5/99
|
156 Ratio of GMTs
Interval 133.0 to 183.0
|
167 Ratio of GMTs
Interval 143.0 to 195.0
|
SECONDARY outcome
Timeframe: One month after the second vaccination (day 61)Population: Per Protocol Set Population
The immune response of two different lots of rMenB+OMV NZ against antigen 287-953 is evaluated in terms of GMRs between ELISA GMCs (day 61 vs baseline).
Outcome measures
| Measure |
4CMenB_Rosia
n=145 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=152 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
Geometric Mean Ratio (GMR) of ELISA Geometric Mean Concentration (GMCs) Against Antigen 287-953
|
122 Ratio of GMTs
Interval 103.0 to 143.0
|
153 Ratio of GMTs
Interval 131.0 to 179.0
|
SECONDARY outcome
Timeframe: Two weeks after the second vaccination (day 45)Population: Per Protocol Set, immunogenicity subset
The immunogenicity of two different lots of rMenB+OMV NZ is evaluated in terms of hSBA GMT against 3 N. Meningitidis serogroup B reference strains at two weeks after last vaccination.
Outcome measures
| Measure |
4CMenB_Rosia
n=76 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=71 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
hSBA GMT Against 3 N. Meningitidis Serogroup B Reference Strains at Day 45.
H44/76 strain
|
187 Titers
Interval 152.0 to 229.0
|
171 Titers
Interval 139.0 to 210.0
|
|
hSBA GMT Against 3 N. Meningitidis Serogroup B Reference Strains at Day 45.
NZ98/254 strain
|
14 Titers
Interval 10.0 to 18.0
|
20 Titers
Interval 15.0 to 27.0
|
|
hSBA GMT Against 3 N. Meningitidis Serogroup B Reference Strains at Day 45.
5/99 strain
|
254 Titers
Interval 206.0 to 314.0
|
339 Titers
Interval 273.0 to 420.0
|
SECONDARY outcome
Timeframe: Two weeks after the second vaccination (day 45)Population: Per Protocol Set, Immunogenicity subset
The immunogenicity of two different lots of rMenB+OMV NZ is evaluated in terms of GMRs of GMT against 3 N. meningitidis serogroup B reference strains at two weeks after last vaccination.
Outcome measures
| Measure |
4CMenB_Rosia
n=76 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=71 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
GMRs of GMT Against 3 N. Meningitidis Serogroup B Reference Strains at Day 45.
H44/76 strain
|
174 Ratio of GMTs
Interval 138.0 to 219.0
|
157 Ratio of GMTs
Interval 124.0 to 199.0
|
|
GMRs of GMT Against 3 N. Meningitidis Serogroup B Reference Strains at Day 45.
NZ98/254
|
13 Ratio of GMTs
Interval 9.87 to 17.0
|
20 Ratio of GMTs
Interval 15.0 to 26.0
|
|
GMRs of GMT Against 3 N. Meningitidis Serogroup B Reference Strains at Day 45.
5/99 strain
|
214 Ratio of GMTs
Interval 161.0 to 284.0
|
243 Ratio of GMTs
Interval 183.0 to 325.0
|
SECONDARY outcome
Timeframe: Two weeks after the second vaccination (day 45)Population: Per Protocol Population, immunogenicity subset
The immune response of two different lots of rMenB+OMV NZ against each of N. Meningitidis serogroup B reference strains is evaluated in terms of percentages of subjects with hSBA ≥1:5 two weeks after the last vaccination.
Outcome measures
| Measure |
4CMenB_Rosia
n=76 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=71 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
Percentage of Subjects With hSBA ≥1:5 Against Each of N. Meningitidis Serogroup B Reference Strains at Day 45.
H44/76 strain
|
100 Percentage of subjects
Interval 95.0 to 100.0
|
100 Percentage of subjects
Interval 95.0 to 100.0
|
|
Percentage of Subjects With hSBA ≥1:5 Against Each of N. Meningitidis Serogroup B Reference Strains at Day 45.
NZ98/254 strain
|
84 Percentage of subjects
Interval 74.0 to 92.0
|
96 Percentage of subjects
Interval 88.0 to 99.0
|
|
Percentage of Subjects With hSBA ≥1:5 Against Each of N. Meningitidis Serogroup B Reference Strains at Day 45.
5/99 strain
|
100 Percentage of subjects
Interval 95.0 to 100.0
|
100 Percentage of subjects
Interval 95.0 to 100.0
|
SECONDARY outcome
Timeframe: Two weeks after the second vaccination (day 45)Population: Per Protocol Set, immunogenicity subset.
The immune response of two different lots of rMenB+OMV NZ is evaluated in terms of ELISA GMCs against vaccine antigen 287-953.
Outcome measures
| Measure |
4CMenB_Rosia
n=76 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=71 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
ELISA GMCs Against Vaccine Antigen 287-953 at Day 45.
|
3742 IU/ml
Interval 2994.0 to 4676.0
|
4798 IU/ml
Interval 3825.0 to 6019.0
|
SECONDARY outcome
Timeframe: Two weeks after the second vaccination (day 45)Population: Per Protocol Set, immunogenicity subset
The immune response of two different lots of rMenB+OMV NZ against antigen 287-953 is evaluated in terms of GMRs between ELISA GMCs (day 45 vs baseline).
Outcome measures
| Measure |
4CMenB_Rosia
n=74 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=71 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
GMR of ELISA GMCs Against Antigen 287-953 at Day 45.
|
166 Ratio of GMTs
Interval 130.0 to 213.0
|
217 Ratio of GMTs
Interval 169.0 to 279.0
|
SECONDARY outcome
Timeframe: From day 1 to day 7 after any vaccinationPopulation: Safety Set
Number of subjects reporting solicited local and systemic Adverse Events and other indicators of reactogenicity after any vaccination.
Outcome measures
| Measure |
4CMenB_Rosia
n=169 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=173 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Any local
|
163 Number of subjects
|
170 Number of subjects
|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Induration
|
65 Number of subjects
|
75 Number of subjects
|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Pain
|
162 Number of subjects
|
170 Number of subjects
|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Erythema
|
111 Number of subjects
|
111 Number of subjects
|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Swelling
|
80 Number of subjects
|
74 Number of subjects
|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Any systemic
|
136 Number of subjects
|
150 Number of subjects
|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Nausea
|
49 Number of subjects
|
56 Number of subjects
|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Fatigue
|
75 Number of subjects
|
85 Number of subjects
|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Myalgia
|
99 Number of subjects
|
118 Number of subjects
|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Arthralgia
|
28 Number of subjects
|
44 Number of subjects
|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Headache
|
75 Number of subjects
|
89 Number of subjects
|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Fever (>= 38C)
|
8 Number of subjects
|
5 Number of subjects
|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Rash
|
11 Number of subjects
|
16 Number of subjects
|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Any other
|
87 Number of subjects
|
96 Number of subjects
|
|
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Use of analgesics
|
82 Number of subjects
|
92 Number of subjects
|
SECONDARY outcome
Timeframe: From day 1 to day 7 after any vaccination.Population: Safety Set
Number of subjects reporting any Unsolicited AEs after any vaccination.
Outcome measures
| Measure |
4CMenB_Rosia
n=169 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=173 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
Number of Subjects Reporting Unsolicited AEs
|
56 Number of subjects
|
55 Number of subjects
|
SECONDARY outcome
Timeframe: Throughout the study period.Population: Safety Set
Number of subjects reporting any Serious AEs (SAEs), medically attended AEs and AEs that result in a subject's withdrawal from the study after any vaccination.
Outcome measures
| Measure |
4CMenB_Rosia
n=169 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=173 Participants
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
Number of Subjects Reporting SAEs and AE Leading to Withdrawal
Serious Adverse Events
|
0 Number of subjects
|
0 Number of subjects
|
|
Number of Subjects Reporting SAEs and AE Leading to Withdrawal
Adverse Events
|
0 Number of subjects
|
1 Number of subjects
|
Adverse Events
4CMenB_Rosia
Serious events: 0 serious events
Other events: 165 other events
Deaths: 0 deaths
4CMenB_Siena
Serious events: 0 serious events
Other events: 171 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
4CMenB_Rosia
n=169 participants at risk
Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
|
4CMenB_Siena
n=173 participants at risk
Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
|
|---|---|---|
|
Investigations
injection site swelling
|
47.3%
80/169 • Number of events 115 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
42.8%
74/173 • Number of events 107 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
|
Nervous system disorders
Headache
|
44.4%
75/169 • Number of events 124 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
51.4%
89/173 • Number of events 159 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
|
General disorders
Fatigue
|
44.4%
75/169 • Number of events 129 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
49.1%
85/173 • Number of events 138 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
|
General disorders
injection site induration
|
38.5%
65/169 • Number of events 96 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
43.4%
75/173 • Number of events 107 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
|
General disorders
injection site erythema
|
65.7%
111/169 • Number of events 177 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
64.2%
111/173 • Number of events 175 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
|
General disorders
injection site pain
|
95.9%
162/169 • Number of events 337 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
98.3%
170/173 • Number of events 349 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
|
Gastrointestinal disorders
nausea
|
29.0%
49/169 • Number of events 68 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
32.4%
56/173 • Number of events 77 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
|
Skin and subcutaneous tissue disorders
rash
|
6.5%
11/169 • Number of events 13 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
9.2%
16/173 • Number of events 18 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
16.6%
28/169 • Number of events 38 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
26.0%
45/173 • Number of events 66 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
|
Musculoskeletal and connective tissue disorders
myalgia
|
58.6%
99/169 • Number of events 169 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
68.2%
118/173 • Number of events 189 • SAEs were collected from day 1 through study termination, other AEs were collected from day 1 to day 7 after vaccination.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60