Safety and Immunogenicity of Novartis Meningococcal B Vac... | NCT02141516

NCT02141516

ID	Type	Description	Link
2013-002454-78	EudraCT Number

Status Module

Sponsor/Collaborators Module

Name	Class
Novartis Vaccines	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Group A	Experimental	Complement deficiency	Biological: rMenB+OMV
Group B	Experimental	asplenia/splenic dysfunction	Biological: rMenB+OMV
Group C	Active Comparator	age-matched healthy controls	Biological: rMenB+OMV

Name	Type	Description	Arm Group Labels	Other Names
rMenB+OMV	Biological	2 doses of vaccine 2 months apart	Group A

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentages of Subjects With Serum Bactericidal Activity Using Human Complement (hSBA) Titers ≥ 5 for B Indicator Strains (H44/76, 5/99, and NZ98/254) and M10713 Strain.	Immunogenicity was assessed in terms of percentage of subjects with hSBA titers ≥ 5 against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+Outer Membrane Vesicle (OMV) NZ, administered on Day 1 and Day 61.	Day 1 and Day 91 (one month after the second dose of the study vaccine)
Percentages of Subjects With hSBA Titers ≥ 8 for B Indicator Strains (H44/76, 5/99, and NZ98/254) and M10713 Strain.	Immunogenicity was assessed in terms of percentage of subjects with hSBA titers ≥ 8 against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.	Day 1 and Day 91 (one month after the second dose of the study vaccine).
Geometric Mean Ratios (GMRs) Against N. Meningitidis Serogroup B Strains Following a 2-dose Vaccination Schedule.	Immunogenicity was assessed in terms of GMRs against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.	Day 1 and Day 91 (one month after the second dose of the study vaccine).
Geometric Mean hSBA Titers (GMTs) Against N. Meningitidis Serogroup B Strains Following a 2-dose Vaccination Schedule.	Immunogenicity was assessed in terms of GMTs against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.	Day 1 and Day 91 (one month after the second dose of the study vaccine).
Percentages of Subjects With Four-fold Increases in hSBA Titers Against the Serogroup B Indicator Strains (H44/76, 5/99, and NZ98/254) and M10713 Strain.

Secondary Outcomes

Measure	Description	Time Frame
Number of Subjects Reporting Solicited Local and Systemic AEs.	Reactogenicity was presented in terms of percentages of subjects reporting solicited local and systemic AEs and other indicators.	From Day 1 until Day 7 after any vaccination.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Novartis Vaccines	Novartis Vaccines	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
12, Novartis Investigational Site		Florence		50139	Italy
11, Novartis Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
30068713	Derived	Martinon-Torres F, Bernatowska E, Shcherbina A, Esposito S, Szenborn L, Marti MC, Hughes S, Faust SN, Gonzalez-Granado LI, Yu LM, D'Agostino D, Calabresi M, Toneatto D, Snape MD. Meningococcal B Vaccine Immunogenicity in Children With Defects in Complement and Splenic Function. Pediatrics. 2018 Sep;142(3):e20174250. doi: 10.1542/peds.2017-4250. Epub 2018 Aug 1.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	CompDef	Subjects aged ≥ 2 to ≤ 17 years with complement deficiencies received 2 doses of rMenB+OMV NZ administered 2 months apart.
FG001	Asplenia	Subjects aged ≥ 2 to ≤ 17 years with Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	CompDef	Subjects aged ≥ 2 to ≤ 17 years with complement deficiencies received 2 doses of rMenB+OMV NZ administered 2 months apart.
BG001	Asplenia	Subjects aged ≥ 2 to ≤17 years with Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
BG002	Healthy	Healthy subjects aged ≥ 2 to ≤ 17 years received 2 doses of rMenB+OMV NZ administered 2 months apart.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

5/99 - Day 1 (N=37,103,140,82)

Title	Measurements
	OG0000(0 to 9.5) OG00112(6.2 to 19.5) OG0029(4.5 to 14.5) OG003

Primary

Percentages of Subjects With hSBA Titers ≥ 8 for B Indicator Strains (H44/76, 5/99, and NZ98/254) and M10713 Strain.

Immunogenicity was assessed in terms of percentage of subjects with hSBA titers ≥ 8 against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.

Analysis was done on Full Analysis Set

Posted

Number

95% Confidence Interval

Percentage of Subjects

Day 1 and Day 91 (one month after the second dose of the study vaccine).

ID	Title	Description
OG000	CompDef	Subjects aged ≥ 2 to ≤ 17 years with complement deficiencies received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG001	Asplenia	Subjects aged ≥ 2 to ≤ 17 years with Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG002	CompDef + Asplenia	Subjects aged ≥ 2 to ≤ 17 years with either complement deficiencies or Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG003	Healthy

Primary

Geometric Mean Ratios (GMRs) Against N. Meningitidis Serogroup B Strains Following a 2-dose Vaccination Schedule.

Immunogenicity was assessed in terms of GMRs against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.

Analysis was done on Full Analysis Set

Posted

Geometric Mean

95% Confidence Interval

Ratios

Day 1 and Day 91 (one month after the second dose of the study vaccine).

ID	Title	Description
OG000	CompDef	Subjects aged ≥ 2 to ≤ 17 years with complement deficiencies received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG001	Asplenia	Subjects aged ≥ 2 to ≤ 17 years with Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG002	CompDef + Asplenia	Subjects aged ≥ 2 to ≤ 17 years with either complement deficiencies or Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG003	Healthy

Primary

Geometric Mean hSBA Titers (GMTs) Against N. Meningitidis Serogroup B Strains Following a 2-dose Vaccination Schedule.

Immunogenicity was assessed in terms of GMTs against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.

Analysis was done on Full Analysis Set.

Posted

Geometric Mean

95% Confidence Interval

Titers

Day 1 and Day 91 (one month after the second dose of the study vaccine).

ID	Title	Description
OG000	CompDef	Subjects aged ≥ 2 to ≤ 17 years with complement deficiencies received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG001	Asplenia	Subjects aged ≥ 2 to ≤ 17 years with Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG002	CompDef + Asplenia	Subjects aged ≥ 2 to ≤ 17 years with either complement deficiencies or Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG003	Healthy

Primary

Percentages of Subjects With Four-fold Increases in hSBA Titers Against the Serogroup B Indicator Strains (H44/76, 5/99, and NZ98/254) and M10713 Strain.

Antibody responses were assessed in terms of percentage of subjects achieving 4-fold increase in ELISA concentrations against vaccine antigen 287-953 on Day 91 over baseline (Day 1), following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.

Analysis was done on Full Analysis Set

Posted

Number

95% Confidence Interval

Percentage of Subjects

Day 91 (one month after the second dose of the study vaccine).

ID	Title	Description
OG000	CompDef	Subjects aged ≥ 2 to ≤ 17 years with complement deficiencies received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG001	Asplenia	Subjects aged ≥ 2 to ≤ 17 years with Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG002	CompDef + Asplenia	Subjects aged ≥ 2 to ≤ 17 years with either complement deficiencies or Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG003	Healthy

Primary

Geometric Mean Concentrations (GMCs) of Antibodies Against Vaccine Antigen 287-953 Following a 2-dose Vaccination Schedule.

Immune responses were measured as Enzyme-linked Immunosorbent Assay (ELISA) GMCs of antibodies against vaccine antigen 287-953 following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.

Analysis was done on Full Analysis Set

Posted

Geometric Mean

95% Confidence Interval

IU/mL

Day 1 and Day 91 (one month after the second dose of the study vaccine).

ID	Title	Description
OG000	CompDef	Subjects aged ≥ 2 to ≤ 17 years with complement deficiencies received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG001	Asplenia	Subjects aged ≥ 2 to ≤ 17 years with Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG002	CompDef + Asplenia	Subjects aged ≥ 2 to ≤ 17 years with either complement deficiencies or Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG003	Healthy

Primary

ELISA GMRs of Antibodies Against Vaccine Antigen 287-953 Following a 2-dose Vaccination Schedule.

Immune responses were measured as ELISA GMRs of antibodies against vaccine antigen 287-953 following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.

Analysis was done on Full Analysis Set

Posted

Geometric Mean

95% Confidence Interval

Ratios

Day 1 and Day 91 (one month after the second dose of the study vaccine).

ID	Title	Description
OG000	CompDef	Subjects aged ≥ 2 to ≤ 17 years with complement deficiencies received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG001	Asplenia	Subjects aged ≥ 2 to ≤ 17 years with Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG002	CompDef + Asplenia	Subjects aged ≥ 2 to ≤ 17 years with either complement deficiencies or Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG003	Healthy	Healthy subjects aged ≥ 2 to ≤ 17 years received 2 doses of rMenB+OMV NZ administered 2 months apart.

Primary

Percentage of Subjects With Four-fold Increases in ELISA Concentrations Against the Vaccine Antigen 287-953.

Analysis was done on Full Analysis Set

Posted

Number

95% Confidence Interval

Percentage of Subjects

Day 91 (one month after the second dose of the study vaccine).

ID	Title	Description
OG000	CompDef	Subjects aged ≥ 2 to ≤ 17 years with complement deficiencies received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG001	Asplenia	Subjects aged ≥ 2 to ≤ 17 years with Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG002	CompDef + Asplenia	Subjects aged ≥ 2 to ≤ 17 years with either complement deficiencies or Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG003	Healthy

Secondary

Number of Subjects Reporting Solicited Local and Systemic AEs.

Reactogenicity was presented in terms of percentages of subjects reporting solicited local and systemic AEs and other indicators.

Analysis was done on Solicited Safety Set (all subjects in the exposed set with any solicited AE data).

Posted

Number

participants

From Day 1 until Day 7 after any vaccination.

ID	Title	Description
OG000	CompDef	Subjects aged ≥ 2 to ≤ 17 years with complement deficiencies received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG001	Asplenia	Subjects aged ≥ 2 to ≤ 17 years with Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG002	CompDef + Asplenia	Subjects aged ≥ 2 to ≤ 17 years with either complement deficiencies or Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG003	Healthy	Healthy subjects aged ≥ 2 to ≤ 17 years received 2 doses of rMenB+OMV NZ administered 2 months apart.

Primary

Number Of Subjects With Unsolicited Adverse Events (AEs).

Safety was assessed as the number of subjects who reported unsolicited AEs collected from Day1 through Day 7 after any vaccination; serious adverse events (SAEs), AEs leading to withdrawal and medically attended AEs were collected throughout the study period (Day1-Day 91).

Analysis was done on the Unsolicited Safety Set (all subjects in the exposed set with postvaccination unsolicited AE records).

Posted

Number

participants

At Day1 through Day 7 after any vaccination and throughout the study period (Day 1 to Day 91)

ID	Title	Description
OG000	CompDef	Subjects aged ≥ 2 to ≤ 17 years with complement deficiencies received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG001	Asplenia	Subjects aged ≥ 2 to ≤ 17 years with Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG002	CompDef + Asplenia	Subjects aged ≥ 2 to ≤ 17 years with either complement deficiencies or Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.
OG003	Healthy

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	CompDef	Subjects aged ≥ 2 to ≤17 years with complement deficiencies received 2 doses of rMenB+OMV NZ administered 2 months apart.	1	40	39	40
EG001	Asplenia	Subjects aged ≥ 2 to ≤ 17 years with Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.	5	110	106	110
EG002	CompDef + Asplenia	Subjects aged ≥ 2 to ≤17 years with either complement deficiencies or Asplenia received 2 doses of rMenB+OMV NZ administered 2 months apart.	6	150	145	150
EG003	Healthy	Healthy subjects aged ≥ 2 to ≤ 17 years received 2 doses of rMenB+OMV NZ administered 2 months apart.	0	87	87	87
EG004	Total	Total number of Subjects	6	237	232	237

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
INTRACARDIAC THROMBUS	Cardiac disorders	18.1	Non-systematic Assessment	EG0000 affected40 at risk EG0011 affected110 at risk EG0021 affected150 at risk EG0030 affected87 at risk EG0041 affected237 at risk
APPENDICITIS	Infections and infestations	18.1	Non-systematic Assessment	EG0000 affected40 at risk EG0011 affected110 at risk EG0021 affected150 at risk EG003
GASTROENTERITIS SALMONELLA	Infections and infestations	18.1	Non-systematic Assessment	EG0000 affected40 at risk EG0011 affected110 at risk EG0021 affected150 at risk EG003
RESPIRATORY TRACT INFECTION VIRAL	Infections and infestations	18.1	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected110 at risk EG0021 affected150 at risk EG003
TONSILLITIS	Infections and infestations	18.1	Non-systematic Assessment	EG0000 affected40 at risk EG0011 affected110 at risk EG0021 affected150 at risk EG003
CONCUSSION	Injury, poisoning and procedural complications	18.1	Non-systematic Assessment	EG0000 affected40 at risk EG0011 affected110 at risk EG0021 affected150 at risk EG003
RESPIRATORY DISORDER	Respiratory, thoracic and mediastinal disorders	18.1	Non-systematic Assessment	EG0000 affected40 at risk EG0011 affected110 at risk EG0021 affected150 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
DIARRHOEA	Gastrointestinal disorders	18.1	Non-systematic Assessment	EG0005 affected40 at risk EG0014 affected110 at risk EG0029 affected150 at risk EG0034 affected87 at risk EG00413 affected237 at risk
NAUSEA	Gastrointestinal disorders	18.1	Non-systematic Assessment	EG0007 affected40 at risk EG00128 affected110 at risk EG00235 affected150 at risk EG003
VOMITING	Gastrointestinal disorders	18.1	Non-systematic Assessment	EG0003 affected40 at risk EG0010 affected110 at risk EG0023 affected150 at risk EG003
CRYING	General disorders	18.1	Non-systematic Assessment	EG0002 affected40 at risk EG0012 affected110 at risk EG0024 affected150 at risk EG003
FATIGUE	General disorders	18.1	Non-systematic Assessment	EG00011 affected40 at risk EG00155 affected110 at risk EG00266 affected150 at risk EG003
INJECTION SITE ERYTHEMA	General disorders	18.1	Non-systematic Assessment	EG00015 affected40 at risk EG00123 affected110 at risk EG00238 affected150 at risk EG003
INJECTION SITE INDURATION	General disorders	18.1	Non-systematic Assessment	EG00017 affected40 at risk EG00132 affected110 at risk EG00249 affected150 at risk EG003
INJECTION SITE PAIN	General disorders	18.1	Non-systematic Assessment	EG00037 affected40 at risk EG001103 affected110 at risk EG002140 affected150 at risk EG003
INJECTION SITE SWELLING	General disorders	18.1	Non-systematic Assessment	EG00014 affected40 at risk EG00128 affected110 at risk EG00242 affected150 at risk EG003
PYREXIA	General disorders	18.1	Non-systematic Assessment	EG00010 affected40 at risk EG0017 affected110 at risk EG00217 affected150 at risk EG003
ARTHRALGIA	Musculoskeletal and connective tissue disorders	18.1	Non-systematic Assessment	EG0007 affected40 at risk EG00125 affected110 at risk EG00232 affected150 at risk EG003
MYALGIA	Musculoskeletal and connective tissue disorders	18.1	Non-systematic Assessment	EG0008 affected40 at risk EG00131 affected110 at risk EG00239 affected150 at risk EG003
HEADACHE	Nervous system disorders	18.1	Non-systematic Assessment	EG00011 affected40 at risk EG00148 affected110 at risk EG00259 affected150 at risk EG003
SOMNOLENCE	Nervous system disorders	18.1	Non-systematic Assessment	EG0007 affected40 at risk EG0013 affected110 at risk EG00210 affected150 at risk EG003
EATING DISORDER	Psychiatric disorders	18.1	Non-systematic Assessment	EG0005 affected40 at risk EG0011 affected110 at risk EG0026 affected150 at risk EG003
IRRITABILITY	Psychiatric disorders	18.1	Non-systematic Assessment	EG0007 affected40 at risk EG0012 affected110 at risk EG0029 affected150 at risk EG003
RASH	Skin and subcutaneous tissue disorders	18.1	Non-systematic Assessment	EG00010 affected40 at risk EG0019 affected110 at risk EG00219 affected150 at risk EG003

ID	Term
D008589	Meningococcal Infections
D008581	Meningitis
D000081208	Hereditary Complement Deficiency Diseases

Ancestor Terms

ID	Term
D016870	Neisseriaceae Infections
D016905	Gram-Negative Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections
D000090862	Neuroinflammatory Diseases
D009422	Nervous System Diseases
D000081207	Primary Immunodeficiency Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007153	Immunologic Deficiency Syndromes
D007154	Immune System Diseases

Healthy subjects aged ≥ 2 to ≤ 17 years received 2 doses of rMenB+OMV NZ administered 2 months apart.

EG0041 affected237 at risk

EG00450 affected237 at risk

EG0043 affected237 at risk

EG00410 affected237 at risk

EG004112 affected237 at risk

EG00472 affected237 at risk

EG00475 affected237 at risk

EG004223 affected237 at risk

EG00474 affected237 at risk

EG00427 affected237 at risk

EG00450 affected237 at risk

EG00466 affected237 at risk

EG00494 affected237 at risk

EG00415 affected237 at risk

EG00414 affected237 at risk

EG00418 affected237 at risk

EG00425 affected237 at risk