Safety and Immunogenicity of Novartis Meningococcal B Vac... | NCT01423084

Status Module

Name	Class
Novartis Vaccines	INDUSTRY

Oversight Module

Description 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
MenB Lot 1	Experimental	MenB vaccine Lot 1: 2 doses administered 1 month apart	Biological: Serogroup B meningococcal vaccine
MenB Lot 2	Active Comparator	MenB vaccine Lot 2: 2 doses administered 1 month apart	Biological: Serogroup B meningococcal vaccine

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Serogroup B meningococcal vaccine	Biological	All subjects will receive two rMenB+OMV NZ vaccinations one month apart and will be followed for a total of 2 months. Subjects will be randomized to 1 of 2 treatment arms to receive either two doses of rMenB+OMV NZ vaccine Lot 1 or two doses of rMenB+OMV NZ Lot 2. A total of 2 blood samples will be collected (at the first vaccination and 1 month after the 2nd vaccination). An additional blood draw will be collected in a subset of approximately 160 subjects (approximately 80 subjects in Group 1 and approximately 80 subjects in Group 2) at 2 weeks after the second vaccination

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) Against 3 Neisseria.Meningitidis (N. Meningitidis) Serogroup B Reference Strains.	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).	One month after the second vaccination (day 61)
ELISA Geometric Mean Concentration (GMCs) Against Vaccine Antigen 287-953	The immune response of two different lots of rMenB+OMV NZ is evaluated in terms of ELISA GMCs against vaccine antigen 287-953.	One month after the second vaccination (day 61)

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Subjects in Each Lot With hSBA ≥ 1:5	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	One month after the second vaccination (day 61)
Geometric Mean Ratio (GMR) of GMTs Against Each of N. Meningitidis Serogroup B Reference Strains.

Eligibility Module

Facility	Status	City	State	ZIP	Country	Contacts
Royal Children's Hospital		Herston	Queensland	4029	Australia
AusTrials Pty Ltd-Suites 6, 10 & 11, Peninsula Specialist Centre

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
26232542	Derived	Perrett KP, McVernon J, Richmond PC, Marshall H, Nissen M, August A, Percell S, Toneatto D, Nolan T. Immune responses to a recombinant, four-component, meningococcal serogroup B vaccine (4CMenB) in adolescents: a phase III, randomized, multicentre, lot-to-lot consistency study. Vaccine. 2015 Sep 22;33(39):5217-24. doi: 10.1016/j.vaccine.2015.06.103. Epub 2015 Jul 29.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
FG001	4CMenB_Siena	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
BG001	4CMenB_Siena	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000170 BG001174 BG002344

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

H44/76 strain

Title	Measurements
	OG000111(96 to 129) OG001111(96 to 128)

NZ98/254 strain

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Equivalence of 2 different lots of rMenB+OMV NZ in terms of hSBA GMTs against H44/76 strain					between groups ratio	1			2-Sided	95	0.82	1.23				Yes	Non-Inferiority or Equivalence	Two different lots of rMenB+OMV NZ are to be considered equivalent in terms of hSBA GMTs against H44/76 strain if the two sided 95% Confidence Interval (CI) between groups GMTs ratio at day 31 (ie, one month after the second vaccination) does not exceed the range 0.5 (lower limit) - 2.0 (higher limit).

Secondary

Percentage of Subjects in Each Lot With hSBA ≥ 1:5

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

Per Protocol Set population

Posted

Number

95% Confidence Interval

Percentage of subjects

One month after the second vaccination (day 61)

ID	Title	Description
OG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
OG001	4CMenB_Siena	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.

Units	Counts
Participants	OG000

Secondary

Geometric Mean Ratio (GMR) of GMTs Against Each of N. Meningitidis Serogroup B Reference Strains.

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).

Per Protocol Set Population

Posted

Geometric Mean

95% Confidence Interval

Ratio of GMTs

One month after the second vaccination (day 61)

ID	Title	Description
OG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
OG001	4CMenB_Siena	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.

Units	Counts
Participants	OG000

Secondary

Geometric Mean Ratio (GMR) of ELISA Geometric Mean Concentration (GMCs) Against Antigen 287-953

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).

Per Protocol Set Population

Posted

Geometric Mean

95% Confidence Interval

Ratio of GMTs

One month after the second vaccination (day 61)

ID	Title	Description
OG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
OG001	4CMenB_Siena	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.

Units	Counts
Participants	OG000

Secondary

hSBA GMT Against 3 N. Meningitidis Serogroup B Reference Strains at Day 45.

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.

Per Protocol Set, immunogenicity subset

Posted

Geometric Mean

95% Confidence Interval

Titers

Two weeks after the second vaccination (day 45)

ID	Title	Description
OG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
OG001	MenB Lot 2	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.

Units	Counts
Participants	OG000

Secondary

GMRs of GMT Against 3 N. Meningitidis Serogroup B Reference Strains at Day 45.

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.

Per Protocol Set, Immunogenicity subset

Posted

Geometric Mean

95% Confidence Interval

Ratio of GMTs

Two weeks after the second vaccination (day 45)

ID	Title	Description
OG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
OG001	4CMenB_Siena	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.

Units	Counts
Participants	OG000

Secondary

Percentage of Subjects With hSBA ≥1:5 Against Each of N. Meningitidis Serogroup B Reference Strains at Day 45.

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.

Per Protocol Population, immunogenicity subset

Posted

Number

95% Confidence Interval

Percentage of subjects

Two weeks after the second vaccination (day 45)

ID	Title	Description
OG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
OG001	4CMenB_Siena	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.

Units	Counts
Participants	OG000

Secondary

ELISA GMCs Against Vaccine Antigen 287-953 at Day 45.

The immune response of two different lots of rMenB+OMV NZ is evaluated in terms of ELISA GMCs against vaccine antigen 287-953.

Per Protocol Set, immunogenicity subset.

Posted

Geometric Mean

95% Confidence Interval

IU/ml

Two weeks after the second vaccination (day 45)

ID	Title	Description
OG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
OG001	4CMenB_Siena	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.

Units	Counts
Participants	OG000

Primary

ELISA Geometric Mean Concentration (GMCs) Against Vaccine Antigen 287-953

The immune response of two different lots of rMenB+OMV NZ is evaluated in terms of ELISA GMCs against vaccine antigen 287-953.

Per Protocol Set population

Posted

Geometric Mean

95% Confidence Interval

IU/ml

One month after the second vaccination (day 61)

ID	Title	Description
OG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
OG001	4CMenB_Siena	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.

Units	Counts
Participants	OG000

Secondary

GMR of ELISA GMCs Against Antigen 287-953 at Day 45.

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).

Per Protocol Set, immunogenicity subset

Posted

Geometric Mean

95% Confidence Interval

Ratio of GMTs

Two weeks after the second vaccination (day 45)

ID	Title	Description
OG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
OG001	4CMenB_Siena	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.

Units	Counts
Participants	OG000

Secondary

Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)

Number of subjects reporting solicited local and systemic Adverse Events and other indicators of reactogenicity after any vaccination.

Safety Set

Posted

Number

Number of subjects

From day 1 to day 7 after any vaccination

ID	Title	Description
OG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
OG001	4CMenB_Siena	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.

Units	Counts
Participants	OG000

Secondary

Number of Subjects Reporting Unsolicited AEs

Number of subjects reporting any Unsolicited AEs after any vaccination.

Safety Set

Posted

Number

Number of subjects

From day 1 to day 7 after any vaccination.

ID	Title	Description
OG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
OG001	4CMenB_Siena	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.

Units	Counts
Participants	OG000

Secondary

Number of Subjects Reporting SAEs and AE Leading to Withdrawal

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.

Safety Set

Posted

Number

Number of subjects

Throughout the study period.

ID	Title	Description
OG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.
OG001	4CMenB_Siena	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	4CMenB_Rosia	Subjects received two doses of rMenB+OMV NZ vaccine from lot 1 manufactured at Rosia facility.			0	169	165	169
EG001	4CMenB_Siena	Subjects received two doses of rMenB+OMV NZ vaccine from lot 2 manufactured at Siena facility.			0	173	171	173

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
injection site swelling	Investigations	MedDRA 14.1	Non-systematic Assessment	EG000115 events80 affected169 at risk EG001107 events74 affected173 at risk
Headache	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG000124 events75 affected169 at risk EG001159 events89 affected173 at risk
Fatigue	General disorders	MedDRA 14.1	Systematic Assessment	EG000129 events75 affected169 at risk EG001138 events85 affected173 at risk
injection site induration	General disorders	MedDRA 14.1	Non-systematic Assessment	EG00096 events65 affected169 at risk EG001107 events75 affected173 at risk
injection site erythema	General disorders	MedDRA 17.0	Systematic Assessment	EG000177 events111 affected169 at risk EG001175 events111 affected173 at risk
injection site pain	General disorders	MedDRA 17.0	Systematic Assessment	EG000337 events162 affected169 at risk EG001349 events170 affected173 at risk
nausea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG00068 events49 affected169 at risk EG00177 events56 affected173 at risk
rash	Skin and subcutaneous tissue disorders	MedDRA 17.0	Non-systematic Assessment	EG00013 events11 affected169 at risk EG00118 events16 affected173 at risk
arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Non-systematic Assessment	EG00038 events28 affected169 at risk EG00166 events45 affected173 at risk
myalgia	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG000169 events99 affected169 at risk EG001189 events118 affected173 at risk

Ancestor Terms

ID	Term
D016870	Neisseriaceae Infections
D016905	Gram-Negative Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections
D016920	Meningitis, Bacterial
D020806	Central Nervous System Bacterial Infections
D002494	Central Nervous System Infections
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D008581	Meningitis
D000090862	Neuroinflammatory Diseases

ID	Term
D008589	Meningococcal Infections
D008585	Meningitis, Meningococcal