Clinical Trial Results:
A Phase 3b, Single-Center, Open-label Study to Assess the Immunogenicity and Safety of Novartis Meningococcal B Recombinant Vaccine When Administered at a 0, 2-Month Schedule in Healthy at-Risk Adults Aged 18 to 65 Years Inclusive.
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Summary
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EudraCT number |
2012-005815-25 |
Trial protocol |
DE |
Global end of trial date |
14 Apr 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
11 May 2016
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First version publication date |
03 May 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
V72_59
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01911221 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Vaccines and Diagnostics
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Sponsor organisation address |
Via Fiorentina 1, Siena, Italy, 53100
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Public contact |
Posting Director, Novartis Vaccines and Diagnostics, RegistryContactVaccinesUS@novartis.com
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Scientific contact |
Posting Director, Novartis Vaccines and Diagnostics, RegistryContactVaccinesUS@novartis.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Sep 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Apr 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Apr 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the immune response, serum bactericidal assay (hSBA) will be performed against the N. meningitidis serogroup B indicator strains H44/76, NZ98/254, 5/99 M10713 strain at one month after a vaccination course of two doses of rMenB+OMV NZ administered two months apart.
Characterisation of the immune response against vaccine antigen 287-953, as measured by ELISA at one month after a vaccination course of two doses of rMenB+OMV NZ administered two months apart.
To evaluate the safety and tolerability of two doses of rMenB+OMV NZ vaccine given two months apart, in healthy at-risk adults.
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Protection of trial subjects |
This clinical study was designed and was to be implemented and reported in accordance with the International Conference on Harmonisation (ICH) Tripartite Guidelines for Good Clinical Practices (GCP), with applicable local regulations including European Directive 2001/20/EC, Novartis Vaccines and Diagnostics codes on protection of human rights, and with the ethical principles laid down in the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Aug 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 13
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Worldwide total number of subjects |
13
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EEA total number of subjects |
13
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
13
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were recruited from single study center in Germany. | ||||||
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Pre-assignment
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Screening details |
All enrolled subjects were included in the trial. | ||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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rMenB+OMV NZ | ||||||
Arm description |
Subjects received two doses of rMenB +OMV NZ at 0 month and 2 month schedule. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
rMenB+OMV NZ
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Each dose 0.5 mL of injectable solution was administered intramuscularly.
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Baseline characteristics reporting groups
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Reporting group title |
rMenB+OMV NZ
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Reporting group description |
Subjects received two doses of rMenB +OMV NZ at 0 month and 2 month schedule. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
rMenB+OMV NZ
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Reporting group description |
Subjects received two doses of rMenB +OMV NZ at 0 month and 2 month schedule. | ||
Subject analysis set title |
All Enrolled Set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All screened subjects who provided informed consent and provided demographic and/or baseline screening assessments, regardless of the subject’s treatment status in the study and received a subject ID.
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Subject analysis set title |
Full Analysis Set (FAS)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All subjects in the enrolled set who received a study vaccination and provided an evaluable serum sample at 1 month after the second dose of rMenB+OMV NZ, with assay result available for at least 1 of the serogroup B indicator strains or M10713 strain or ELISA.
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Subject analysis set title |
Safety Set (Solicited AEs & other solicited reactions)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects in the exposed set who provided postvaccination reactogenicity data.
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Subject analysis set title |
Safety Set (unsolicited AEs)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects in the exposed set who had postvaccination unsolicited AE records.
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Subject analysis set title |
Safety Set (Overall)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects in the exposed set who had either postvaccination AEs or reactogenicity records.
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End point title |
1. Geometric Mean Human Serum Bactericidal Activity Titers Against N Meningitidis Serogroup B Strains Following A Two-dose Vaccination Schedule [1] | ||||||||||||||||||||||||
End point description |
The immunogenicity was assessed to evaluate the human serum bactericidal activity (hSBA) against the indicator strains of N meningitidis serogroup B (H44/76, 5/99, NZ98/254) and M10713 strain at baseline and at one month after the second vaccination.
Analysis was done on Full Analysis Set.
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End point type |
Primary
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End point timeframe |
Day 1 and Day 91
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analyses of immunogenicity and safety were descriptive. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
2. Geometric Mean Ratios Against N Meningitidis Serogroup B Strains Following A Two-dose Vaccination Schedule [2] | ||||||||||||||||
End point description |
The immunogenicity was assessed to evaluate the hSBA in terms of geometric mean ratios within subjects against the indicator strains of N meningitidis serogroup B (H44/76, 5/99, NZ98/254) and strain M10713 at one month after the second vaccination versus baseline.
Analysis was done on Full Analysis Set.
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End point type |
Primary
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End point timeframe |
Day 1 and Day 91
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analyses of immunogenicity and safety were descriptive. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
3. Percentages Of Subjects With hSBA≥ 1:5 Titers Against N Meningitidis Serogroup B Strains Following Two-Dose Vaccination Schedule. [3] | ||||||||||||||||||||||||
End point description |
The immunogenicity was assessed to evaluate the hSBA titers ≥ 1:5 in terms of percentages of subjects against N meningitidis serogroup B (H44/76, 5/99, NZ98/254) and strain M10713 following a two-dose vaccination schedule with rMenB+OMV NZ vaccine.
Analysis was done on Full Analysis Set.
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End point type |
Primary
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End point timeframe |
Day 1 and Day 91
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analyses of immunogenicity and safety were descriptive. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
4. Percentages Of Subjects With hSBA≥ 1:8 Titers Against N Meningitidis Serogroup B Strains Following Two-Dose Vaccination Schedule. [4] | ||||||||||||||||||||||||
End point description |
The immunogenicity was assessed to evaluate the human serum bactericidal activity titers ≥ 1:8 in terms of percentages of subjects against N meningitidis serogroup B (H44/76, 5/99, NZ98/254) and strain M10713 following a two dose vaccination schedule with rMenB+OMV NZ vaccine.
Analysis was done on Full Analysis Set.
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End point type |
Primary
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End point timeframe |
Day 1 and Day 91
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analyses of immunogenicity and safety were descriptive. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
5. Percentages Of Subjects With Four-Fold Increase In Human Serum Bactericidal Activity From Baseline Against N Meningitidis Serogroup B Strains Following a Two Dose Vaccination Schedule. [5] | ||||||||||||||||
End point description |
The antibody responses were assessed to evaluate the four fold increase in human serum bactericidal activity titers in terms of percentages of subjects against N meningitidis serogroup B (H44/76, 5/99, NZ98/254) and strain M10713 following a two dose vaccination schedule with rMenB+OMV NZ vaccine.
Analysis was done on Full Analysis Set.
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End point type |
Primary
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End point timeframe |
Day 91
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analyses of immunogenicity and safety were descriptive. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
6. Geometric Mean Concentrations For Vaccine Antigen 287-953 Following A Two-dose Vaccination Schedule [6] | ||||||||||||
End point description |
The antibody responses were assessed to evaluate the geometric mean concentrations as measured by Enzyme Linked Immunosorbent Assay (ELISA) in terms of percentages of subjects for the vaccine antigen 287-953 following a two dose vaccination schedule with rMenB+OMV NZ vaccine at baseline and at one month the second vaccination.
Analysis was done on Full Analysis Set.
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End point type |
Primary
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End point timeframe |
Day 1 and Day 91
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analyses of immunogenicity and safety were descriptive. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
7. Geometric Mean Ratios For Vaccine Antigen 287-953 Following A Two-dose Vaccination Schedule. [7] | ||||||||||
End point description |
The antibody responses were assessed to evaluate the geometric mean ratios as measured by ELISA within the subjects for the vaccine antigen 287-953 following a two dose vaccination schedule with rMenB+OMV NZ vaccine at one month after the second vaccination versus baseline.
Analysis was done on Full Analysis Set.
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End point type |
Primary
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End point timeframe |
Day 1 and Day 91
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analyses of immunogenicity and safety were descriptive. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
8. Percentages of Subjects With Four Fold Increase From Baseline For Vaccine Antigen 287-953 Following A Two-dose Vaccination Schedule. [8] | ||||||||||
End point description |
The antibody responses were assessed to evaluate the four fold increases in ELISA concentrations as measured by ELISA to the vaccine antigen 287-953 following a two dose vaccination schedule with rMenB+OMV NZ vaccine at one month the second vaccination over baseline.
Analysis was done on Full Analysis Set.
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End point type |
Primary
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End point timeframe |
Day 1 and Day 91
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analyses of immunogenicity and safety were descriptive. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
9. Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving rMenB+OMV NZ Vaccine ( After Any Vaccination) [9] | ||||||||||||||||||||||||||||||||||
End point description |
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving rMenB+OMV NZ Vaccine ( After Any Vaccination).
Analysis was done on Solicited Safety Set.
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End point type |
Primary
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End point timeframe |
Day 1 through Day 7 postvaccination.
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| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analyses of immunogenicity and safety were descriptive. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||
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End point title |
10. Number of Subjects Reporting Unsolicited Adverse Events After Receiving rMenB+OMV NZ Vaccine (After Any Vaccination) [10] | ||||||||||
End point description |
Safety was assessed as the number of subjects who reported unsolicited adverse events as collected from Day 1 to Day 91 following rMenB+OMV vaccination (a two dose schedule). Unsolicited adverse events were collected from day 1 through day 7 after each vaccination, while serious adverse events, medically attended adverse events and adverse events leading to withdrawal from study were reported from day 1 through day 91.
Analysis was done on Unsolicited Safety Set.
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End point type |
Primary
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End point timeframe |
Day 1 through Day 91 postvaccination
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| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analyses of immunogenicity and safety were descriptive. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
11. Number of Subjects Reporting Unsolicited Serious Adverse Events After Receiving rMenB+OMV NZ Vaccine (After Any Vaccination) [11] | ||||||||||||||||
End point description |
Safety was assessed as the number of subjects who reported Serious Adverse Events (SAEs), medically attended AEs, AEs leading to withdrawal from the study, as collected from day 1 to day 91 following vaccination with rMenB+OMV NZ (a two dose schedule ) were reported.
Analysis was done on Unsolicited Safety Set.
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End point type |
Primary
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End point timeframe |
Day 1 through Day 91 postvaccination.
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| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analyses of immunogenicity and safety were descriptive. |
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| No statistical analyses for this end point | |||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Day 1 through Day 91 postvaccination.
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Adverse event reporting additional description |
Safety was assessed as the number of subjects who reported Serious Adverse Events (SAEs), medically attended AEs, AEs leading to withdrawal from the study, as collected from day 1 to day 91 following vaccination with rMenB+OMV NZ (a two dose schedule) are reported.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
rMenB+OMV NZ
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Reporting group description |
Subjects received two doses of rMenB +OMV NZ at 0 month and 2 month schedule. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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25 Jun 2013 |
Addition of hSBA against the strain M10713 to evaluate the immunogenicity of rMenB+OMV NZ on the antigen NHBA (287-953), in addition to the ELISA. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
