Clinical Trial Results:
A Phase 3b, Single-Center, Open-label Study to Assess the Safety of Novartis Meningococcal B Recombinant Vaccine When Administered at a 0, 2-Month Schedule in Healthy at-risk Adults.
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Summary
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EudraCT number |
2011-003694-29 |
Trial protocol |
IT |
Global end of trial date |
13 Nov 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Dec 2016
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First version publication date |
15 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_37
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01478347 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Sample data: Sample data | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma Services AG
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Sponsor organisation address |
Lichtstrasse 35, Basel, Switzerland, 4056
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Public contact |
Posting director, Novartis Pharma Services AG, RegistryContactVaccinesUS@novartis.com
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Scientific contact |
Posting director, Novartis Pharma Services AG, 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 |
09 Mar 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Nov 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 descriptively assess the safety of Novartis Recombinant Meningococcal B vaccine with Outer Membrane Vesicle from the New Zealand strain (rMenB+OMV NZ) in healthy at-risk adults when administered at a 0, 2-month schedule, throughout the clinical study.
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Protection of trial subjects |
This clinical study was designed, implemented and reported in accordance with the International Conference on Harmonization (ICH) Harmonized Tripartite Guidelines for Good Clinical Practice (GCP), with applicable local regulations (including European Directive 2001/20/EC, US Code of Federal Regulations Title 21, and Japanese Ministry of Health, Labor, and Welfare), 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 |
21 May 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 |
Italy: 18
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Worldwide total number of subjects |
18
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EEA total number of subjects |
18
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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) |
18
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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 a single center (Siena, Italy). | ||||||||||||||||||
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Pre-assignment
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Screening details |
All enrolled subjects participated in the study (n. 18 in part I and n. 12 subjects in part II of the study. However, in the safety set part II, n. 11 subjects were included since n. 1 was withdrawn after visit 3). | ||||||||||||||||||
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Period 1
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Period 1 title |
Visit 1 to Visit 7 (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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Are arms mutually exclusive |
No
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Arm title
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Visit 1 to Visit 3 | ||||||||||||||||||
Arm description |
Healthy adults (≥18 to ≤65 years) at high risk for meningococcal B disease, due to routine occupational exposure to Neisseria meningitidis cultures (e.g. lab workers), were administered two injections of rMenB+OMV NZ vaccine, two months apart, in part I of the study. | ||||||||||||||||||
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 in pre-filled syringe
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Routes of administration |
Intramuscular use
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Dosage and administration details |
The vaccine was administered by intramuscular (IM) injection into the deltoid region of the nondominant arm at a 0, 2-month vaccination schedule. The vaccine was supplied as a suspension for injection in a prefilled syringe (0.5 mL) containing 50 μg of each of the following 961c, 936-741, 287-953 N. Meningitidis purified antigens, 25 µg of OMV from N. meningitidis strain NZ 98/254, and 1.5 mg of aluminum hydroxide as adjuvant.
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Arm title
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Visit 4 to Visit 7 | ||||||||||||||||||
Arm description |
Healthy adults (≥18 to ≤65 years) at high risk for meningococcal B disease, due to routine occupational exposure to Neisseria meningitidis cultures (e.g. lab workers), who were administered two injections of rMenB+OMV NZ vaccine, two months apart, in part I of the study, were re-enrolled for optional blood draws and safety follow-up in part II of the study. | ||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Visit 1 to Visit 7
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Reporting group description |
Healthy adults (≥18 to ≤65 years), at high risk for meningococcal B disease due to routine occupational exposure to N. meningitidis cultures (e.g. lab workers), who had received two injections of rMenB+OMV NZ vaccine in the part I of this study were re-enrolled for optional blood draws and safety follow-up in part II of the study. | |||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Visit 1 to Visit 3
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Reporting group description |
Healthy adults (≥18 to ≤65 years) at high risk for meningococcal B disease, due to routine occupational exposure to Neisseria meningitidis cultures (e.g. lab workers), were administered two injections of rMenB+OMV NZ vaccine, two months apart, in part I of the study. | ||
Reporting group title |
Visit 4 to Visit 7
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Reporting group description |
Healthy adults (≥18 to ≤65 years) at high risk for meningococcal B disease, due to routine occupational exposure to Neisseria meningitidis cultures (e.g. lab workers), who were administered two injections of rMenB+OMV NZ vaccine, two months apart, in part I of the study, were re-enrolled for optional blood draws and safety follow-up in part II of the study. | ||
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End point title |
1. Number of subjects reporting unsolicited adverse events (AEs) following vaccination with two injections of rMenB+OMV NZ. [1] [2] | ||||||||||||||||||
End point description |
The number of subjects with serious adverse events (SAE), medically attended adverse events and AEs leading to premature withdrawal, following two injections of rMenB+OMV NZ vaccine are reported. This analysis was done on the safety set population i.e all subjects in the exposed set with unsolicited adverse event data for part I of the study.
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End point type |
Primary
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End point timeframe |
Day 1 through 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: No statistical analyses were performed for this endpoint. All the analyses were run descriptively. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analyses were performed for this endpoint. All the analyses were run descriptively. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
2. Number of subjects reporting unsolicited AEs during Safety Follow-up (Part II of the Study). [3] [4] | ||||||||||||||
End point description |
The number of subjects (who were administered with two injections of rMenB+OMV NZ vaccine in the part I of this study) reporting unsolicited AEs during the safety follow-up in part II of the study, are reported. Unsolicited AEs in part II of the study include AEs considered to be related to blood draw procedure and all SAEs. This analysis was done on the safety set population i.e all subjects in the exposed set with unsolicited adverse event data for part II of the study.
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End point type |
Primary
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End point timeframe |
Day 151 to day 331. Subject’s eligibility for participation in part II of this trial was confirmed starting from day 92 on. Next study visit (visit 4, day 151) was scheduled upon subject’s agreement to continue in the trial.
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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: No statistical analyses were performed for this endpoint. All the analyses were run descriptively. [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analyses were performed for this endpoint. All the analyses were run descriptively. |
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| Notes [5] - Of the 12 subjects enrolled for part II, one was withdrawn after Visit 3 (reason: lost to follow-up) |
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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 |
All serious AEs and other unsolicited AEs collected from Day 1 to Day 331 (throughout the study) for subjects who participated in both part I and II of the study, 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 |
17.1
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Reporting groups
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Reporting group title |
Visit 1 to Visit 7
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Reporting group description |
Healthy adults (≥18 to ≤65 years), at high risk for meningococcal B disease due to routine occupational exposure to N. meningitidis cultures (e.g. lab workers), were administered two injections of rMenB + OMV NZ vaccine, 2 months apart, in part I of the study. In part II of the study subjects were re-enrolled for optional blood draws and safety follow-up. | ||||||||||||||||||||
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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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13 Nov 2012 |
The amendment included the following changes:
- The trial was to be conducted in a single country.
- The maximum age for enrollment was extended to ≤ 65 years from ≤ 60 years in the original protocol.
- To specify the eligibility for enrollment of Novartis’ employees.
- The ‘at-risk’ subjects to be enrolled into this trial also included travelers to MenB epidemic area in the original protocol. According to the first amendment the travelers to these areas were not to be enrolled.
- The first protocol amendment also extended the study (to part II) to include additional blood draws from high responders to the study vaccine. |
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14 Dec 2012 |
It included changes to the study entry criteria:
- a subject could continue to participate in part II of the protocol if he had hematocrit value higher than 32% for female subjects or higher than 35% for male subjects. In the original protocol these were specified as hemoglobin not lower than 12.5 g/dL for females and 13.5 g/dL for males.
- For female subjects if sexually active, they were to use one of the accepted birth control methods at least 1 month prior to study entry rather than 2 months prior to study entry as mentioned in the original protocol. |
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17 Sep 2013 |
Information on marketing authorization was updated and duration of safety data collection period was clarified. |
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29 Jan 2014 |
It was specified that a urine pregnancy test had to be obtained only from female subjects of child bearing potential.
Written informed consent was explicitly required as part of the inclusion criteria in protocol part II. |
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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 | |||
