| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
The Novartis Meningococcal B recombinant vaccine is intended for prevention of meningitis and/or septicemia caused by Neisseria meningitidis serogroup B.
The objective of the Novartis Meningococcal B Recombinant Vaccine program is to identify vaccine candidates that are safe and that provide functional immune responses against heterologous meningococcal B strains.
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| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The present study, V72P6E1, is an extension of V72P6. The primary objective of this extension study will be to explore antibody persistence at approximately 40 months of age in subjects who received rMenB or rMenB+OMV NZ at 2, 4, 6 and 12 months of age in parent study V72P6. |
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| E.2.2 | Secondary objectives of the trial |
To explore bactericidal antibody persistence in children at 40 months of age who received one dose of rMenB±OMV NZ at 12 months of age in parent study V72P6.To characterize bactericidal antibody response of a booster dose of rMenB±OMV NZ administered at 40 months of age to children who received four doses of the same vaccine in V72P6.To characterize antibody responses of one and two booster doses of rMenB±OMV NZ administered at 40 and 42 months of age to children who received one dose of the same vaccine in V72P6.To assess the antibody response of a two-dose catch-up regimen of rMenB+OMV NZ administered to naïve children at 40 and 42 or at 60 and 62 months of age.To explore antibody persistence in children at 60 months of age who received one or two booster doses of rMenB±OMV NZ, or a two-dose catch-up regimen of rMenB+OMV NZ starting at 40 months of age in this study.For all immunogenicity objectives, responses will also be determined to vaccine antigen 287-953 by ELISA.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Informed consent must be obtained for all the subjects before enrollment into the study after the nature of the study has been explained.
Inclusion Criteria for naive subjects, newly enrolled (Groups V and VI):
Healthy male and female subjects will be recruited at the same study site.
1. Group V: Healthy 40 to 44-months-old children;
Group VI: Healthy 60 to 62-months-old children.
The age windows are defined as the first day the subject turns 40 or 60 months of age up to the day before the subject turns 45 or 63 months of age, respectively.
2. For whom parent(s)/legal guardian(s) have given written informed consent according to local regulations after the nature of the study has been explained;
3. Available for all the visits scheduled in the study;
4. In good health as determined by medical history, physical examination, clinical judgment of the investigator.
Inclusion Criteria for follow-on participants (Groups I, II, III and IV):
1. Healthy 40 to 44-months-old children.
The age window is defined as the first day the subject turns 40 months of age up to the day before the subject turns 45 months of age.
2. Who participated and completed the study V72P6;
3. For whom parent(s)/legal guardian(s) have given written informed consent after the nature of the study has been explained;
4. Available for all the visits scheduled in the study;
5. In good health as determined by medical history, physical examination, clinical judgment of the investigator.
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| E.4 | Principal exclusion criteria |
Exclusion Criteria for naïve subjects newly enrolled (Groups V and VI):
1. subjects whose parent(s)/legal guardian(s) are unwilling or unable to give written informed consent to participate in the study;
2. history of any meningococcal B vaccine administration;
3. previous ascertained or suspected disease caused by N. meningitidis;
4. household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis;
5. history of severe allergic reaction after previous vaccinations or hypersensitivity to any vaccine component
6. significant acute or chronic infection within the previous 7 days or axillary temperature 38C within the previous day;
7. antibiotics treatment within 7 days prior to enrollment, or within 14 days prior to enrollment if once-a-day treatment regimen;
8. any serious chronic or progressive disease according to the judgment of the investigator (e.g., neoplasm, diabetes mellitus Type I, cardiac disease, hepatic disease, progressive neurological disease or seizure, either associated with fever or as part of an underlying neurological disorder or syndrome, autoimmune disease, HIV infection or AIDS, or blood dyscrasias or diathesis, signs of cardiac or renal failure or severe malnutrition);
9. known or suspected impairment/alteration of the immune system, immunosuppressive therapy, use of systemic corticosteroids or chronic use of inhaled high-potency corticosteroids within 30 days prior to enrollment (use of low or moderate doses of inhaled steroids is not an exclusion);
10. receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation within 90 days prior to enrollment;
11. receipt of, or intent to immunize with any other vaccine(s) within 30 days prior and after any vaccination with the investigational vaccines (exception: flu-vaccines should not be administered within 14 days prior and after any vaccination with the investigational vaccines);
12. participation in another clinical trial within 90 days prior to enrollment or planned for during study;
13. family members and household members of research staff;
14. any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
Exclusion Criteria for follow-on participants (Groups I, II, III and IV) are the same as for Groups V and VI, with the exception of criterion 2.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Immunogenicity: Serum bactericidal activity will be measured against N. meningitidis serogroup B indicator strains H44/76, 5/99 and NZ98/254. Data will be summarized by calculating SBA geometric mean titers (GMTs), percentage of subjects with SBA titers ≥1:4 and ≥1:8, and percentage of subjects with four-fold increase over baseline. Antibody responses to vaccine antigen 287-953 will be determined by ELISA and summarized by geometric mean concentrations (GMCs) and four-fold rises.
Antibody persistence and immune responses will be interpreted using data from the naïve groups of children recruited at 40 and 60 months of age, as indicated below.
- Baseline antibody levels measured in naïve subjects at 40 months of age (Group V) will serve as a descriptive comparator to evaluate antibody persistence at 40 months of age for Groups I through IV.
- Responses to the first and second catch-up doses of rMenB+OMV NZ administered to naïve subjects at 40 and 42 months of age (Group V) will serve as a descriptive comparator to evaluate booster responses and, in turn, the presence of immunological memory in Groups I through IV.
- Baseline antibody levels measured in naïve subjects at 60 months of age (Group VI) will serve as a descriptive comparator to evaluate antibody persistence at 60 months of age post-boost in Groups I through IV and post-two catch-up doses in Group V.
Safety:All subjects who receive at least one dose of rMenB±OMV NZ investigational vaccine and provide some safety data post-vaccination with rMenB±OMV NZ (defined as the safety population) will be included in the safety and tolerability analyses.All safety analyses will be descriptive.Incidences of local reactions (i.e., pain, erythema, induration, swelling) and systemic reactions (i.e., fever [defined as axillary temperature ≥38°C], change in eating habits, sleepiness, irritability, vomiting, diarrhea, arthralgia, headache and rash) occurring during the 7 days following each study vaccination will be summarized by maximal severity and study group. Additionally, the numbers of subjects who used analgesic or antipyretic medication (prophylactically or therapeutically) within 7 days of study vaccination will be summarized.All AEs occurring during the 7 days following each study vaccination will be collected. SAEs as well as AEs that require a medical visit and/or result in premature withdrawal from the study will be collected throughout the study period, except for the 7 days after each vaccination with rMenB±OMV NZ in which all AEs will be collected.
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
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| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| Phase 2 Safety, Tolerability and Immunogenicity Trial |
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| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.1.7.1 | Other trial design description |
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| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
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| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| Last visit of the last subject undergoing the trial |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 25 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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