| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| The Novartis Meningococcal B Recombinant + OMV NZ Vaccine is intended for prevention of meninigitidis and/or septicemia caused by N. meningitidis serogroup B. The objective of the Novartis Meningococcal B Recombinant + OMV NZ Vaccine is to identify a vaccine candidate that is safe and 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 consistency of the three commercial lots will be demonstrated first, prior to combining the data from the three lots to evaluate overall immunogenicity following three doses of rMenB+OMV NZ.
-To show the consistency of immune response from 3 lots of rMenB+OMV NZ, by serum bactericidal activity geometric mean titer response (SBA GMTs), when administered to healthy infants at 2, 4 and 6 months of age, at 1 month after the third vaccination.
-To assess the immunogenicity of 3 doses of rMenB+OMV NZ (3 lots combined) given to healthy infants at 2, 4 and 6 months of age concomitantly with routine infant vaccines, by evaluation of the serum bactericidal activity (SBA), at 1 month after the third vaccination.
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| E.2.2 | Secondary objectives of the trial |
-To assess the consistency of immune response from 3 lots of rMenB+OMV NZ, as measured by percentage of subjects with SBA titer ≥ 1:5 when administered to healthy infants at 2, 4 and 6 months of age, at 1 month after the third vaccination.
-To demonstrate that the immunogenicity of routine infant vaccines when given concomitantly with rMenB+OMV NZ at 2, 4 and 6 months of age, is non-inferior to that of routine infant vaccines given without rMenB+OMV NZ.
-To assess the prevalence of meningococcal B antibodies over the study period by evaluation of the serum bactericidal activity (SBA), at baseline and at 1 month after the third vaccination, in the subjects that received routine infant vaccines without rMenB+OMV NZ.
-To characterize the immune response against vaccine antigen 287-953, as measured by ELISA, at 1 month after the third vaccination.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. healthy 2-month old infants (55-89 days, inclusive), who were born after full term pregnancy with an estimated gestational age ≥ 37 weeks and a birth weight ≥ 2.5 kg;
2. for whom a parent/legal guardian has given written informed consent 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 and clinical judgment of the investigator.
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| E.4 | Principal exclusion criteria |
1. History of any meningococcal B or C vaccine administration;
2. Prior vaccination with any Diphtheria, Tetanus, Pertussis (acellular or whole cell), Polio (either Inactivated or Oral), Haemophilus influenzae type b (Hib), and Pneumococcal antigens;
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 rectal temperature >/= 38°C within the previous day;
7. Antibiotics within 6 days prior to enrollment;
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 since birth;
10. Family members and household members of research staff
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary
-Immunogenicity of the 3 lots of rMenB+OMV NZ will be considered equivalent if, for each of the 3 strains and each pair of vaccine lots, the two-sided 95% CI on the ratio of GMTs at 1 month after the third vaccination is contained within the interval [0.50, 2.00].
-Bactericidal activity (% ³1:5, i.e. percentage of subjects with SBA titer ³1:5) 30 days following the third vaccination (receiving either rMenB+OMV NZ (Lot 1, Lot 2 and Lot 3) .The immune response for the for the Norwegian strain H44/76 New Zealand strain NZ98/254 and 5/99 strain will be sufficient if the lower limit of the 95% CI for the % ³1:5 for the three lots combined is ³70%.
The success criteria for this study is a composite based on the two co-primary objectives. The first objective is to demonstrate that the SBA response of the three commercial lots are equivalent following the third dose of rMenB+OMV NZ. Once this objective is achieved, the data from the three lots will be combined and the sufficiency of the overall SBA response post 3rd dose with rMenB+OMV NZ will be demonstrated. Novartis will consider this study a success if, for each of the serogroup B reference strains and for each pair of vaccine lots, the two-sided 95% CI of the ratio of SBA GMTs at one month following the third vaccination is contained within the interval [0.5, 2.00]; and for each of the serogroup B reference strains, the lower limit of the 95% CI for the percentage of subjects with SBA titers % ³1:5 at one month post-dose 3 is ³ 70%.
Secondary
-Immunogenicity of the 3 lots of rMenB+OMV NZ will be considered equivalent if, for each of the 3 strains and each pair of vaccine lots, the two-sided 95% CI on the difference of percentage of subjects with SBA titer ³1:5 at 1 month after the third vaccination is contained within the interval [-10%, 10%].
-To assess the prevalence of meningococcal B antibodies over the study period by evaluation of the serum bactericidal activity (SBA), at baseline and at 1 month after the third vaccination, in the subjects that received routine infant vaccines without rMenB+OMV NZ.
-Characterization of immune response against vaccine antigen 287-953, as measured by ELISA, one month after the third dose, at 7 months of age.
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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 | Yes |
| 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 |
| immunogenicity and manufacturing consistency |
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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 | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| Open label and Observed blind |
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| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 6 |
| 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 | Yes |
| 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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| The End of Trial corresponds to the last visit of the last subject undergoing the trial (LSLV, Last Subject Last Visit) |
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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 | 1 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
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