| 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 meningitidis and/or septicemia caused by N.meningitidis serogroup B. The objective of the Novartis Meningococcal B Recombinant + OMV vaccine is to identify a vaccine candidate that is safe and provide functional immune responses against heterologous meningococcal B strains. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10027276 |
| E.1.2 | Term | Meningococcal meningitis |
|
| 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 |
Immunogenicity Objective:
To demonstrate a sufficient immune response of rMenB+OMV NZ, when given concomitantly with routine infant vaccines to healthy infants at 2, 4 and 6 and 2, 3 and 4 months of age, as measured by percentage of subjects with serum bactericidal activitty (SBA) titer ≥1:5 at 1 month after the third vaccination.
Safety Objective:
To assess the safety and tolerability of 3 doses of rMenB+OMV NZ when given concomitantly with routine infant vaccines (i.e., combined DTaP-IPV-HBV-Hib vaccine and pneumococcal conjugate vaccine) at 2, 4 and 6 and 2, 3 and 4 months of age, or alone at 2, 4 and 6 months of age.
|
|
| E.2.2 | Secondary objectives of the trial |
1.To demonstrate that the immunogenicity of routine infant vaccine, when given concomitantly with rMenB+OMV NZ to healthy infants at 2, 3 and 4 months of age, is non-inferior to that of routine infant vaccines given without rMenB+OMV NZ.
2. To demonstrate that the immunogenicity of rMenB+OMV NZ when given concomitantly with routine infant vaccines is non-inferior to that of rMenB + OMV NZ given without routine infant vaccines at 2, 4 and 6 months of age.
3. To assess the prevalence of meningococcal B antibodies over the study period by evaluation of SBA, at baseline and at 1 month after the third vaccination, in the subjects that received routine infant vaccines without rMenB+ OMV NZ.
4. To characterize the immune response against vaccine antigen 287-953, as measured by ELISA, at 1 month after the third vaccination.
|
|
| 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.
|
|
| 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 axillary 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, insulin dependent 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. Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation.
11. Receipt of, or intent to immunize with any other vaccine(s) (with the exception of rotavirus), within 30 days prior and throughout the study period.
12. Participation in another clinical trial since birth 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.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
End points For Assessing Immunogenicity Objectives:
Bactericidal activity (% ≥1:5, i.e., percentage of subjects with SBA titer ≥1:5) 30 days following the third vaccination. The immune response will be sufficient for groups 1 (rMenB+OMV NZ + concomitant vaccines at 2, 4, 6 months of age) and 3 (rMenB+OMV + concomitant vaccines at 2, 3, 4 months of age) if the lower limit of the two-sided 95% confidence interval (CI) for the % ≥1:5 is ≥70% for the Norwegian strain H44/76, the New Zealand strain NZ98/254 and for strain 5/99.
End points For Assessing Safety Objectives:
serious adverse events and all other AEs including local and systemic reactions, and safety information obtained at all visits will be collected.
All subjects receiving at least one injection and providing post-baseline safety data will be included in the safety and tolerability analyses.
Local and Systemic Reactions. Incidences of local (i.e., injection site tenderness, erythema, induration, swelling) and systemic (i.e., fever [defined as axillary temperature ≥38°C], medically attended fever, change in eating habits, sleepiness, vomiting, diarrhea, irritability, unusual crying, rash) reactions occurring during the 7 days following each injection will be summarized by maximal severity and study group. In the analysis of safety criteria rectal measured temperature will be converted to axillary by subtracting 0.5 °C (38.0 °C axillary temperature corresponds to 38.5 °C rectal temperature). Additionally, the number of subjects who used antipyretic medication will be summarized, distinguishing between prophylactic and therapeutic use.
All local and systemic reactions but rash will be categorized as none, mild, moderate, and severe. If a reaction occurs more than once for a subject, the reaction will be classified according to the maximal severity.
Other Adverse Events. The original verbatim terms used by investigators to identify AEs in the case CRFs will be mapped to preferred terms using the MedDRA dictionary, version 10.1 or above. The adverse events will be grouped by MedDRA preferred terms into frequency tables according to system organ class (SOC). All reported AEs will be summarized according to system organ class and preferred term within each system organ class. When an AE occurs more than once for a subject, the maximal severity and strongest relationship to the vaccine will be counted. Additionally, three separate summaries of AEs will be generated as follows: (i) SAEs, (ii) AEs that are possibly or probably related to vaccine, and (iii) AEs that are unrelated to vaccine. Data listings of all AEs will be provided by subject. In addition, a summary of the primary termination reasons, a listing of subjects withdrawn from the study because of an AE, and a listing of all termination reasons will be presented.
|
|
| 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 | No |
| 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) | Yes |
| 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 | Yes |
| 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 | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 85 |
| 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
| |
| 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 | 18 |
| 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 | 18 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
