| 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.
This study is aimed at assessing the safety and immunogenicity of different doses and formulations (including decreasing OMV contents) of a Novartis Meningococcal B Recombinant Vaccine (rMenB + OMV NZ) in order to optimize its safety profile while maintaining sufficient immunogenicity. |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Immunogenicity Objectives
To assess if any of seven different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine induce sufficient immune response when given to healthy infants at 2, 3 and 4 months of age, as measured by percentage of subjects with serum bactericidal activity (SBA) titer ≥ 1:5, at 1 month after the third vaccination.
Safety Objectives
To assess if any of six different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine will reduce the incidence of fever ≥ 38.5 °C (rectal) occurring within 3 days (day 1–3) following first vaccination as compared to rMenB+OMV NZ.
|
|
| E.2.2 | Secondary objectives of the trial |
Immunogenicity Objectives
-To assess the immune response of seven different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine, as measured by SBA geometric mean titers (GMTs) titer, at 1 month after the third vaccination.
-To compare the immune response of rMenB+OMV NZ and of routine infant vaccines given with or without prophylactic antipyretic treatment.
Safety Objectives
-To assess if any of six different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine, will reduce the incidence of fever ≥ 38.5 °C (rectal) occurring within 3 days (day 1–3) following second and third vaccination and 7 days (day 1–7) following each vaccination as compared to rMenB+OMV NZ.
-To assess the incidence of fever ≥ 38.5 °C (rectal) following co-administration of routine infant vaccinations with Menjugate® or with each of seven formulations of rMenB+OMV NZ.
-To assess the safety and tolerability of each of seven different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects eligible to be enrolled in the study:
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 and for whom a parent/legal guardian is willing/able to comply with all protocol requirements;
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 or current 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 temperature ≥38°C within the previous day;
7. Oral or parenteral antibiotic treatment in the 7 days prior to the scheduled blood draw;
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 resulting from (for example):
a. Receipt of any immunosuppressive therapy at any time since birth
b. Receipt of immunostimulants at any time since birth
c. Use of systemic corticosteroids or chronic use of inhaled high-potency corticosteroids at any time 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 licensed vaccine(s) (with the exception of Rotavirus vaccines), from 28 days prior to enrollment to 28 days after the last study vaccination.
12. Receipt of any antipyretic medication in the previous 6 hours;
13. Participation in another clinical trial since birth or throughout study period;
14. Family members and household members of research staff;
15. Who have any history of seizure (one febrile seizure is not a reason for exclusion);
16. Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives;
17. Subject with any contraindication to treatment with paracetamol.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The immune response will be considered sufficient if the lower limit of the two-sided 95% confidence interval (CI) of the percentage of subjects with SBA ≥1:5 for N. meningitidis serogroup B is ≥65% for strains H44/76, NZ98/254 and 5/99.
Immunogenicity Endpoints
- percentage of subjects with SBA titer ≥ 1:5 to N. meningitidis serogroup B reference strains H44/76, NZ98/254 and 5/99 at one month after third vaccination.
- SBA GMTs at one month after third vaccination and geometric mean ratio (GMR) of one month post third vaccination GMTs over baseline to N. meningitidis serogroup B reference strains H44/76, NZ98/254 and 5/99.
- concomitant antigens: percentage of subjects with antibody response ≥ cut-offs for each antigen and Geometric Mean Concentrations (GMCs).
Safety Endpoints
The percentage of subjects with fever ≥ 38.5 °C (rectal temperature) within 3 days (day 1-3) after first vaccination.
- The percentage of subjects with fever, per 0.5 °C cumulative increments, within 3 days (day 1-3) after each vaccination.
- The percentage of subjects with solicited local reactions (i.e., injection site tenderness, erythema, induration and swelling) within 7 days (day 1-7) after each vaccination.
- The percentage of subjects with solicited systemic reactions (i.e., fever, change in eating habits, sleepiness, vomiting, diarrhea, irritability, unusual crying, rash, medically attended fever) within 7 days (day 1-7) after each vaccination.
- The percentage of subjects with unsolicited AEs within 7 days (day 1- 7) after each vaccination.
- The percentage of subjects with SAEs and AEs necessitating a medical office or Emergency Room (ER) visit and/or resulting in premature withdrawal of the subject from the study, throughout the study period.
|
|
| 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 | Yes |
| 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 |
|
| 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 |
| dose ranging and formulation finding |
|
| 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 | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.1.7.1 | Other trial design description |
| Partially Observer-Blind Randomized |
|
| 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.8.6 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
|
| The End of Trial corresponds to the last visit of the subject udergoing the trial (LSLV, Last Subject Last Visit) |
|
| 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 | 2 |
| 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 | 2 |
Print
