E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy volunteers (Infections, Meningoccal) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
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 |
• To assess immunological non-inferiority of rMenB+OMV NZ and MenACWY when concomitantly administered compared to either alone in healthy infants at 3, 5, 7 and 13 months of age, as measured by the ratio of hSBA Geometric Mean Titers (GMTs) against each of the serogroup B indicator strains (for rMenB+OMV NZ) and serogroups A, C, W-135 and Y (for MenACWY) at one month after the fourth vaccination.
Non-inferiority will be concluded if, at one month following the fourth vaccination, the lower limits of the two-sided 95% confidence interval for the between-group ratios of GMTs (rMenB+OMV NZ + MenACWY versus rMenB+OMV NZ, and rMenB+OMV NZ + MenACWY versus MenACWY) is > 0.5 for all serogroup B indicator strains and all serogroups A, C, W-135 and Y.
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E.2.2 | Secondary objectives of the trial |
• To assess the immune response of rMenB+OMV NZ and MenACWY:
- at one month after the fourth vaccination,
- at one month after the third vaccination,
- at six months after the third vaccination,
when concomitantly administered compared to either alone in healthy infants at 3, 5, 7 and 13 months of age.
• To assess the safety and tolerability of rMenB+OMV NZ and MenACWY when concomitantly administered, compared to either alone, in infants at 3, 5, 7 and 13 months of age.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Healthy 3-month old infants (85-119 days, inclusive) at time of Visit 1 whose parents/legal guardians have given written informed consent after the nature of the study has been explained.
2. Available for all the visits scheduled in the study.
3. 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 previous immunization with a meningococcal vaccine or vaccine containing meningococcal antigen(s) at the time of enrollment.
2. Previous known or suspected disease caused by N. meningitidis.
3. Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis infection or colonization.
4. History of severe allergic reaction after previous vaccinations, or hypersensitivity to any component of the vaccine.
5. Known or suspected autoimmune disease or impairment/alteration of the immune system resulting from, for example:
- Chronic administration of immunosuppressants or other immune-modifying drugs since birth (3 months prior). (For corticosteroids, this means prednisone, or equivalent, ≥ 0.5 mg/kg/day or ≥ 10 mcg/day for children below 2 years. Inhaled and topical steroids are allowed),
- Immune deficiency disorder, or known HIV infection.
6. Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation since birth.
7. History of any progressive or severe neurologic disorder, or seizure disorder or Guillan Barré syndrome (exception: one self-limited febrile seizure is acceptable).
8. History of any bleeding disorder considered as a contraindication to intramuscular injection or blood draw.
9. Child's parent(s) or legal guardian(s) are not able to comprehend and to follow all required study procedures for the whole period of the study.
10. Receipt of any investigational or non-registered product since birth (3 month prior) or are expected to receive during the study period.
11. Family members or household members of site research staff.
12. Any clinically-significant chronic or progressive disease according to judgment of the investigator (pulmonary, cardiovascular, renal, hepatic or endocrine functional abnormality) or a congenital anomaly/known cytogenic disorder (e.g., Down’s syndrome).
13. History or any illness/condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) hSBA Geometric Mean Titers (GMTs) against each of the serogroup B indicator strains (for rMenB+OMV NZ) and serogroups A, C, W-135 and Y (for MenACWY)
2) Between-group ratios of GMTs for rMenB+OMV NZ + Men-ACWY versus rMenB+OMV NZ (serogroup B indicator strains), and rMenB+OMV NZ +MenACWY versus MenACWY (serogroups A, C, W-135 and Y); non-inferiority will be concluded if, at one month following the fourth vaccination, the lower limit of the two-sided 95% confidence interval for the between-group ratios of GMTs (rMenB+OMV NZ + MenACWY versus rMenB+OMV NZ, and rMenB+OMV NZ + MenACWY versus MenACWY) is > 0.5 for all serogroup B indicator strains and all serogroups A, C, W-135 and Y.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) and 2): One month after the fourth vaccination
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E.5.2 | Secondary end point(s) |
1) Evaluation of immune response of rMenB+OMV NZ by hSBA GMTs against each of the serogroup B indicator strains
2) Evaluation of immune response of rMenB+OMV NZ by per-centage of subjects with hSBA ≥1:5 and hSBA ≥1:8 against each of the serogroup B indicator strains
3) Evaluation of immune response by hSBA GMTs against each of the serogroups A, C, W-135 and Y
4) Evaluation of immune response by the percentage of subjects with hSBA ≥1:4 and subjects with hSBA ≥1:8 against each of the serogroups A, C, W-135 and Y
5) Within-subject Geometric Mean Ratios (GMRs) against each of the serogroup B indicator strains and each of the serogroups A, C, W-135 and Y
6) Percentage of subjects with four-fold increases in hSBA titers against each of the serogroup B indicator strains and each of the serogroups A, C, W-135 and Y
7) Frequencies and percentages of subjects with solicited local and systemic Adverse Events (AEs).
8) Frequencies and percentages of subjects with any other (unso-licited) AEs, AEs leading to withdrawal and medically attended AEs
9) Frequencies and percentages of subjects with SAEs, AEs leading to withdrawal and medically attended AEs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1), 2), 3), and 4): Before the first vaccination, one month after the third vaccination, before the fourth vaccination (13 months of age) and one month after the fourth vaccination
5) One month after the fourth vaccination versus pre-fourth vaccination
6) One month after the fourth vaccination over pre-fourth vaccination
7) and 8): 7 days (including the day of vaccination) after Day 1, 61, 121, and 301 for all Vaccine Groups
9) Throughout the study period (approximately 11 months) |
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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 | 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) | 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 | 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.8.2 | 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.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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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End of study is defined as the completion of the testing of such biological samples, to be achieved no later than 8 months after collection of the last biological sample visit 8. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 13 |