| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy volunteers (active immunization against invasive meningogoccal disease (IMD) caused by Meningococcal serogroups A, C, Y or W) |
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| E.1.1.1 | Medical condition in easily understood language |
Invasive meningococcal disease (IMD)
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| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10027274 |
| E.1.2 | Term | Meningococcal infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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| 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 demonstrate the non-inferiority of the antibody response against meningococcal serogroups A, C, Y, and W following the administration of a 3-dose series of MenACYW conjugate vaccine compared to a 3-dose series of a licensed meningococcal vaccine when each vaccine is given concomitantly with routine pediatric vaccines (10-valent pneumococcal vaccine and diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b [DTaP-IPV-HB-Hib vaccine]) to infants and toddlers 6 weeks to 18 months old |
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| E.2.2 | Secondary objectives of the trial |
- To demonstrate the non-inferiority of the antibody response against meningococcal serogroups A, C, Y, and W following the administration of 2 doses in infancy of MenACYW conjugate vaccine compared to 2 doses of a licensed meningococcal vaccine when each vaccine is given concomitantly with routine pediatric vaccines (10-valent pneumococcal vaccine and DTaP-IPV-HB-Hib vaccine) to infants and toddlers 6 weeks to 18 months old
- To describe the Ab responses against meningococcal groups A, C, Y, and W and the antigens of the routine pediatric vaccines administered in the study.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Aged ≥ 42 to ≤ 89 days on the day of the first study visit
- Healthy infants as determined by medical history, physical examination and judgment of the Investigator
- Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative (and by an independent witness if required by local regulations)
- Subject and parent/legally acceptable representative are able to attend all scheduled visits and to comply with all study procedures
- Covered by health insurance according to local regulations
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| E.4 | Principal exclusion criteria |
- Participation at the time of study enrollment (or in the 4 weeks preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
- Receipt of any vaccine in the 4 weeks preceding the first study vaccination or planned receipt of any vaccine in the 4 weeks before and/or following any study vaccination except for influenza vaccination and rotavirus vaccination, which may be received at a gap of at least 2 weeks before or 2 weeks after any study vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines. This exclusion criterion does not apply to subjects in Finland, Sweden or Poland who plan to receive the licensed rotavirus vaccine concomitantly with study vaccines at study vaccination visits V1 and V2.
- Receipt or planned to receipt during the study period vaccination against meningococcal disease with either the study vaccine or another vaccine (i.e., mono- or polyvalent, polysaccharide, or conjugate meningococcal vaccine containing serogroups A, C, Y, or W; or meningococcal B serogroup-containing vaccine)
- Previous vaccination against diphtheria, tetanus, pertussis, Haemophilus influenzae type B (Hib), poliovirus, Streptococcus pneumoniae, measles, mumps, or rubella. Previous vaccination against hepatitis B when administered to risk groups, as per local recommendation.
- Receipt of immune globulins, blood or blood-derived products since birth
- Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks) since birth
- Family history of congenital or hereditary immunodeficiency, unless the immune competence of the potential vaccine recipient is demonstrated
- Individuals with blood dyscrasias, leukemia, lymphoma of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems
- Individuals with active tuberculosis
- History of Neisseria meningitidis infection, confirmed either clinically, serologically, or microbiologically
- History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, measles, mumps, rubella, and of Haemophilus influenzae type b, and / or Streptococcus pneumoniae infection or disease
- At high risk for meningococcal infection during the study (specifically, but not limited to, subjects with persistent complement deficiency, with anatomic or functional asplenia, or subjects traveling to countries with high endemic or epidemic disease)
- Individuals with underlying conditions predisposing them to invasive pneumococcal disease (specifically, but not limited to, subjects with sickle cell disease or human immunodeficiency virus [HIV] infection)
- History of any neurologic disorders, including seizures and progressive neurologic disorders
- History of Guillain-Barré syndrome
- Known systemic hypersensitivity to any of the vaccine components, or history of a severe allergic reaction (e.g., anaphylaxis) to the vaccine(s) used in the study or to a vaccine containing any of the same substances including neomycin, streptomycin, polymyxin B, glutaraldehyde, formaldehyde, and gelatin
- Verbal report of thrombocytopenia, contraindicating intramuscular vaccination in the investigator’s opinion
- Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the investigator’s opinion
- Chronic illness (including, but not limited to, cardiac disorders, congenital heart disease, chronic lung disease, renal disorders, auto-immune disorders, diabetes, psychomotor diseases, and known congenital or genetic diseases) that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion
- Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives, including planning to leave the area of the study site before the end of the study
- Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided.
- Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw
- Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study
- Infants born preterm (by less than 37 weeks of gestation) requiring specific immunization schedule for routine childhood vaccines and/or specific care at the time of vaccination, as per national recommendations |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Antibody titers against meningococcal serogroups A, C, Y, and W (groups 1 and 2) - Antibody titers will be measured by the serum bactericidal assay using human complement (hSBA) and expressed as geometric mean titers (GMTs) |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
1. Antibody titers ≥ 1:8 against meningococcal serogroups A, C, Y, and W (groups 1 and 2) - % of participants achieving antibody titers ≥ predefined threshold of 1:8, measured by hSBA
2. Antibody titers above pre-defined thresholds for meningococcal serogroups A, C, Y, and W (all groups) - % of participants achieving antibody titers ≥ predefined thresholds, measured by hSBA
3. Antibody titers against meningococcal serogroups A, C, Y, and W (all groups) - Antibody titers will be measured by hSBA and expressed as GMTs
4. Antibody concentrations against pre-defined thresholds for antigens of DTaP-IPV-HB-Hib vaccine (all groups) - % of participants with antibody concentrations ≥ established seroprotection cut-off levels for diphtheria, tetanus, polio, hepatitis B and Hib, and seroresponse rate for anti-pertussis antibodies
5. Antibody concentrations/titers against antigens of DTaP-IPV-HB-Hib vaccine (all groups) - Antibody concentrations/titers will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations/titers (GMCs/GMTs)
6. Antibody concentrations above pre-defined thresholds for antigens of 10-valent pneumococcal vaccine (groups 1 and 2) - % of participants with antibody concentrations ≥ established seroprotection cut-off levels for antigens in the pneumococcal vaccine
7. Antibody concentrations against antigens of 10-valent pneumococcal vaccine (groups 1 and 2) - Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations (GMCs)
8. Antibody concentrations above pre-defined thresholds for antigens of 13-valent pneumococcal vaccine (group 3 and 4) - % of participants with antibody concentrations ≥ established seroprotection cut-off levels for antigens in the pneumococcal vaccine
9. Antibody concentrations against antigens of 13-valent pneumococcal vaccine (groups 3 and 4) - Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations (GMCs)
10. Antibody concentrations above pre-defined thresholds for antigens of MMR vaccine (all groups) - % of participants with antibody concentrations ≥ established seroprotection cut-off levels for antigens in MMR vaccine
11. Antibody concentrations against antigens of MMR vaccine (all groups) - Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. D0, 30 days after dose 2 and before and 30 days after the booster dose
2. 3. D0, 30 days after Dose 2 and before and 30 days after booster dose 3 for groups 1,2,3
D0, 30 days after dose 3 and before and 30 days after booster dose 4 for group 4
4. 5. D0 (only for Pertussis), 30 days after Dose 2 and before and 30 days after booster dose for groups 1,2 and 3
Before and 30 days after the booster for group 4
6. 7. 30 days after dose 2 and 30 days after booster dose
8. 30 days after dose 2, 30 days after booster dose 3 (group 3), or 30 days after booster dose 4 (group 4)
9. 30 days after dose 2 and 30 days after booster dose 3 (group 3) or 30 days after booster dose 4 (group 4)
10. 11. 30 days after the booster dose |
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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 | 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 | Yes |
| 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.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| 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 | No |
| 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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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 12 |
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