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 |
1 - To demonstrate the non-inferiority of the immune response after a 4-dose series of MenACYW conjugate vaccine compared to a 4-dose series of MENVEO when given concomitantly with routine pediatric vaccines to infants and toddlers 6 weeks to 15 months of age. 2 - To demonstrate the non-inferiority of the immune response after 3 doses of MenACYW conjugate vaccine compared to 3 doses of MENVEO when given concomitantly with routine pediatric vaccines to infants at 2, 4, and 6 months of age. |
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E.2.2 | Secondary objectives of the trial |
1 - To demonstrate the non-inferiority of the immune responses of the routine pediatric vaccines administered concomitantly with MenACYW conjugate vaccine as compared with MENVEO to infants and toddlers 6 weeks to 18 months of age. 2 - To assess the antibody responses against meningococcal serogroups A, C, Y, and W after the administration of the 4th dose of MenACYW conjugate vaccine as compared with MENVEO® when both are given concomitantly with routine pediatric vaccines at 12 months of age. 3 - To assess the persistence of bactericidal antibodies at 12 months of age (prior to the 4th dose) in participants who previously received 3 doses of MenACYW conjugate vaccine or MENVEO® in infancy concomitantly with routine pediatric vaccines at 2, 4, and 6 months of age. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
An individual must fulfill all of the following criteria in order to be eligible for trial enrollment: 1 - Aged ≥ 42 to ≤ 89 days on the day of the first study visit 2 - Healthy infants as determined by medical history, physical examination, and judgment of the investigator 3 - Informed consent form has been signed and dated by the parent(s) or guardian, and an independent witness, if required by local regulations 4 - Subject and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures 5 - Infants who received the first dose of hepatitis B vaccine at least 28 days before the first study visit |
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E.4 | Principal exclusion criteria |
An individual fulfilling any of the following criteria is to be excluded from trial enrollment: 1 - Participation at the time of study enrollment or in the 4 weeks preceding the first trial vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure 2 - Receipt of any vaccine in the 4 weeks preceding the first trial vaccination or planned receipt of any vaccine in the 4 weeks before and/or following any trial vaccination except for influenza vaccination, which may be received at a gap of at least 2 weeks before or 2 weeks after any study vaccination. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines. 3 - Previous vaccination against meningococcal disease with either the trial 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). 4 - Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis A, measles, mumps, rubella, varicella; and of Haemophilus influenzae type b, Streptococcus pneumoniae, and /or rotavirus infection or disease 5 - Receipt of more than 1 previous dose of hepatitis B vaccine 6 - Receipt of immune globulins, blood, or blood-derived products since birth 7 - Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy; or longterm systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks) since birth 8 - Family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated 9 - Individuals with blood dyscrasias, leukemia, lymphoma of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems 10 - Individuals with active tuberculosis 11 - History of any Neisseria meningitidis infection, confirmed either clinically, serologically, or microbiologically 12 - History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, hepatitis A, measles, mumps, rubella, varicella; and of Haemophilus influenzae type b, Streptococcus pneumoniae, and /or rotavirus infection or disease 13 - At high risk for meningococcal infection during the trial (specifically, but not limited to, subjects with persistent complement deficiency, with anatomic or functional asplenia, or subjects travelling to countries with high endemic or epidemic disease) 14 - History of intussusception 15 - History of any neurologic disorders, including any seizures and progressive neurologic disorders 16 - History of Guillain-Barré syndrome 17 - Known systemic hypersensitivity to any of the vaccine components or to latex, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances, including neomycin, gelatin, and yeast 18 - Verbal report of thrombocytopenia contraindicating intramuscular vaccination in the investigator’s opinion 19 - Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the investigator’s opinion 20 - Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw 21 - 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 trial conduct or completion 22 - Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives 23 - Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 100.4°F [≥ 38.0°C]). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided 24 - Identified as a natural or adopted child of the investigator or employee with direct involvement in the proposed study
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E.5 End points |
E.5.1 | Primary end point(s) |
1 - Level of antibody titers against meningococcal serogroups A, C, Y, and W after 4 doses of meningococcal vaccine given concomitantly with routine vaccines ; Titers are measured by serum bactericidal assay using human complement (hSBA). 2 - Percentage of participants with antibody titers ≥ 1:8 against meningococcal serogroups A, C, Y, and W after 3 doses of meningococcal vaccine given concomitantly with routine vaccines ; Titers are measured by hSBA.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 : 30 days after the fourth meningococcal vaccination. 2 : 30 days after vaccination at 6 months of age. |
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E.5.2 | Secondary end point(s) |
1 - IgG antibodies against hepatitis B surface antigen (anti-HB) at concentrations ≥ 10 milli-international units (mIU) / mL after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after vaccination at 6 months of age). 2 - Anti polyribosyl-ribitol phosphate (PRP) antibody concentrations ≥ 0.15 and ≥ 1.0 µg/mL after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after vaccination at 6 months of age). 3 - Anti-poliovirus types 1, 2, and 3 antibody titers ≥ 1:8 after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after vaccination at 6 months of age). 4 - Anti-rotavirus serum IgA antibody concentrations with ≥ 3-fold rise over baseline after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after vaccination at 6 months of age). 5 - Anti-rotavirus serum IgA antibody geometric mean concentrations (GMCs) after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after vaccination at 6 months of age). 6 - Anti-pertussis (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], fimbriae types 2 and 3 [FIM]) antibody concentrations after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after vaccination at 6 months of age). 7 - Anti-pneumococcal antibody concentrations after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after vaccination at 6 months of age) ; Anti-pneumococcal antibodies against serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F will be measured. 8 - Anti-measles antibody concentrations ≥ 255 mIU/mL after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 12-month vaccination). 9 - Anti-mumps antibody concentrations ≥ 10 mumps antibody units/mL after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 12-month vaccination). 10 - Anti-rubella antibody concentrations ≥ 10 IU/mL after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 12-month vaccination). 11 - Anti-varicella antibody concentrations ≥ 5 glycoprotein enzyme-linked immunosorbent assay (gpELISA) units/mL after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 12-month vaccination). 12 - Anti-pneumococcal antibody concentrations after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 12-month vaccination). 13 - Anti-PRP antibody concentrations ≥ 1.0 µg/mL after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 15-month vaccination). 14 - Anti-poliovirus types 1, 2, and 3 antibody titers ≥ 1:8 after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 15-month vaccination). 15 - Anti-pertussis antibody concentrations (PT, FHA, PRN, and FIM) (seroresponse) after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 15-month vaccination). 16 - Level of antibody titers against meningococcal serogroups A, C, Y, and W. 17 - Percentage of participants with ≥ 4-fold rise in antibody titers against meningococcal serogroups A, C, Y, and W. 18 - Level of antibody titers against meningococcal serogroups A, C, Y, and W. 19 - Percentage of participants with antibody titers ≥1:4 and ≥ 1:8 against meningococcal serogroups A, C, Y, and W. 20 - Solicited injection site reactions and systemic reactions. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 , 2 , 3 , 5 , 7 : 30 days after vaccination at 6 months of age 4 , 6 : Day 0 (pre-vaccination) and 30 days after vaccination at 6 months of age 8 , 9 , 10 , 11 , 12 : 30 days after the 12-month vaccination 13 , 14 , 15 : 30 days after the 15-month vaccination 16 : Before and 30 days after the 12-month vaccination 17 : From pre-4th dose to post-4th dose 18 , 19 : 30 days after 6-month vaccination and before 12-month vaccination 20 : Within 7 days after vaccination |
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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 |
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 |
Puerto Rico |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 21 |