E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy volunteers (for active immunization against N. meningitidis serogroups A, C, W-135 and Y when given as a booster dose for the MenC and MenY antigens and as a priming dose for the MenA and MenW-135 antigens in toddlers 12 to 18 months of age who were primed in infancy with Hib-MenCY-TT and Pediarix® at 2, 4, and 6 months of age) |
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E.1.1.1 | Medical condition in easily understood language |
Inflammation of the brain and infection of the blood |
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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 | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028911 |
E.1.2 | Term | Neisseria meningitidis infection NOS |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10070124 |
E.1.2 | Term | Neisseria meningitidis test positive |
E.1.2 | System Organ Class | 100000004848 |
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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 |
• Immunogenicity of a booster dose of MenACWY-TT at 12–15 months of age
• Immunogenicity of a booster dose of MenACWY-TT co-administered with Infanrix® at 15-18 months of age
• Non-inferiority of the antibody responses to diphtheria and tetanus toxoid when Infanrix® is co-administered with MenACWY-TT at 15-18 months of age compared to Infanrix® administered alone at 15-18 months of age
• Non-inferiority of the antibody responses to pertussis toxoid, filamentous hemagglutinin, and pertactin when Infanrix® is co-administered with MenACWY-TT at 15-18 months of age compared to Infanrix® administered alone
• Non-inferiority of a booster dose of MenACWY-TT com-pared to HibMenCY administered at 12–15 months of age
• Non-inferiority of a booster dose of MenACWY-TT co-administered with Infanrix® at 15-18 months of age com-pared to HibMenCY when administered at 12–15 months of age |
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E.2.2 | Secondary objectives of the trial |
•Immunogenicity of Infanrix® given at 15-18 months of age after MenACWY-TT or Hib-MenCY-TT booster at 12-15 months compared to Infanrix® given alone at 15-18 months of age after 3-dose priming with Pediarix and ActHIB
•Immunogenicity of a booster dose of MenACWY-TT given at 12-15 months of age compared to MenACWY-TT co-administered with Infanrix® at 15-18 months of age one month after vaccination
•Safety of Hib-MenCY-TT co-administered with Pediarix as 3 primary doses from Day 0 after primary vaccination through Day 30 post-dose 3 and up to/excluding the first visit in the booster phase
•Safety of a booster dose of MenACWY-TT given at 12-15 months of age followed by Infanrix® and of MenACWY-TT co-administered with Infanrix® at 15-18 months of age compared to a booster dose of Hib-MenCY-TT given at 12-15 months of age followed by Infanrix® and compared to a dose of Infanrix® at 15-18 months of age from Day 0 after booster vaccination through six months after last booster vaccination |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects for whom the investigator believes that parents/guardians can and will comply with the requirements of the protocol.
• A male or female between, and including, 6 and 12 weeks of age (+ 6 days) at the time of the first vaccination.
• Written informed consent obtained from the parent or guardian of the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Born after 36 weeks gestation.
• For inclusion in the booster phase, subjects must have received all three doses in the primary phase |
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E.4 | Principal exclusion criteria |
Exclusion criteria for enrolment (primary phase)
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
• Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of study vaccine(s).
• Previous vaccination against Neisseria meningitidis, Haemophilus influenzae type b, diphtheria, tetanus, per-tussis, and/or poliovirus; more than one previous dose of hepatitis B vaccine.
• History of Neisseria meningitidis, hepatitis B, Haemophilus influenzae type b, diphtheria, tetanus, polio or pertussis diseases.
• Any confirmed or suspected immunosuppressive or im-munodeficient condition based on medical history and physical examination
• History of allergic disease or reactions likely to be exac-erbated by any component of the vaccines, or by dry natural latex rubber.
• Major congenital defects or serious chronic illness.
• History of any neurologic disorders or seizures.
• Acute disease at time of enrollment.
• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
• Concurrent participation in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
Exclusion criteria for enrolment (booster phase)
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding entry into the booster phase (Visit 4), or planned use during the study period.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
• Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days of entry into the booster phase (Visit 4) with the exception of Prevnar® and Hib (see the following three criteria) (Note; licensed influenza vaccine is allowed throughout the study)
• Planned administration/administration of a fourth dose of Prevnar® within 30 days of a booster dose of Infanrix®
• Previous administration of a booster dose of Hib prior to entry to the booster phase.
• Previous administration of a primary dose of Hib vaccine that is not part of the study protocol.
• Previous vaccination against Neisseria meningitidis that is not part of the study protocol.
• Previous vaccination with diphtheria, tetanus and pertussis antigens outside of the primary phase of the study.
• History of Neisseria meningitidis, Hib, diphtheria, tetanus or pertussis diseases.
• Any confirmed or suspected immunosuppressive or im-munodeficient condition based on medical history and physical examination.
• History of allergic disease or reactions likely to be exac-erbated by any component of the vaccines, or by dry natural latex rubber.
• Major congenital defects or serious chronic illness.
• History of any neurologic disorders or seizures.
• Acute disease at time of enrollment.
• Administration of immunoglobulins and/or any blood products within the past 3 months or planned administra-tion during the study period.
• Concurrent participation in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). |
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E.5 End points |
E.5.1 | Primary end point(s) |
• hSBA-MenA, hSBA-MenW-135, hSBA-MenC and hSBA-MenY titers above protocol specified cut-off
• hSBA-MenC and hSBA-MenY geometric mean titers (GMTs)
• hSBA-MenC and hSBA-MenY titers above protocol-specified cut-off
• Anti-diphtheria and anti-tetanus antibody concentrations above protocol-specified cut-off
• Anti-pertussis toxoid (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) geometric mean concentrations (GMCs) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• One month post vaccination with MenACWY-TT at 12-15 months of age; one month post vaccination with MenACWY-TT and Infanrix® at 15-18 months of age
• One month post vaccination with MenACWY-TT or Hib-MenCY-TT at 12-15 months of age; one month post vaccination with MenACWY-TT and Infanrix® at 15-18 months of age
• One month post vaccination with Hib-MenCY-TT at 12-15 months of age
• One month post vaccination with MenACWY-TT and Infanrix® or Infanrix® at 15-18 months of age
• One month post vaccination with MenACWY-TT and Infanrix® or Infanrix® at 15-18 months of age |
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E.5.2 | Secondary end point(s) |
• hSBA-MenC and hSBA-MenY antibody titers
• hSBA-MenA and hSBA MenW-135 GMTs and antibody titers
• hSBA-MenC and hSBA-MenY GMTs and titers
• Anti-diphtheria and anti-tetanus GMCs and seroprotection rates; Anti-PT, anti-FHA and anti-PRN concentrations
• hSBA-MenA and hSBA-MenW-135 GMTs; hSBA-MenA, hSBA-MenW-135, hSBA-MenC and hSBA-MenY antibody titers
• Anti-D and anti-T concentrations; Anti-PT, anti-FHA and anti-PRN GMCs
• Occurrence of solicited local and general symptoms
• Occurrence of unsolicited symptoms
• Serious adverse events and specific AEs of new onset of chronic illness(es), conditions prompting ER visits
• Serious adverse events and specific AEs of new onset of chronic illness(es), rash and/or conditions prompting emergency room (ER) visits |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• One month after vaccination with MenACWY-TT or Hib-MenCY-TT at 12-15 months of age
• One month after vaccination with MenACWY-TT at 12-15 months of age
• Prior to vaccination with MenACWY-TT and Infanrix® at 15-18 months of age
• One month after vaccination with Infanrix® at 15-18 months of age
• One month after vaccination with MenACWY-TT and Infanrix® at 15-18 months of age
• One month after vaccination with Infanrix® at 15-18 months of age in subjects vaccinated with MenACWY-TT or Hib-MenCY-TT at 12-15 months of age
• 8 days following each booster vaccination
• 31 days following each booster vaccination
• From the first primary study dose up to/excluding the first booster study dose
• From the first booster phase visit up to six months after the last 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 |
Immunogenicity, reactogenicity |
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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 | Yes |
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 | 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 |
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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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Last subject/last phone call |
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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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |