E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 21.0 |
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 | 21.0 |
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 |
- To evaluate the immunogenicity of MenACWY-TT after administration of 1 dose in groups ACWY1d and ACWY2d or 2 doses in group ACWY2d with respect to Serum Bactericidal Assay using rabbit complement (rSBA) MenA/C/W-135/Y titres, 1 month after administration of MenACWY-TT in the ACWY1d and ACWY2d groups. - To evaluate the long-term persistence of the immune response induced by 1 or 2 doses of MenACWY-TT with respect to rSBA-MenA/C/W-135/Y titres, 1, 3 and 5 years after the last vaccination in the ACWY1d and ACWY2d groups. - To demonstrate the non-inferiority of the immune response to MenACWY-TT when co-administered with Prevenar 13 versus MenACWY-TT given alone 1 month after vaccination. - To demonstrate the non-inferiority of the immune response to Prevenar 13 when co-administered with MenACWY-TT versus Prevenar 13 given alone 1 month after vaccination. |
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E.2.2 | Secondary objectives of the trial |
-Immunogenicity of MenACWY-TT after 1 dose in groups ACWY1d and ACWY2d or 2 doses in group ACWY2d with respect to SBA using human complement (hSBA-MenA/C/W-135/Y) titres in a subset of subjects -Immunogenicity of MenACWY-TT after 1 dose with respect to rSBA-MenA/C/W-135/Y titres 1 month after administration in groups Co-ad and PCV-13 -Immune response to Prevenar 13 co-administered with MenACWY-TT or administered alone with respect to antibody concentrations and titres against pneumococcal antigens 1 month after administration in groups Co-ad and PCV-13 -Long-term antibody persistence with respect to hSBA and rSBA MenA/C/W-135/Y titres, 1, 3 and 5 years after last vaccination -Safety and reactogenicity in terms of solicited and unsolicited symptoms, serious adverse events (SAEs) and New Onset of Chronic Illnesses following each study vaccine dose -SAEs related to study vaccine administration and any event related to lack of vaccine efficacy, 1, 3 and 5 years after last vaccination |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects' parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply with the requirements of the protocol. • A male or female between, and including, 12 and 14 months of age at the time of the first vaccination. • Written informed consent obtained from the parent(s)/LAR(s) of the subject. • Healthy subjects as established by medical history and clinical examination before entering into the study. • Vaccination records showing the completion of the full primary vaccination schedule with Prevenar 13 and Diphtheria, Tetanus and Pertussis (DTP) containing vaccine according to local recommendations at least 5 months before the study entry. |
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E.4 | Principal exclusion criteria |
• Child in care. • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines 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 in total) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. • Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before and ending 30 days after the dose of vaccines, with the exception of a licensed inactivated influenza vaccine. Measles, Mumps Rubella (MMR) vaccine or Measles Mumps Rubella and Varicella (MMRV) vaccine can be co-administered with MenACWY-TT and/or Prevenar 13. A DTPa containing vaccine can be administered after the last blood sampling (at Visit 2 or 4 depending on the group). • Concurrently participating 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 vaccine/product (pharmaceutical product or device). • Previous vaccination against Neisseria meningitidis. • Previous booster vaccination against Streptococcus pneumoniae. • Previous booster vaccination against Corynebacterium diphtheriae, Clostridium tetani and Bordetella pertussis. • History of meningococcal disease. • Any confirmed or suspected immunosuppressive or immunodeficient condition (congenital or secondary), including human immunodeficiency virus (HIV) infection, based on medical history and physical examination. • Family history of congenital or hereditary immunodeficiency. • History of any reaction or hypersensitivity, including to diphtheria toxoid, likely to be exacerbated by any component of the vaccines. • Major congenital defects or serious chronic illness. • History of any neurological disorders or seizures, including Guillain-Barré syndrome (GBS). History of a simple, single febrile seizure is permitted. • Acute disease and/or fever at the time of enrolment. • Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titres ≥ 1:8. - Percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titres ≥ 1:8, ≥ 1:128 and titres in the ACWY1d and ACWY2d groups. - Anti-pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F antibody concentrations in the Co-ad and PCV-13 groups. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- rSBA titres ≥ 1:8: One month after administration of 1 dose of MenACWY-TT in the ACWY1d, ACWY2d and Co-ad groups and 2 doses in the ACWY2d group. - rSBA titres ≥ 1:8, ≥ 1:128 and titres: At Years 1, 3 and 5. - Pneumococcal antibody concentrations: One month after administration of Prevenar 13. |
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E.5.2 | Secondary end point(s) |
- Percentage of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY titres ≥ 1:4, ≥ 1:8 and titres. - Percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titres ≥ 1:8, ≥ 1:128 and titres in the PCV-13 group. - Percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titres ≥ 1:128 and titres in the ACWY1d, ACWY2d and Co-ad groups. - Percentage of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY titres ≥ 1:4, ≥1:8 and titres in a subset of subjects in the ACWY1d and ACWY2d groups. - Percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titres ≥ 1:8, ≥1:128 and titres in the Co-ad and PCV-13 groups - Percentage of subjects with anti-pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F antibody concentrations ≥ 0.15 µg/ml, ≥ 0.26 µg/ml and ≥ 0.35 µg/ml in the Co-ad and PCV-13 groups - Percentage of subjects with anti-pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F OPA titres ≥ 1:8 and titres in the Co-ad and PCV-13 groups. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- hSBA titres ≥ 1:4, ≥ 1:8 and titres: One month after administration of 1 dose of MenACWY-TT in a subset of subjects in the ACWY1d and ACWY2d groups and 2 doses in the ACWY2d group. - rSBA titres ≥ 1:8, ≥ 1:128 and titres: One month after administration of 1 dose of MenACWY-TT. - hSBA titres ≥ 1:4, ≥1:8 and titres and rSBA titres ≥ 1:8, ≥1:128 and titres: At Years 1, 3 and 5. - Pneumocococcal antibodies: One month after administration of Prevenar 13. |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Co-administration of MenACWY-TT with Prevenar13 versus administration of MenACWY-TT alone |
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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 | 29 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |