| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Prophylaxis against bacterial meningitis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Bacterial infections caused by Neisseria meningitidis serogroups A, C, W and Y |
|
| 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 | 10027249 |
| E.1.2 | Term | Meningitis meningococcal |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 non-inferiority of the MenACWY liquid product aged for approximately 24 months to that of MenACWY vaccine,as measured by hSBA GMTs directed against N. meningitidis serogroup A at Day 29 after a single dose vaccination.
Criterion: Non-inferiority will be concluded if lower limit of the 2-sided 95% CI for ratio of hSBA GMTs against serogroup A between the MenACWY liquid vaccine aged for approximately 24 months and MenACWY vaccine is greater than 0.5.
• To demonstrate non-inferiority of the MenACWY liquid vaccine aged for approximately 30 months to that of MenACWY vaccine,as measured by hSBA GMTs directed against N. meningitidis serogroup A at Day 29 after a single dose vaccination.
Criterion: Non-inferiority will be concluded if lower limit of the 2-sided 95% CI for ratio of hSBA GMTs against serogroup A between the MenACWY liquid vaccine aged for approximately 30 months and the MenACWY vaccine is greater than 0.5. |
|
| E.2.2 | Secondary objectives of the trial |
•To compare the immunogenicity of the investigational MenACWY liquid product aged for approximately 24/30 months & currently licensed MenACWY vaccine, as measured by hSBA GMTs directed against N. meningitidis serogroups C, W and Y, at Day 29
•To compare the immunogenicity of the investigational MenACWY liquid product aged for approximately 24/30 months & currently licensed MenACWY vaccine,as measured by the percentage of subjects with a ≥ 4-fold rise in post vaccination hSBA titer for N. meningitidis serogroups A, C, W & Y at Day 29 compared to Day 1
•To compare the immunogenicity of the investigational MenACWY liquid product aged for approximately 24/30 months & currently licensed MenACWY vaccine,as measured by the percentage of subjects with hSBA titer ≥8 & ≥LLOQ directed against N. meningitidis serogroups A, C, W & Y at Day 29 • To assess the safety/reactogenicity of the investigational MenACWY liquid vaccine aged approximately 24/30 months and currently licensed MenACWY vaccine |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol or 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.
2. Written informed consent obtained from the subject/from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure.
3. Written informed assent obtained for subjects below legal age of consent, if required by local regulations at the time of the enrolment.
4. A male or female ≥10 to ≤40 YoA at the time of the vaccination.
5. Healthy subjects as established by medical history and clinical examination before entering into the study.
6. Female subjects of non-childbearing potential may be enrolled in the study.
Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause
7. Female subjects of childbearing potential may be enrolled in the study, if the subject:
- has practiced adequate contraception for 30 days prior to vaccination, and
- has a negative pregnancy test on the day of vaccination, and
- has agreed to continue adequate contraception during the entire treatment period. |
|
| E.4 | Principal exclusion criteria |
1. Child in care
2. Anaphylaxis following the administration of vaccine.
3. Any (clinical) condition that in the judgment of the investigator would make intramuscular injection unsafe & represents a contraindication to intramuscular vaccination and blood draws.
4. Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection.
5. Progressive, unstable or uncontrolled clinical conditions.
6. Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.
7. Hypersensitivity to the active substances or to any of the excipients of the vaccine, including diphtheria toxoid (CRM197), or a life-threatening reaction after previous administration of a vaccine containing similar components.
8. Abnormal function of the immune system resulting from:
- Clinical conditions.
- Systemic administration of corticosteroids within 90 days prior to informed consent, and until the Day 29 blood draw.
- Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent, and until the Day 29 blood draw.
9. Received immunoglobulins or any blood products within 180 days prior to informed consent.
10. Received an investigational or non-registered medicinal product within 30 days prior to informed consent.
11. Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study.
12. History of any meningococcal vaccination, with the exception of previous meningococcal C vaccination, if the last dose of MenC was received at ≤24 months of age.
13. Individuals who received any other vaccines within 7 days (for inactivated vaccines) or 14 days prior to enrolment in this study or who are planning to receive any vaccine within 28 days from the study vaccines.*
* In case an emergency mass vaccination for an unforeseen public health threat is organized by the public health authorities, outside the routine immunization program, the time period described above can be reduced if necessary for that vaccine provided it is licensed and used according to its Prescribing Information and according to the local governmental recommendations and provided a written approval of the sponsor is obtained.
14. Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
15. 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).
16. Current or previous, confirmed or suspected disease caused by N. meningitidis.
17. Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days prior to study vaccination.
18. Acute disease and/or fever within 3 days prior to study vaccination.
Note: enrolment may be postponed/delayed until such transient circumstances have ended.
- Fever is defined as body temperature >= 38.0°C/100.4°F. The preferred location for measuring temperature in this study will be the oral cavity.
- Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
19. Received systemic antibiotic treatment within 3 days prior to study vaccination or blood draw.
20. Study personnel as an immediate family or household member.
21. Pregnant or lactating women. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) against N. meningitidis serogroup A for each vaccine group and between-groups ratios |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1. GMTs against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group and between-groups ratios.
2. Within-group Geometric Mean Ratios (GMRs) of GMTs against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group.
3. Percentages of subjects with ≥4 fold rise in hSBA antibody titers for each of the N.meningitidis serogroups A, C,W and Y for each vaccine group and between-groups differences.
4. Percentages of subjects with hSBA antibody titers ≥8 and ≥LLOQ against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group and between groups differences.
5. Number of subjects reporting any unsolicited adverse events (AEs) within 30 min after vaccination.
6. Number of subjects reporting solicited local and systemic AEs.
7. Number of subjects reporting other indicators of reactogenicity.
8. Number of subjects reporting any unsolicited AEs.
9. Number of subjects reporting serious adverse events (SAEs), AEs leading to withdrawal and medically attended AEs. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At Day 1, and Day 29 (except serogroup A at Day 29).
2. At Day 29.
3. At Day 29.
4. At Day 1 and Day 29.
5. Within 30 min after vaccination at Day 1.
6. From Day 1 (6 hours) to Day 7 after vaccination .
7. From Day 1 to Day 7 after vaccination.
8. From Day 1 to Day 29 after vaccination.
9. From Day 1 to Day 181 (during the entire study period). |
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| 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 |
| Brazil |
| Estonia |
| Finland |
| France |
| Mexico |
| Russian Federation |
| South Africa |
| Spain |
| Turkey |
|
| 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
|
Last subject last visit (Phone call 3) or last testing results released of samples collected at Visit 2 (Day 29) of Study Phase 2* if it occurs after LSLV.
* In this case EoS must be achieved no later than 8 months after LSLV. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 28 |
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