| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy volunteers (Active immunization against invasive disease caused by N. meningitidis serogroups A, B, C, W and Y) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Meningitis, Invasive meningococcal disease |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| 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 |
•Effectiveness of rMenB+OMV NZ and MenABCWY vaccines
-against a panel of N.meningitidis serogroup B strains at 1 month(M) after the 3 and 2-dose rMenB+OMV NZ series and last MenABCWY dose when compared to 1 M after MenACWY dose
-As the percentages of subjects whose sera kill ≥70% of strains tested using enc-hSBA at 1 M after the 3 and 2-dose rMenB+OMV NZ series and 1 M after last MenABCWY dose
•Lot-lot consistency of immune responses of 3 lots of MenACWY component of MenABCWY vaccine,as measured by hSBA GMTs at 1 M after last dose
•Immunological non-inferiority: MenABCWY versus MenACWY as measured by percentages of subjects achieving a 4-fold rise in hSBA titers at 1 M after last MenABCWY dose and 1 M after MenACWY dose
•Effectiveness non-inferiority: MenABCWY versus rMenB+OMV NZ in terms of percentage of samples with bactericidal serum activity at 1 M after last ABCWY dose and 1 M after 3 or 2 dose rMenB+OMV series
•Safety and reactogenicity of MenB,MenABCWY and MenACWY vaccines |
|
| E.2.2 | Secondary objectives of the trial |
•Immunological non-inferiority of MenABCWY compared to rMenB+OMV NZ as measured by the percentages of subjects achieving a 4-fold rise in hSBA titers against N.meningitidis serogroupB indicator strains at 1M after last MenABCWY dose & 1M after rMenB+OMV NZ dose
•Effectiveness of the rMenB+OMV NZ & MenABCWY vaccines against each of the N.meningitidis serogroup B invasive disease strains at 1M after 3&2-dose series & 1M after last MenABCWY dose versus 1M after MenACWY dose
•Distribution of subjects by percentages of serogroup B invasive disease strains killed at 1M after 3&2-dose series of rMenB+OMV NZ & 1M after last MenABCWY dose
•Immune response to
-rMenB+OMV NZ & MenABCWY vaccines against N.meningitidis serogroup B indicator strains at pre-vaccination & 1M after last MenABCWY dose & at 1M after 2&3-dose series of rMenB+OMV NZ
-MenABCWY and MenACWY vaccines against N.meningitidis serogroups A,C,W,Y at pre-vaccination & at 1M after first&last MenABCWY doses & 1M after MenACWY dose |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Subjects or/and 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.
• Written or witnessed/thumb printed informed consent obtained from the subject/parent(s)/LAR(s) of the subject prior to performance of any study specific procedure.
• Written informed assent obtained from the subject (if applicable) prior to performing any study specific procedure.
• A male or female between, and including, 10 and 25 years of age (i.e. 25 years + 364 days) at the time of the first vaccination.
• Healthy subjects as established by medical history physical examination and clinical judgment of the investigator before entering into the study.
• Subjects who are either unvaccinated with MenACWY vaccine or have received a single previous dose of MenACWY vaccine can participate in the study, if they have received it at least 4 years prior to informed consent and assent as applicable (with the exception of meningococcal C vaccination, if the last dose of MenC was received at ≤24 months of age).
• 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*.
• 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 until 30 days after completion of Visit 6.
* A female is considered to be of non-childbearing potential prior to menarche and after natural or induced menopause. Natural menopause is recognized to have occurred after 12 consecutive months of amenorrhea for which there is no other obvious pathological or physiological cause. Induced menopause is recognized to have occurred after hysterectomy, after bilateral oophorectomy, or iatrogenic ablation of ovarian function. |
|
| E.4 | Principal exclusion criteria |
Medical conditions
• Current or previous, confirmed or suspected disease caused by N. meningitidis.
• Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis infection within 60 days of enrolment.
• Progressive, unstable or uncontrolled clinical conditions.
• Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
• Any neuroinflammatory, congenital neurological conditions, encephalopathies, seizures. History of febrile convulsions should not lead to exclusion.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s)/product(s).
- Hypersensitivity, including allergy, to any component of vaccines, including diphtheria toxoid (CRM 197) and latex medicinal products or medical equipment whose use is foreseen in this study.
• Abnormal function or modification of the immune system resulting from:
- Autoimmune disorders or immunodeficiency syndromes.
- Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to study vaccination until the post-vaccination 3 blood sample (Visit 6). This will mean prednisone ≥20 mg/day (for adult subjects) or ≥0.5 mg/kg/day (for paediatric subjects), or equivalent. Inhaled and topical steroids are allowed.
- Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to study vaccination.
- Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
Prior/Concomitant therapy
• Use of any investigational or non-registered product other than the study vaccine(s)/product(s) during the period starting 30 days before the first dose of study vaccine(s)/product(s) (Day -29 to Day 1), or planned use during the study period.
• Previous vaccination against any group B meningococcal vaccine at any time prior to informed consent and assent as applicable.
• Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the first dose of study vaccine/ product or planned administration during the study period until the post-vaccination 3 blood sample (Visit 6).
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the vaccine/product dose(s) until the post-vaccination 3 blood sample (Visit 6). For corticosteroids, this will mean prednisone ≥20 mg/day (for adult subjects) or ≥0.5 mg/kg/day (for paediatric subjects), or equivalent. Inhaled and topical steroids are allowed.
Prior/Concurrent clinical study experience
• 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.
Other exclusions
• Child in care.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.
• History of /current chronic alcohol abuse and/or drug abuse as determined by the investigator.
• Any study personnel or immediate dependants, family, or household member. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Percentage of samples without bactericidal serum activity against each of the endemic US N. meningitidis serogroup B strains at 1 month after the 3-dose (0,2,6-M), the 2-dose [(0,6-M) and (0,2-M)] vaccination schedule of rMenB+OMV and 1 dose of MenACWY
2. Percentage of participants whose sera kill ≥70% of the strains tested using enc-hSBA at 1 month after the 3-dose schedule (0,2,6-M) and 2-dose schedule ([0,6-M] and [0,2-M]) of rMenB+OMV vaccine
3. Geometric mean titers (GMTs) against serogroups A, C, W and Y for each lot (ABCWY-1 Group, ABCWY-2 Group and ABCWY-3 Group) at 1 month after the last vaccination of MenABCWY
4. Percentage of participants with 4-fold rise in hSBA titers against N. meningitidis serogroups A, C, W and Y at 1 month after last MenABCWY vaccination (pooled lots) and MenACWY vaccination (for the ACWY Group), relative to baseline
5. Percentage of samples without bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the last MenABCWY dose (ABCWY group-pooled lots) and MenACWY vaccine (for ACWY group)
6. Percentage of samples with bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the last MenABCWY dose (pooled lots) and after 3-dose or 2-dose vaccination series of rMenB+OMV
7. Percentage of participants whose sera kill ≥70% of the strains tested using enc-hSBA at 1 month after the last vaccination in the ABCWY Group (pooled lots)
8. Percentage of participants with any solicited local adverse events (AEs)
9. Percentage of participants with any solicited systemic AEs
10. Percentage of participants with any unsolicited AEs, Serious Adverse Events (SAEs), AEs leading to withdrawal, AE of special interest (AESIs) and medically attended AEs
11. Percentage of participants with SAEs, AEs leading to withdrawal, AESIs and medically attended AEs |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. At 1M after vaccination schedule (Day[D] 211: MenB_0_2_6 group [3-dose], MenB_0_6 group, D91: MenB_0_2_6 group [2-dose], D31: ACWY group)
2. At 1M after vaccination schedule (D211: MenB_0_2_6 group [3-dose], MenB_0_6 group, D91: MenB_0_2_6 group [2-dose])
3,7. At D211
4, 5. At 1M after vaccination schedule (D211: ABCWY Group [pooled lots], D31: ACWY Group)
6. At 1M after vaccination schedule (D211: ABCWY Group [pooled lots], MenB_0_2_6 Group [3-dose], MenB_0_6 Group, D91: MenB_0_2_6 Group [2-dose])
8,9. During the 7 days (including the day of vaccination) after each vaccination (D1, D61, D181)
10. During the 30 days (including the day of vaccination) after each vaccination (D1, D61, D181)
11. Throughout the study period (D1 to D361) |
|
| E.5.2 | Secondary end point(s) |
1. Percentage of participants with 4-fold rise in hSBA titers against N.meningitidis serogroup B strains at 1 month after last MenABCWY dose (ABCWY group-pooled lots) and 1 month after 3-dose or 2-dose series of rMenB+OMV NZ in MenB groups, relative to baseline
2. Percentage of samples without bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after vaccination schedule in all groups
3. Percentage of participants classified by percentage of serogroup B invasive disease strains killed using enc-hSBA in each subject at 1 month after the 3-dose and 2-dose vaccination series of rMenB+OMV NZ and 1 month after last MenABCWY vaccine
4. Percentage of participants with hSBA titers ≥ LLOQ for each and all serogroup B indicator strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months and 0,2-months) and last MenABCWY (0,6-months)
5. Percentage of participants with 4-fold rise in hSBA titers for each of the serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months and 0,2-months) and MenABCWY (0,6-months), relative to baseline
6. hSBA GMTs against each of the N. meningitidis serogroup B strains at baseline and at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months and 0,2-months) and MenABCWY (0,6-months)
7. Geometric Mean Ratios (GMRs) for each of the N. meningitidis serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months and 0,2-months) and MenABCWY (0,6-months), relative to baseline
8. Percentage of participants with hSBA titers ≥ LLOQ for each of the N. meningitidis serogroups A, C, W and Y at Day 1 and 1 month after the first and after the last MenABCWY vaccination for ABCWY group (pooled lots) and 1 month after the MenACWY vaccine for ACWY group
9. Percentage of participants with 4-fold rise in hSBA titers for each of the N. meningitidis serogroups A, C, W and Y at 1 month after the first MenABCWY dose for the ABCWY Group (pooled lots) and 1 month after the MenACWY vaccine for ACWY Group
10. hSBA GMTs against each of the N. meningitidis serogroups A, C, W and Y at Day 1 and 1 month after the first and after the last MenABCWY vaccination for the ABCWY Group (pooled lots) and 1 month after the MenACWY vaccination for ACWY Group
11. GMRs for each of the N. meningitidis serogroups A, C, W and Y at 1 month after the first and after the last MenABCWY vaccination for the ABCWY Group (pooled lots) and 1 month after the MenACWY vaccination for ACWY Group
12. Immunoglobulin G (IgG) antibodies against N. meningitidis serogroups A, C, W and Y at Day 1 and 1 month after the first and after the last MenABCWY vaccination for ABCWY Group (pooled lots) and 1 month after the MenACWY vaccination for ACWY Group |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.1M after vaccination(vacc) schedule(sch)(D211:ABCWYgroup(gr)[pooled lots],MenB_0_2_6gr[3-dose],MenB_0_6gr,D91:MenB_0_2_6gr[2-dose])
2.1M after vacc sch(D211:MenB_0_2_6gr[3 dose],MenB_0_6gr,ABCWYgr[pooled lots],D91:MenB_0_2_6gr[2 dose],D31:MenACWYgr)
3.1M after vacc sch(D211:MenB_0_2_6gr[3 dose],MenB_0_6gr,ABCWYgr[pooled lots],D91:MenB_0_2_6gr[2 dose])
4,5,6.D1(pre-vacc)&1M after vacc sch(D211:MenB_0_2_6gr[3 dose],MenB_0_6gr,ABCWYgr[pooled lots],D91:MenB_0_2_6gr[2 dose])
7.1M after vacc sch(D211:MenB_0_2_6gr[3 dose],MenB_0_6gr,ABCWYgr[pooled lots],D91:MenB_0_2_6gr[2 dose])vsD1
8,10.D1&1M after vacc sch(D31:ABCWYgr[pooled lots-dose 1],ACWYgr,D211:ABCWYgr[pooled lots–dose 2])
9.D31vsD1
11,12.1M after vacc sch(D31:ABCWYgr[pooled lots-dose1],ACWYgr,D211:ABCWYgr[pooled lots–dose2]) vsD1 |
|
| 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 |
| Effectiveness and immunogenicity |
|
| 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 | No |
| E.8.1.5 | Parallel group | Yes |
| 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 | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 6 |
| 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 | 25 |
| 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 |
| Australia |
| Canada |
| Turkey |
| United States |
| Estonia |
| Finland |
| Czechia |
|
| 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
|
| the date of release of the last testing results, to be achieved not later than 8 months after LSLV (T7; Day 361). |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | 22 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 22 |
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