| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy volunteers (Active immunization against IMD caused by Neisseria Meningitidis (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 |
Phase I:
•To evaluate the safety and reactogenicity of the 2 formulations of MenABCWY-2Gen vaccine
Phase II:
•To demonstrate the superiority of the effectiveness of MenABCWY-2Gen vaccine when administered at 0,2- or 0,6-months schedule, compared to the MenB vaccine administered at 0,6-months schedule
•To demonstrate the immunological non-inferiority (NI) of MenABCWY-2Gen vaccine administered at 0,2- or 0,6-months schedule compared to the MenACWY vaccine (single dose)†
•To evaluate the safety and reactogenicity of the MenABCWY-2Gen, the MenB and the MenACWY vaccines
Phase II-Sourcing:
•To evaluate the safety and reactogenicity of the 2 formulations of MenABCWY-2Gen vaccine
† The primary objective of immunological NI of MenABCWY-2Gen vaccine to MenACWY will be evaluated only in participants without a previous MenACWY vaccination (unprimed).All other primary and secondary objectives will be evaluated in participants with and without previous MenACWY vaccination (primed/unprimed) |
|
| E.2.2 | Secondary objectives of the trial |
Phase II-Formulation and Schedule-finding:
• To describe the distribution of participants by percentages of serogroup B invasive disease strains killed using enc-hSBA at 1 month after the last vaccination of the MenABCWY-2Gen vaccine administered at 0,2 and 0,6-months schedule and of the MenB vaccine administered at 0,6-months schedule
• To assess the immune response to the MenABCWY-2Gen vaccine administered at 0,2 and 0,6-months schedule and to the MenB vaccine administered at 0,6-months schedule against serogroup B indicator strains
• To assess the immune response to the MenABCWY-2Gen vaccine administered at 0,2 and 0,6-months schedule and to the MenACWY vaccine (single dose) against serogroups A, C, W and Y |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
All inclusion criteria are applicable for both study phases, except where specified otherwise.
• Participants and/or participants’ parent(s)/Legally Acceptable Representative(s) (LAR) who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the eDiaries, return for follow-up visits).
• Written or witnessed/thumb printed informed consent obtained from the participant or /parent(s)/LAR(s) of the participant prior to performance of any study specific procedure.
• Written informed assent obtained from the participant (if applicable) prior to performing any study specific procedure.
• Phase I only: A male or female between, and including, 18 and 40 years of age (i.e. 40 years + 364 days) at the time of the first study intervention administration.
• Phase II (Formulation and Schedule-finding) only: 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 study intervention administration.
• Phase II (Sourcing) only: A male or female between, and including, 18 and 50 years of age (i.e. 50 years + 364 days) at the time of the first study intervention administration.
• Participants 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).
• Healthy participants as established by medical history and clinical examination before entering into the study.
• Female participants 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 participants of childbearing potential may be enrolled in the study, if the participant:
- has practiced adequate contraception for 1 month prior to study intervention administration, and
- has a negative pregnancy test on the day of study intervention administration, and
- has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the study intervention administration. |
|
| 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.
• Are obese at enrolment (e.g. for participants from 20 years of age a body mass index (BMI) ≥ 30 kg/m2, for participants up to 19 years of age a BMI ≥ 95th percentile for age and gender or as applicable per country recommendations).
• Any neuroinflammatory (including but not limited to: demyelinating disorders, encephalitis or myelitis of any origin), congenital neurological conditions, encephalopathies, seizures (including all subtypes such as: absence seizures, generalised tonic-clonic seizures, partial complex seizures, partial simple 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 study interventions.
• Hypersensitivity, including allergy, to any component of vaccines, including diphtheria toxoid (CRM197) 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 (including, but not limited to: blood, endocrine, hepatic, muscular, nervous system or skin autoimmune disorders; lupus erythematosus and associated conditions; rheumatoid arthritis and associated conditions; scleroderma and associated disorders) or immunodeficiency syndromes (including, but not limited to: acquired immunodeficiency syndromes and primary immunodeficiency syndromes).
- Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 3 months prior to study vaccination until the last blood sampling visit for Phase I and Phase II (Sourcing) and Visit 5 (Day 211) for Phase II (Formulation and Schedule-finding). This will mean prednisone equivalent ≥20 mg/day for adult participants/ ≥0.5 mg/kg/day with maximum of 20 mg/day for paediatric participants. 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 other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.
Prior/Concomitant therapy
• Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) (Day -29 to Day 1), or their 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 3 months before the administration of the first dose of study intervention(s) or planned administration until the last blood sampling visit for Phase I and Phase II (Sourcing) and Visit 5 (Day 211) for Phase II (Formulation and Schedule-finding).
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first study intervention dose(s) until the last blood sampling visit for Phase I and Phase II (Sourcing) and Visit 5 (Day 211) for Phase II (Formulation and Schedule-finding). For corticosteroids, this will mean prednisone equivalent ≥20 mg/day for adult participants/ ≥0.5 mg/kg/day with maximum of 20 mg/day for paediatric participants. 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 participant has been or will be exposed to an investigational or a non-investigational intervention (drug/invasive medical device).
Other exclusions
• 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 dependents, family, or household member.
• Phase II (Formulation and Schedule-finding): Child in care. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1, 2. Percentages of participants with solicited administration site events in study Phase I (Safety Lead-in)
3, 4. Percentages of participants with solicited systemic events in study Phase I (Safety Lead-in)
5, 6. Percentages of participants with any unsolicited adverse events (AEs), including all serious adverse events (SAEs), AEs leading to withdrawal and AEs of special interest (AESIs) in study Phase I (Safety Lead-in)
7. Percentages of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase I (Safety Lead-in)
8. Percentages of participants with haematological and biochemical laboratory abnormalities, and changes from the baseline values, in study Phase I (Safety Lead-in)
9. Percentages of samples with bactericidal serum activity against a panel of 110 randomly selected endemic US N. meningitidis serogroup B invasive disease strains in study Phase II (Formulation and Schedule-finding)
10. Percentages of participants with a 4-fold rise in hSBA titers against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding)
11, 12, 13. Percentages of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding)
14, 15, 16. Percentages of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding)
17, 18, 19. Percentages of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding)
20. Percentages of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Formulation and Schedule-Finding)
21, 22, 23, 24. Percentages of participants with solicited administration site events in study Phase II (Sourcing)
25, 26, 27, 28. Percentages of participants with solicited systemic events in study Phase II (Sourcing)
29, 30, 31, 32. Percentages of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing)
33, 34, 35. Percentages of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Sourcing)
Timeframes:
1, 3, 11, 14, 21, 25. During the 7 days (including the day of vaccination) following vaccination at Day 1
2, 4, 22, 26. During the 7 days (including the day of vaccination) following vaccination at Day 31
5, 17, 29. During the 30 days (including the day of vaccination) following vaccination at Day 1
6, 30. During the 30 days (including the day of vaccination) following vaccination at Day 31
7, 33. Throughout the study period (Day 1 through Day 211)
8. At Day 8 after the first vaccination
9. At Day 211 (1 month after the last vaccination)
10. At 1 month after the vaccination schedule (i.e., Day 211 for the ABCWY groups and at Day 31 the Control group)
12, 15. During the 7 days (including the day of vaccination) following vaccination at Day 121
13, 16, 24, 28. During the 7 days (including the day of vaccination) following vaccination at Day 181
18. During the 30 days (including the day of vaccination) following vaccination at Day 121
19, 32. During the 30 days (including the day of vaccination) following vaccination at Day 181
20. Throughout the study period (Day 1 through Day 541)
23, 27. During the 7 days (including the day of vaccination) following vaccination at Day 61
31. During the 30 days (including the day of vaccination) following vaccination at Day 61
34. Throughout the study period (Day 1 through Day 241)
35. Throughout the study period (Day 1 through Day 361) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Due to the character limitation, timeframes for primary endpoints are added after the endpoints in section E.5.2. |
|
| E.5.2 | Secondary end point(s) |
1. Percentages of serogroup B invasive disease strains killed in each participant sample in study Phase II (Formulation and Schedule-finding)
2. Percentages of participants with hSBA titers ≥LLOQ for each and all serogroup B indicator strains in study Phase II (Formulation and Schedule-finding)
3. Percentages of participants with 4-fold rise in hSBA titers against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding)
4. hSBA Geometric mean titers (GMTs) against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding)
5. hSBA Geometric mean ratios (GMRs) against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding)
6. Percentages of participants with hSBA titers ≥ LLOQ for serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding)
7. Percentages of participants with a 4-fold rise in hSBA titers against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding)
8. hSBA GMTs against serogroups A, C, W and Y
9. hSBA GMRs against serogroups A, C, W and Y
10. Immunoglobulin G (IgG) antibodies against serogroups A, C, W and Y |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1,3.Day211(1 month[M] after the last vaccination[vacc])
2,4.Day1 in ABCWY(0,6-months[M]) &Control groups(gr), Day31 in ABCWY gr(0,2-M) &Day211 in all gr
5.Day211 in all gr vs Day1 in ABCWY(0,6-M) &Control gr &Day31 in ABCWY groups(0,2-M)
6.Day1 in ABCWY(0,6-M) &Control gr, Day31 in ABCWY gr(0,2-M&0,6-M), Day211 (1M after last vacc) in all ABCWY gr, &Day31 (1 M after MenACWY vacc) in Control gr
7.Day31(1M after first MenABCWY-2Gen vacc)
8.Day1 in ABCWY(0,6-M) &Control gr, Day31 in ABCWY gr(0,2-M&0,6-M), Day211 in all ABCWY gr, &Day31 in Control gr
9.Day31 vs Day1 in ABCWY(0,6-M) &Control gr, Day211 vs Day1 in ABCWY(0,6-M) gr &Day211 vs Day31 in ABCWY(0,2-M) gr
10.Day1 in ABCWY(0,6-M) &Control gr, Day31 in ABCWY gr(0,2-M) &Day31 in ABCWY(0,6-M) &in Control gr, &Day211 for all ABCWY gr |
|
| 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
Immunogenicity |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| 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 | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Observer-blind in Safety lead-in&Sourcing and partially blinded in Formulation and schedule finding |
|
| 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 | No |
| E.8.2.4 | Number of treatment arms in the trial | 15 |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| 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 |
| Brazil |
| United States |
| Finland |
| Poland |
| Sweden |
| Belgium |
| 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
|
| date of the last testing/reading released of the Human Biological Samples, related to primary and secondary endpoints; it must be achieved no later than 8 months after LSLV (Day 541, Month 18 in Phase II, formulation and schedule-finding). If the completion of testing occurs prior the completion of the LSLV the latter date defines the end of study visit. |
|
| 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 | |
| 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 | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
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