| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Invasive Meningococcal Disease (IMD) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Invasive Meningococcal Disease (IMD) |
|
| 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 | 10076061 |
| E.1.2 | Term | Meningococcal immunisation |
| E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
| 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 describe the safety profile of the SP MenB vaccine formulations and the 2 licensed MenB comparator vaccines in healthy adults, adolescents, toddlers and infants, when administered alone (Stages 1-4) or concomitantly with MenQuadfiTM (MenACYW conjugate vaccine) (for Stages 2-4 only), and with age-appropriated routine pediatric vaccines (for Stages 3-4 only)
• To describe the immune response to the SP MenB vaccine formulations and the 2 licensed MenB comparator vaccines after the last dose of primary vaccination in healthy adults, adolescents, toddlers and infants, when administered alone, or concomitantly with MenQuadfi Vaccine or other routine vaccines, as measured by the serum bactericidal assay using human complement (hSBA) in the primary panel of MenB strains by Stage, by age group and by vaccine schedule. |
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| E.2.2 | Secondary objectives of the trial |
•To describe the immune response to the SP MenB vaccine formulations and the 2 licensed MenB comparator vaccines at each timepoint in healthy adults, adolescents, toddlers and infants, when administered alone or concomitantly with MenQuadfi Vaccine or other routine vaccines
• To describe the immune response (breadth of coverage) in the secondary panel of MenB strains in participants (adults and adolescents)
• To describe the persistence of immune response following primary series at D366, and immune response 1 month after a booster dose of the SP MenB vaccine given 1-year post-dose 1 (at D366) in a subset of adults and adolescents in Stage 2 who received SP MenB vaccine formulations, Bexsero Vaccine or Trumenba Vaccine as measured by hSBA in the primary panel of MenB strains by age group
• To describe the immune response against meningococcal serogroups A, C, W and Y measured with hSBA in participants from each agegroup receiving MenQuadfi Vaccine
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- For US: Aged 10 to 25 years on the day of inclusion (“10-25 years” means from the day of the 10th birthday to the day before the 26th birthday)
- For EU: Aged 42 to 89 days or 12 to 18 months or 10 to 50 years on the day of inclusion (“42 to 89 days” means from 42 days after birth to the 89th day after birth; “12-18 months” means from the12th month after birth to the day before the 19th month after birth; “10-50 years” means from the day of the 10th birthday to the day before the 51st birthday
- Participants or participant and parent/legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures
- Covered by health insurance (applicable depending on local regulations)
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and judgement of the Investigator
- For adults: A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:
• Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, or surgically sterile
OR
• Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to the first study intervention administration until at least 4 weeks after the last study intervention administration.
A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) the day of any dose of study intervention
For adolescents: A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:
• Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be pre-menarche
OR
• Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to the first study intervention administration until at least 4 weeks after the last study intervention administration
A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) the day of any dose of study intervention
- For infants: Born at full term of pregnancy (≥37 weeks) and with a birth weight ≥2.5 kg or born after a gestation period of 27 through 36 weeks and medically stable as assessed by the investigator, based on the following definition: “Medically stable” refers to the condition of premature infants who do not require significant medical support or ongoing management for debilitating disease and who have demonstrated a clinical course of sustained recovery by the time they receive the first dose of study intervention
- Informed consent form or assent form has been signed and dated by the participant (based on local regulations), and if applicable, informed consent form has been signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations) |
|
| E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply:
- Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months or since birth for infants and toddlers; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months or since birth for infants and toddlers)
- History of any Neisseria meningitidis infection, confirmed either clinically, serologically, or microbiologically
- At high risk for meningococcal infection during the trial (specifically, but not limited to, participants with persistent complement deficiency, with anatomic or functional asplenia, or participants travelling to countries with high endemic or epidemic disease)
- Individuals with active tuberculosis
- Known systemic hypersensitivity to latex or to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances
- For adults and adolescents: Self-report of thrombocytopenia, contraindicating intra-muscular (IM) vaccination *
- For infants and toddlers: Laboratory-confirmed thrombocytopenia, or known thrombocytopenia, as reported by the parent/legally acceptable representative contraindicating intramuscular vaccination
- Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination
- For infants and toddlers: History of intussusception
- Receipt of any vaccine in the 4 weeks (28 days) preceding the first trial vaccination or planned receipt of any vaccine 4 weeks before to 4 weeks after each trial vaccination or study visit with collection of blood for immunogenicity assessments, except for influenza vaccination, which may be received at least 2 weeks before or 2 weeks after any study vaccination. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines
- Previous vaccination against meningococcal B disease with either the study vaccines or another licensed or investigational vaccine (i.e., mono- or polyvalent, polysaccharide, or conjugate meningococcal vaccine containing serogroup B)
For infants and toddlers: Previous vaccination against meningococcal disease with either the study vaccines or any other licensed or investigational vaccine containing serogroups A, C, W, Y; or meningococcal serogroup B
- Receipt of immune globulins, blood or blood-derived products in the past 3 months or since birth for infants and toddlers
- Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first immunogenicity blood draw
- For infants: Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis A, measles, mumps, rubella, varicella; and Haemophilus influenzae type b, Streptococcus pneumoniae, and /or rotavirus infection or disease, and receipt of more than 1 previous dose of hepatitis B vaccine
- Participation at the time of study enrollment (or in the 4 weeks preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
- Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
- Moderate or severe acute illness/infection (according to the investigator's judgment), febrile illness (temperature ≥ 38.0°C or ≥ 100.4°F). A prospective participant should not be enrolled in the study until the condition has resolved or the febrile event has subsided
- History of Guillain-Barré syndrome
- History of any neurologic disorders, including any seizures and progressive neurologic disorders
- Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
- For adults and adolescents: Identified as an investigator or employee of the investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the investigator or employee with direct involvement in the proposed study
For infants and toddlers: Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study
- For adults and adolescents: Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1 - Number of participants with immediate adverse events (AEs) ; Unsolicited systemic AEs that occur within 30 minutes after vaccination
2 - Number of participants with solicited injection site reactions or systemic reactions ;
Adverse reactions pre-listed in the protocol and case report form (CRF)
Injection site reactions: pain, erythema and swelling (or tenderness, erythema and swelling for infants and toddlers)
Systemic reactions: fever, headache, malaise, myalgia (or fever, vomiting, crying abnormal, drowsiness, appetite lost, irritability for infants and toddlers)
3 - Number of participants with unsolicited AEs ; AEs that do not fulfill the conditions of solicited reactions
4 - Number of participants with serious adverse events (SAEs) ; SAEs reported throughout the study, including adverse events of special interest (AESI)s
5 - Number of participants with medically attended adverse events (MAAE)s ; AEs with a new onset or a worsening of a condition that prompts the participant or participant's parent/guardian to seek unplanned medical advice at a physician’s office or Emergency Department
6 - Number of participants with out-of-range biological test results ; Out-of-range biological test results occurring in the sentinel cohorts of each age group
7 - Antibody titers in the primary panel of MenB strains before primary vaccination ; Antibody titers measured by serum bactericidal assay using human complement (hSBA)
8 - Antibody titers in the primary panel of MenB strains after primary vaccination ; Antibody titers measured by hSBA |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 - Within 30 minutes after vaccination
2 - Within 7 days after vaccination
3 - Within 30 days after vaccination
4 - Up to 6 months after last vaccination
5 - Up to 6 months after last vaccination
6 - From baseline (pre-vaccination) up to Day 07 (post-vaccination)
7 - Day 01 (pre-vaccination)
8 - Day 30 (post-vaccination) |
|
| E.5.2 | Secondary end point(s) |
1 - Antibody titers in the primary panel of MenB strains after each vaccination ; Antibody titers measured by hSBA
2 - Antibody titers in the secondary panel of MenB strains (stage 1 and 2 only) ; Antibody titers measured by hSBA
3 - Antibody titers in the primary panel of MenB strains (stage 2 only) ; Antibody titers measured by hSBA
4 - Antibody titers against each of Men A, C, W, and Y strains ; Antibody titers measured by hSBA in participants receiving MenQuadfi vaccine |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 - Day 01, Day 31, Day 61, Day 91, Day 181, Day 211, Day 366 and Day 396
2 - Day 01 (pre-vaccination) and Day 30 (post-vaccination)
3 - Day 366 (pre-vaccination) and Day 396 (post-vaccination)
4 - Day 01 (pre-vaccination) and Day 30 (post-vaccination) |
|
| 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 | Yes |
| 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) | 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 | Yes |
| 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 |
| Sequential, stages 1-2 in US and stages 2 to 4 in EU. open label in stages 3 and 4 |
|
| 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 | 8 |
| 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 | No |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
| 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 contact of the last participant in the study, i.e., Stage 4 - Month 18 safety follow-up telephone call (approximately 6 months after last vaccination) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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