Healthy Volunteers, Meningococcal Immunisation
Conditions
Brief summary
Primary Objective: * 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) 1. To describe the safety profile of the SP MenB vaccine formulations, Bexsero Vaccine and Trumenba Vaccine in healthy adults, and adolescents; 2. To describe the safety profile of the SP MenB vaccine formulations and Bexsero Vaccine in toddlers and infants; 3. To describe the safety profile of the SP MenB vaccine formulations, * when administered alone * when administered with MenQuadfiTM (MenACYW conjugate vaccine) * when administered with routine infant immunizations * 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 Secondary Objective: * 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 as measured by hSBA in the primary panel of MenB strains by Stage by age group and by vaccine schedule * To describe the immune response (breadth of coverage) in the secondary panel of MenB strains in participants (adults and adolescents) in Stage 1 and 2 after the last dose of the primary series in each group * 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
Detailed description
Study duration per participant will be approximately: 7 months for Stage 1 participants, 12 to 18.5 months for Stage 2 participants, 12 months for Stage 3 participants and 18 months for Stage 4 participants In each vaccine group at each age group (Stage 1, 3 and 4 only), the first 5 participants enrolled (sentinels) will be assessed via early safety data review (ESDR) as a cohort for the evaluation of biological safety and overall safety profile for D01-D08 post dose 1. The safety data collected will be reviewed before proceeding with recruitment of remaining participants in each study group. Enrollment of remaining participants randomized to each group will be based on the outcome of the safety assessments of the sentinels: only a positive review outcome will allow the enrollment of the sentinel cohort of the respective lower age group.
Interventions
DRUGMulticomponent Meningococcal B Vaccine
Pharmaceutical form:Liquid suspension for injection in a single vial Four liquid suspensions and one diluent (only for Stage 1) Route of administration: Intramuscular
DRUGMeningococcal Group B Vaccine MenB
Pharmaceutical form:Liquid suspension for injection in a pre-filled syringe Route of administration: Intramuscular
DRUGMeningococcal Group B Vaccine (recombinant deoxyribonucleic acid [rDNA], component, adsorbed)
Pharmaceutical form:Liquid suspension for injection in a pre-filled syringe Route of administration: Intramuscular
DRUGPlacebo
Pharmaceutical form:Liquid solution for injection in a vial Route of administration: Intramuscular
Pharmaceutical form:Liquid solution for injection in a vial Route of administration: Intramuscular
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Stage 1 and Stage 2 (adults and adolescents) will be modified double-blind: the investigators and study staff who conduct the safety assessment and the participant will not know which vaccine is administered. Only the study staff who prepare and administer the vaccine and are not involved with the safety evaluation will know which vaccine is administered. The individual(s) responsible for the preparation / administration of the vaccines will not be authorized to collect any safety or serology data. Testing laboratories will be blinded. In order to maintain the blind in Stage 2 (adults and adolescents), a placebo injection will be used. After the 6-months safety assessment from the last dose of primary vaccination, Stage 2 will be unblinded for the administration of booster vaccinations. Stage 3 and Stage 4 (toddlers and infants) will be open-label.
Intervention model description
The study will be conducted in 4 stages, sequentially: * Stage 1: adults and adolescents from the US, equally randomized to 8 vaccine groups * Stage 2; adults and adolescents from the EU and the US, equally randomized to 11 vaccine groups * Stage 3: toddlers from the EU, equally randomized to 6 vaccine groups * Stage 4: infants from the EU, equally randomized to 6 vaccine groups
Eligibility
Sex/Gender
ALL
Age
42 Days to 50 Years
Healthy volunteers
Yes
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 - - -
Exclusion criteria
-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 The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Antibody titers in the primary panel of MenB strains after primary vaccination | Day 30 (post-vaccination) | Antibody titers measured by hSBA |
| Number of participants with serious adverse events (SAEs) | Up to 6 months after last vaccination | SAEs reported throughout the study, including adverse events of special interest (AESI)s |
| Number of participants with medically attended adverse events (MAAE)s | Up to 6 months after last vaccination | 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 |
| Number of participants with out-of-range biological test results | From baseline (pre-vaccination) up to Day 07 (post-vaccination) | Out-of-range biological test results occurring in the sentinel cohorts of each age group |
| Antibody titers in the primary panel of MenB strains before primary vaccination | Day 01 (pre-vaccination) | Antibody titers measured by serum bactericidal assay using human complement (hSBA) |
| Number of participants with immediate adverse events (AEs) | Within 30 minutes after vaccination | Unsolicited systemic AEs that occur within 30 minutes after vaccination |
| Number of participants with solicited injection site reactions or systemic reactions | Within 7 days after vaccination | 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) |
| Number of participants with unsolicited AEs | Within 30 days after vaccination | AEs that do not fulfill the conditions of solicited reactions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antibody titers in the secondary panel of MenB strains (stage 1 and 2 only) | Day 01 (pre-vaccination) and Day 30 (post-vaccination) | Antibody titers measured by hSBA |
| Antibody titers in the primary panel of MenB strains (stage 2 only) | Day 366 (pre-vaccination) and Day 396 (post-vaccination) | Antibody titers measured by hSBA |
| Antibody titers against each of Men A, C, W, and Y strains | Day 01 (pre-vaccination) and Day 30 (post-vaccination) | Antibody titers measured by hSBA in participants receiving MenQuadfi vaccine |
| Antibody titers in the primary panel of MenB strains after each vaccination | Day 01, Day 31, Day 61, Day 91, Day 181, Day 211, Day 366 and Day 396 | Antibody titers measured by hSBA |
Countries
Puerto Rico, United States
Outcome results
None listed