Clinical trial NCT03547271: Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine When Co-administered With Routine Pediatric Vaccines in Healthy Infants and Toddlers in Europe
Official title: Immunogenicity and Safety Study of an Investigational Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in Europe
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Meningococcal Infections
Keywords: Meningococcal meningitis
MenACYW conjugate vaccine
Quadrivalent meningococcal vaccine
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2018-06-06
Enrollment: 1660
Sex: ALL
Minimum age (years): 42
Maximum age (years): 89
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Primary objective:

This study aimed to demonstrate the non-inferiority of the antibody response against meningococcal serogroups A, C, Y, and W following the administration of a 3-dose series of MenACYW conjugate vaccine compared to a 3-dose series of a licensed meningococcal vaccine when each vaccine was given concomitantly with routine pediatric vaccines (10-valent pneumococcal vaccine and diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b \[DTaP-IPV-HB-Hib vaccine\]) to infants and toddlers 6 weeks to 18 months old

Secondary objectives:

This study aimed to demonstrate the non-inferiority of the antibody (Ab) response against meningococcal serogroups A, C, Y, and W following the administration of 2 doses in infancy of MenACYW conjugate vaccine compared to 2 doses of a licensed meningococcal vaccine when each vaccine was given concomitantly with routine pediatric vaccines (10-valent pneumococcal vaccine and DTaP-IPV-HB-Hib vaccine) to infants and toddlers 6 weeks to 18 months old.

- This study aimed to describe the Ab responses against meningococcal groups A, C, Y, and W and the antigens of the routine pediatric vaccines administered in the study.


Eligibility criteria: Inclusion Criteria:

* Aged ≥ 42 to ≤ 89 days on the day of the first study visit
* Healthy infants as determined by medical history, physical examination and judgment of the Investigator
* Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative
* Subject and parent/legally acceptable representative were able to attend all scheduled visits and to comply with all study procedures
* Covered by health insurance according to local regulations

Exclusion Criteria:

* Participated at the time of study enrollment (or in the 4 weeks preceding the first study vaccination) or planned participation during the study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
* Received any vaccine in the 4 weeks preceding the first study vaccination or planned receipt of any vaccine in the 4 weeks before and/or following any study vaccination except for influenza vaccination and rotavirus vaccination, which may be received at a gap of at least 2 weeks before or 2 weeks after any study vaccines. This exception included monovalent pandemic influenza vaccines and multivalent influenza vaccines. This exclusion criterion did not apply to subjects in Finland, Sweden or Poland who planned to receive the licensed rotavirus vaccine concomitantly with study vaccines at study vaccination visits V1 and V2.
* Received or planned to receipt during the study period vaccination against meningococcal disease with either the study vaccine or another vaccine (i.e., mono- or polyvalent, polysaccharide, or conjugate meningococcal vaccine containing serogroups A, C, Y, or W; or meningococcal B serogroup-containing vaccine)
* Previous vaccination against diphtheria, tetanus, pertussis, Haemophilus influenzae type B (Hib), poliovirus, Streptococcus pneumoniae, measles, mumps, or rubella. Previous vaccination against hepatitis B when administered to risk groups, as per local recommendation.
* Received immune globulins, blood or blood-derived products since birth
* Known or suspected congenital or acquired immunodeficiency; or received immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks) since birth
* Family history of congenital or hereditary immunodeficiency, unless the immune competence of the potential vaccine recipient is demonstrated
* Individuals that had blood dyscrasias, leukemia, lymphoma of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems
* Individuals that had active tuberculosis
* History of Neisseria meningitidis infection, confirmed either clinically, serologically, or microbiologically
* History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, measles, mumps, rubella, and of Haemophilus influenzae type b, and / or Streptococcus pneumoniae infection or disease
* Individuals that were at high risk for meningococcal infection during the study (specifically, but not limited to, subjects that had persistent complement deficiency, with anatomic or functional asplenia, or subjects traveling to countries with high endemic or epidemic disease)
* Individuals that had underlying conditions predisposing them to invasive pneumococcal disease (specifically, but not limited to, subjects with sickle cell disease or human immunodeficiency virus \[HIV\] infection)
* History of any neurologic disorders, including seizures and progressive neurologic disorders
* History of Guillain-Barré syndrome
* Known systemic hypersensitivity to any of the vaccine components, or history of a severe allergic reaction (e.g., anaphylaxis) to the vaccine(s) used in the study or to a vaccine containing any of the same substances including neomycin, streptomycin, polymyxin B, glutaraldehyde, formaldehyde, and gelatin
* Reported of thrombocytopenia, contraindicating intramuscular vaccination in the investigator's opinion
* Bleeding disorder, or received of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the investigator's opinion
* Chronic illness (including, but not limited to, cardiac disorders, congenital heart disease, chronic lung disease, renal disorders, auto-immune disorders, diabetes, psychomotor diseases, and known congenital or genetic diseases) that, in the opinion of the investigator, were at a stage where it could interfere with study conduct or completion
* Any condition which, in the opinion of the investigator, could interfere with the evaluation of the study objectives, including planned to leave the area of the study site before the end of the study
* Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C). A prospective subject could not be included in the study until the condition was resolved or the febrile event was subsided.
* Received oral or injectable antibiotic therapy within 72 hours prior to the first blood draw Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study
* Infants born preterm (by less than 37 weeks of gestation) required specific immunization schedule for routine childhood vaccines and/or specific care at the time of vaccination, as per national recommendations

Primary outcomes:
measure: Groups 1 and 2: Geometric Mean Titers (GMTs) Against Meningococcal Serogroups A, C, W, and Y
timeFrame: At 30 days post Dose 3 [12 to 18 months of age (MoA)]
Secondary outcomes:
measure: Groups 1 and 2: Percentage of Participants Who Achieved Antibody Titers >=1:8 Against Meningococcal Serogroups A, C, W, and Y
timeFrame: At 30 days post Dose 2 (4 MoA)
measure: Groups 3 and 4: Geometric Mean Titers (GMTs) Against Meningococcal Serogroups A, C, W, and Y
timeFrame: Group 3: Day 0 before Dose 1 (2 MoA) and Dose 3 (12 to 18 MoA) and Day 30 Post Dose 2 (4 MoA) and Dose 3 (12 to 18 MoA); Group 4: Day 0 before Dose 1 (2 MoA) and Dose 4 (12 to 18 MoA) and Day 30 Post Dose 3 (6 MoA) and Dose 4 (12 to 18 MoA)
measure: Groups 1 and 2: Percentage of Participants With Serum Bactericidal Assay Using Human Complement (hSBA) Antibody Titers >=1:4 and >=1:8
timeFrame: Day 0 Before Dose 1 (2 MoA) and Day 30 Post Dose 2 (4 MoA); Day 0 Before Dose 3 (12 to 18 MoA) and Day 30 Post Dose 3 (12 to 18 MoA)
measure: Groups 3 and 4: Percentage of Participants With Serum Bactericidal Assay Using Human Complement (hSBA) Antibody Titers >=1:4 and >=1:8
timeFrame: Group 3: Day 0 before Dose 1 (2 MoA) and Dose 3 (12 to 18 MoA) and Day 30 Post Dose 2 (4 MoA) and Dose 3 (12 to 18 MoA); Group 4: Day 0 before Dose 1 (2 MoA) and Dose 4 (12 to 18 MoA) and Day 30 Post Dose 3 (6 MoA) and Dose 4 (12 to 18 MoA)
measure: Groups 1 and 2: Percentage of Participants With Vaccine Seroresponse
timeFrame: Day 30 Post Doses 2 and 3 (4 MoA and 12 to 18 MoA)
measure: Groups 3 and 4: Percentage of Participants With Vaccine Seroresponse
timeFrame: Group 3: Day 30 Post Dose 2 (4 MoA), Day 30 Post Dose 3 (12 to 18 MoA); Group 4: D30 Post Dose 3 (6 MoA), Day 30 Post Dose 4 (12 to 18 MoA)
measure: Geometric Mean Concentrations (GMCs) of Anti-Pertussis Antibodies
timeFrame: Groups 1, 2 and 3: Day 0 before Dose 1 (2 MoA); Group 4: Day 0 before Dose 4 (12 to 18 MoA)
measure: Geometric Mean Concentrations (GMCs) of Hexavalent Vaccines
timeFrame: Groups 1, 2 and 3: Day 30 Post Doses 2 and 3 (4 MoA and 12 to 18 MoA); Day 0 Before Dose 3 (12 to 18 MoA); Group 4: Day 30 Post Dose 4 (12 to 18 MoA)
measure: Percentage of Participants With Response Rate for Anti-Diphtheria, Anti-Tetanus, Anti-Poliovirus Types 1, 2, and 3, Anti-Haemophilus Influenzae Type b (Anti-PRP)
timeFrame: Groups 1, 2 and 3: Day 30 Post Doses 2 and 3 (4 MoA and 12 to 18 MoA); Day 0 Before Dose 3 (12 to 18 MoA); Group 4: Day 30 Post Dose 4 (12 to 18 MoA)
measure: Percentage of Participants Who Achieved Vaccine Seroresponse for Anti-Pertussis Antibodies
timeFrame: Groups 1, 2 and 3: Day 30 Post Doses 2 and 3 (4 MoA and 12 to 18 MoA); Group 4: Day 30 Post Dose 4 (12 to 18 MoA)
measure: Percentage of Participants Who Achieved Anti-Hepatitis B Antibody Concentrations >=10 and >=100 Milli-International Units (mIU)/mL
timeFrame: Groups 1, 2 and 3: Day 30 Post Doses 2 and 3 (4 MoA and 12 to 18 MoA); Day 0 Before Dose 3 (12 to 18 MoA); Group 4: Day 30 Post Dose 4 (12 to 18 MoA)
measure: Groups 1 and 2: Geometric Mean Concentrations (GMCs) of Pneumococcal Conjugate Vaccine (10-Valent, Adsorbed) (PCV10) Vaccine
timeFrame: At 30 days post Dose 2 (4 MoA) and Dose 3 (12 to 18 MoA)
measure: Groups 3 and 4: Geometric Mean Concentrations (GMCs) of Pneumococcal Conjugate Vaccine (13-Valent, Adsorbed) (PCV13) Vaccine
timeFrame: Group 3: At 30 days post Dose 2 (4 MoA) and Dose 3 (12 to 18 MoA); Group 4: At 30 days post Dose 4 (12 to 18 MoA)
measure: Groups 1 and 2: Percentage of Participants With Response Rate >=0.35 mcg/mL for Pneumococcal Conjugate Vaccine (10-Valent, Adsorbed) PCV10 Vaccine
timeFrame: At 30 days post Dose 2 (4 MoA) and Dose 3 (12 to 18 MoA)
measure: Groups 3 and 4: Percentage of Participants With Response Rate >=0.35 mcg/mL for Pneumococcal Conjugate Vaccine (13-Valent, Adsorbed) PCV13 Vaccine
timeFrame: Group 3: At 30 days post Dose 2 (4 MoA) and Dose 3 (12 to 18 MoA); Group 4: At 30 days post Dose 4 (12 to 18 MoA)
measure: Geometric Mean Concentrations (GMCs) of Anti-Measles, Mumps and Rubella (MMR) Antibodies
timeFrame: Groups 1, 2 and 3: At 30 days post Dose 3 (12 to 18 MoA); Group 4: At 30 days post Dose 4 (12 to 18 MoA)
measure: Percentage of Participants Who Achieved Vaccine Response for Measles, Mumps and Rubella (MMR) Antibodies
timeFrame: Groups 1, 2 and 3: At 30 days post Dose 3 (12 to 18 MoA); Group 4: At 30 days post Dose 4 (12 to 18 MoA)
Other outcomes:
Locations:
city: Chlumec Nad Cidlinou
country: Czechia
facility: Investigational Site Number : 2031006
city: Domazlice
country: Czechia
facility: Investigational Site Number : 2031013
city: Jindrichuv Hradec
country: Czechia
facility: Investigational Site Number : 2031010
city: Jindrichuv Hradec
country: Czechia
facility: Investigational Site Number : 2031012
city: Ostrava-hrabuvka
country: Czechia
facility: Investigational Site Number : 2031008
city: Ostrava
country: Czechia
facility: Investigational Site Number : 2031003
city: Pardubice
country: Czechia
facility: Investigational Site Number : 2031009
city: Pardubice
country: Czechia
facility: Investigational Site Number : 2031005
city: Smirice
country: Czechia
facility: Investigational Site Number : 2031007
city: Espoo
country: Finland
facility: Investigational Site Number : 2462007
city: Helsinki
country: Finland
facility: Investigational Site Number : 2462003
city: Helsinki
country: Finland
facility: Investigational Site Number : 2462004
city: Järvenpää
country: Finland
facility: Investigational Site Number : 2462001
city: Kokkola
country: Finland
facility: Investigational Site Number : 2462006
city: Oulu
country: Finland
facility: Investigational Site Number : 2462005
city: Pori
country: Finland
facility: Investigational Site Number : 2462002
city: Seinajoki
country: Finland
facility: Investigational Site Number : 2462009
city: Tampere
country: Finland
facility: Investigational Site Number : 2462010
city: Turku
country: Finland
facility: Investigational Site Number : 2462008
city: Milano
country: Italy
facility: Investigational Site Number : 3803002
city: Trzebnica
country: Poland
facility: Investigational Site Number : 6167004
state: Dolnoslaskie
city: Bydgoszcz
country: Poland
facility: Investigational Site Number : 6167002
state: Kujawsko-pomorskie
city: Siemianowice Slaskie
country: Poland
facility: Investigational Site Number : 6167003
city: Torun
country: Poland
facility: Investigational Site Number : 6167006
city: Brasov
country: Romania
facility: Investigational Site Number : 6424003
city: Bucaresti
country: Romania
facility: Investigational Site Number : 6424001
city: Calarasi
country: Romania
facility: Investigational Site Number : 6424002
city: Caracal
country: Romania
facility: Investigational Site Number : 6424006
city: Madrid
country: Spain
facility: Investigational Site Number : 7245003
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Investigational Site Number : 7245002
city: Santiago de Compostela
country: Spain
facility: Investigational Site Number : 7245001
city: Sevilla
country: Spain
facility: Investigational Site Number : 7245006
city: Umea
country: Sweden
facility: Investigational Site Number : 7526001
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: