Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine When Co-administered With Routine Pediatric Vaccines in Healthy Infants and Toddlers in Europe

Meningococcal Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03547271
• Other study ID #: MET58
• Secondary ID: U1111-1183-6653M
• Status: Completed
• Phase: Phase 3
• Start date: December 14, 2018
• Est. completion date: May 17, 2023

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary objective is 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 is 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 are:

• 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 is 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.

• 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1660
• Est. completion date: May 17, 2023
• Est. primary completion date: May 17, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 42 Days to 89 Days

Eligibility

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 are able to attend all scheduled visits and to comply with all study procedures

• Covered by health insurance according to local regulations

Exclusion Criteria:

• articipation at the time of study enrollment (or in the 4 weeks preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure

• Receipt of 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 includes monovalent pandemic influenza vaccines and multivalent influenza vaccines. This exclusion criterion does not apply to subjects in Finland, Sweden or Poland who plan to receive the licensed rotavirus vaccine concomitantly with study vaccines at study vaccination visits V1 and V2.

• Receipt 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.

• Receipt of immune globulins, blood or blood-derived products since birth

• Known or suspected congenital or acquired immunodeficiency; or receipt of 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 with blood dyscrasias, leukemia, lymphoma of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems

• Individuals with 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

• At high risk for meningococcal infection during the study (specifically, but not limited to, subjects with persistent complement deficiency, with anatomic or functional asplenia, or subjects traveling to countries with high endemic or epidemic disease)

• Individuals with 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

• Verbal report of thrombocytopenia, contraindicating intramuscular vaccination in the investigator's opinion

• Bleeding disorder, or receipt 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, is at a stage where it might interfere with study conduct or completion

• Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives, including planning 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 should not be included in the study until the condition has resolved or the febrile event has subsided.

• Receipt of 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) requiring specific immunization schedule for routine childhood vaccines and/or specific care at the time of vaccination, as per national recommendations

Related Conditions & MeSH terms

• Meningococcal Infections

Intervention

Biological:
• MenACYW conjugate vaccine
Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine, 0.5 mL, intramuscular
• Meningococcal group A, C, W-135, and Y conjugate vaccine
Meningococcal group A, C, W-135, and Y conjugate vaccine, 0.5 mL, intramuscular
• DTaP-IPV-HB-Hib vaccine
Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine
• Pneumococcal vaccine (13-valent)
Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)
• Pneumococcal vaccine (10-valent)
Pneumococcal polysaccharide conjugate vaccine (10-valent, adsorbed)
• MMR vaccine
Measles, mumps, and rubella vaccine

Locations

Country	Name	City	State
Czechia	Investigational Site Number : 2031006	Chlumec Nad Cidlinou
Czechia	Investigational Site Number : 2031013	Domazlice
Czechia	Investigational Site Number : 2031010	Jindrichuv Hradec
Czechia	Investigational Site Number : 2031012	Jindrichuv Hradec
Czechia	Investigational Site Number : 2031003	Ostrava
Czechia	Investigational Site Number : 2031008	Ostrava-hrabuvka
Czechia	Investigational Site Number : 2031005	Pardubice
Czechia	Investigational Site Number : 2031009	Pardubice
Czechia	Investigational Site Number : 2031007	Smirice
Finland	Investigational Site Number : 2462007	Espoo
Finland	Investigational Site Number : 2462003	Helsinki
Finland	Investigational Site Number : 2462004	Helsinki
Finland	Investigational Site Number : 2462001	Järvenpää
Finland	Investigational Site Number : 2462006	Kokkola
Finland	Investigational Site Number : 2462005	Oulu
Finland	Investigational Site Number : 2462002	Pori
Finland	Investigational Site Number : 2462009	Seinajoki
Finland	Investigational Site Number : 2462010	Tampere
Finland	Investigational Site Number : 2462008	Turku
Italy	Investigational Site Number : 3803002	Milano
Poland	Investigational Site Number : 6167002	Bydgoszcz	Kujawsko-pomorskie
Poland	Investigational Site Number : 6167003	Siemianowice Slaskie
Poland	Investigational Site Number : 6167006	Torun
Poland	Investigational Site Number : 6167004	Trzebnica	Dolnoslaskie
Romania	Investigational Site Number : 6424003	Brasov
Romania	Investigational Site Number : 6424001	Bucarest
Romania	Investigational Site Number : 6424002	Calarasi
Romania	Investigational Site Number : 6424006	Caracal
Spain	Investigational Site Number : 7245002	Madrid
Spain	Investigational Site Number : 7245003	Madrid
Spain	Investigational Site Number : 7245001	Santiago de Compostela
Spain	Investigational Site Number : 7245006	Sevilla
Sweden	Investigational Site Number : 7526001	Umea

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Countries where clinical trial is conducted

Czechia,  Finland,  Italy,  Poland,  Romania,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antibody titers against meningococcal serogroups A, C, Y, and W (groups 1 and 2)	Antibody titers will be measured by the serum bactericidal assay using human complement (hSBA) and expressed as geometric mean titers (GMTs)	30 days after dose 3
Secondary	Antibody titers = 1:8 against meningococcal serogroups A, C, Y, and W (groups 1 and 2)	Percentage of participants achieving antibody titers = predefined threshold of 1:8, measured by hSBA	D0, 30 days after Dose 2 and before and 30 days after the booster dose
Secondary	Antibody titers above pre-defined thresholds for meningococcal serogroups A, C, Y, and W (all groups)	Percentage of participants achieving antibody titers = predefined thresholds, measured by hSBA	D0, 30 days after Dose 2 and before and 30 days after booster Dose 3 for groups 1, 2, 3. D0, 30 days after Dose 3 and before and 30 days after booster Dose 4 for group 4
Secondary	Antibody titers against meningococcal serogroups A, C, Y, and W (all groups)	Antibody titers will be measured by hSBA and expressed as GMTs	D0, 30 days after Dose 2 and before and 30 days after booster Dose 3 for groups 1, 2, 3. D0, 30 days after Dose 3 and before and 30 days after booster Dose 4 for group 4
Secondary	Antibody concentrations against pre-defined thresholds for antigens of DTaP-IPV-HB-Hib vaccine (all groups)	Percentage of participants with antibody concentrations = established seroprotection cut-off levels for diphtheria, tetanus, polio, hepatitis B and Hib, and seroresponse rate for anti-pertussis antibodies	30 days after dose 2, 30 days after booster dose 3 (group 3), or 30 days after booster dose 4 (group 4)
Secondary	Antibody concentrations/titers against antigens of DTaP-IPV- HB-Hib vaccine (all groups)	Antibody concentrations/titers will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations/titers (GMCs/GMTs)	30 days after dose 2, 30 days after booster dose 3 (group 3), or 30 days after booster dose 4 (group 4)
Secondary	Antibody concentrations above pre-defined thresholds for antigens of 10-valent pneumococcal vaccine (groups 1 and 2)	Percentage of participants with antibody concentrations = established seroprotection cut-off levels for antigens in the pneumococcal vaccine	30 days after dose 2 and 30 days after booster dose
Secondary	Antibody concentrations against antigens of 10-valent pneumococcal vaccine (groups 1 and 2)	Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations (GMCs)	30 days after dose 2 and 30 days after booster dose
Secondary	Antibody concentrations above pre-defined thresholds for antigens of 13-valent pneumococcal vaccine (group 3 and 4)	Percentage of participants with antibody concentrations = established seroprotection cut-off levels for antigens in the pneumococcal vaccine	30 days after dose 2 and 30 days after booster dose 3 (group 3) or 30 days after booster dose 4 (group 4)
Secondary	Antibody concentrations against antigens of 13-valent pneumococcal vaccine (group 3 and 4)	Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations (GMCs)	30 days after dose 2 and 30 days after booster dose 3 (group 3) or 30 days after booster dose 4 (group 4)
Secondary	Antibody concentrations above pre-defined thresholds for antigens of MMR vaccine (all groups)	Percentage of participants with antibody concentrations = established seroprotection cut-off levels for antigens in MMR vaccine	30 days after the booster dose
Secondary	Antibody concentrations against antigens of MMR vaccine (all groups)	Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine	30 days after the booster dose