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

NCT ID: NCT03547271

Last Updated: 2025-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1660 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-14
• Study Completion Date: 2023-05-24

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.

Conditions

Meningococcal Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1: MenACYW

Participants received 3 doses of meningococcal polysaccharide (serogroups A, C, Y and W) tetanus toxoid \[MenACYW conjugate vaccine\] 0.5 milliliter (mL) as an intramuscular (IM) injection at dose 1: 2 months of age (MoA), dose 2: 4 MoA, and dose 3: 12 to 18 MoA along with routine pediatric vaccines. The routine pediatric vaccines: hexavalent vaccine (combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and haemophilus influenzae type b conjugate vaccine \[DTaP-IPV-HB-Hib\], the pneumococcal vaccine (pneumococcal conjugate vaccine \[10-valent, adsorbed\] {PCV10} were administered in a 2+1 regimen (ie, 2 doses in infancy \[first between 6 and 12 weeks of age and second between 4 to 5 MoA\] and 1 final dose in the second year of life \[12 to 18 MoA\]); and the measles, mumps, rubella (MMR) vaccine was administered at 12 to 18 MoA.

Group Type: EXPERIMENTAL

MenACYW conjugate vaccine

Intervention Type: BIOLOGICAL

Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine, 0.5 mL, intramuscular

DTaP-IPV-HB-Hib vaccine

Intervention Type: BIOLOGICAL

Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine

Pneumococcal vaccine (10-valent)

Intervention Type: BIOLOGICAL

Pneumococcal polysaccharide conjugate vaccine (10-valent, adsorbed)

MMR vaccine

Intervention Type: BIOLOGICAL

Measles, mumps, and rubella vaccine

Group 2: Nimenrix

Participants received 3 doses of Nimenrix® 0.5 mL as an IM injection at dose 1: 2 MoA, dose 2: 4 MoA, and dose 3: 12 to 18 MoA along with routine pediatric vaccines. The routine pediatric vaccines: hexavalent vaccine (DTaP-IPV-HB-Hib), the PCV10 were administered in a 2+1 regimen (ie, 2 doses in infancy \[first between 6 and 12 weeks of age and second between 4 to 5 MoA\] and 1 final dose in the second year of life \[12 to 18 MoA\]); and the MMR vaccine was administered at 12 to 18 MoA.

Group Type: ACTIVE_COMPARATOR

Meningococcal group A, C, W-135, and Y conjugate vaccine

Intervention Type: BIOLOGICAL

Meningococcal group A, C, W-135, and Y conjugate vaccine, 0.5 mL, intramuscular

DTaP-IPV-HB-Hib vaccine

Intervention Type: BIOLOGICAL

Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine

Pneumococcal vaccine (10-valent)

Intervention Type: BIOLOGICAL

Pneumococcal polysaccharide conjugate vaccine (10-valent, adsorbed)

MMR vaccine

Intervention Type: BIOLOGICAL

Measles, mumps, and rubella vaccine

Group 3: MenACYW

Participants received 3 doses of MenACYW conjugate vaccine 0.5 mL as an IM injection at dose 1: 2 MoA, dose 2: 4 MoA, and dose 3: 12 to 18 MoA along with routine pediatric vaccines. The routine pediatric vaccines: hexavalent vaccine (DTaP-IPV-HB-Hib), the pneumococcal conjugate vaccine (13-valent, adsorbed) \[PCV13\] were administered in a 2+1 regimen (ie, 2 doses in infancy \[first between 6 and 12 weeks of age and second between 4 to 5 MoA\] and 1 final dose in the second year of life \[12 to 18 MoA\]); and the MMR vaccine was administered at 12 to 18 MoA.

Group Type: EXPERIMENTAL

MenACYW conjugate vaccine

Intervention Type: BIOLOGICAL

Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine, 0.5 mL, intramuscular

DTaP-IPV-HB-Hib vaccine

Intervention Type: BIOLOGICAL

Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine

Pneumococcal vaccine (13-valent)

Intervention Type: BIOLOGICAL

Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)

MMR vaccine

Intervention Type: BIOLOGICAL

Measles, mumps, and rubella vaccine

Group 4: MenACYW

Participants received 4 doses of MenACYW conjugate vaccine 0.5 mL as an IM injection at dose 1: 2 MoA, dose 2: 4 MoA, and dose 3: 6 MoA and dose 4: 12 to 18 MoA along with routine pediatric vaccines. The routine pediatric vaccines: hexavalent vaccine (DTaP-IPV-HB-Hib), the PCV13 were administered in a 2+1 regimen (concomitantly with the first and second doses in infancy \[first between 6 and 12 weeks of age and second between 4 to 5 MoA\] and the toddler dose of MenACYW conjugate vaccine \[12 to 18 MoA\]); and the MMR vaccine was administered at 12 to 18 MoA. The third dose of MenACYW conjugate vaccine was administered alone, without any other routine pediatric vaccines.

Group Type: EXPERIMENTAL

MenACYW conjugate vaccine

Intervention Type: BIOLOGICAL

Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine, 0.5 mL, intramuscular

DTaP-IPV-HB-Hib vaccine

Intervention Type: BIOLOGICAL

Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine

Pneumococcal vaccine (13-valent)

Intervention Type: BIOLOGICAL

Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)

MMR vaccine

Intervention Type: BIOLOGICAL

Measles, mumps, and rubella vaccine

Interventions

MenACYW conjugate vaccine

Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine, 0.5 mL, intramuscular

Intervention Type: BIOLOGICAL

Meningococcal group A, C, W-135, and Y conjugate vaccine

Meningococcal group A, C, W-135, and Y conjugate vaccine, 0.5 mL, intramuscular

Intervention Type: BIOLOGICAL

DTaP-IPV-HB-Hib vaccine

Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine

Intervention Type: BIOLOGICAL

Pneumococcal vaccine (13-valent)

Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)

Intervention Type: BIOLOGICAL

Pneumococcal vaccine (10-valent)

Pneumococcal polysaccharide conjugate vaccine (10-valent, adsorbed)

Intervention Type: BIOLOGICAL

MMR vaccine

Measles, mumps, and rubella vaccine

Intervention Type: BIOLOGICAL

Other Intervention Names

MenQuadfi®; Nimenrix®; Hexyon®/Hexacima®; Prevenar 13®; Synflorix®; M-M-RVAXPRO®

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

• Minimum Eligible Age: 42 Days
• Maximum Eligible Age: 89 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Sanofi Pasteur, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi Pasteur, a Sanofi Company

Locations

Investigational Site Number : 2031006

Chlumec nad Cidlinou, , Czechia

Investigational Site Number : 2031013

Domažlice, , Czechia

Investigational Site Number : 2031010

Jindřichův Hradec, , Czechia

Investigational Site Number : 2031012

Jindřichův Hradec, , Czechia

Investigational Site Number : 2031003

Ostrava, , Czechia

Investigational Site Number : 2031008

Ostrava-hrabuvka, , Czechia

Investigational Site Number : 2031009

Pardubice, , Czechia

Investigational Site Number : 2031005

Pardubice, , Czechia

Investigational Site Number : 2031007

Smiřice, , Czechia

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

Seinäjoki, , Finland

Investigational Site Number : 2462010

Tampere, , Finland

Investigational Site Number : 2462008

Turku, , Finland

Investigational Site Number : 3803002

Milan, , Italy

Investigational Site Number : 6167002

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Investigational Site Number : 6167004

Trzebnica, Lower Silesian Voivodeship, Poland

Investigational Site Number : 6167003

Siemianowice Śląskie, , Poland

Investigational Site Number : 6167006

Torun, , Poland

Investigational Site Number : 6424003

Brasov, , Romania

Investigational Site Number : 6424001

Bucaresti, , Romania

Investigational Site Number : 6424006

Caracal, , Romania

Investigational Site Number : 6424002

Călăraşi, , Romania

Investigational Site Number : 7245003

Madrid, Madrid, Comunidad de, Spain

Investigational Site Number : 7245002

Madrid, , Spain

Investigational Site Number : 7245001

Santiago de Compostela, , Spain

Investigational Site Number : 7245006

Seville, , Spain

Investigational Site Number : 7526001

Umeå, , Sweden

Countries

Czechia; Finland; Italy; Poland; Romania; Spain; Sweden

References

Martinon-Torres F, Virta MM, Koski S, de la Cueva IS, Szymanski HT, Bosis S, Draganescu AC, Silfverdal SA, Zambrano B, Dhingra MS, B'Chir S, Syrkina O, Lyabis O, Vasquez GA, Rehm C; MET58 Study Group. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered with Routine Pediatric Vaccines: A European Randomized Controlled Trial. Infect Dis Ther. 2025 Aug;14(8):1843-1865. doi: 10.1007/s40121-025-01190-7. Epub 2025 Jul 15.

Reference Type: DERIVED

PMID: 40665158 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1183-6653

Identifier Type: REGISTRY

Identifier Source: secondary_id

MET58

Identifier Type: OTHER

Identifier Source: secondary_id

2017-004731-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MET58

Identifier Type: -

Identifier Source: org_study_id