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

NCT03547271 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: MET58U1111-1183-66532017-004731-36
• Study Type: interventional
• Target: 1,660
• Locations: 7 countries
• Sites: 33

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

Keywords

Meningococcal meningitis; MenACYW conjugate vaccine; Quadrivalent meningococcal vaccine

Outcome Measures

Primary Outcomes (1)

• Groups 1 and 2: Geometric Mean Titers (GMTs) Against Meningococcal Serogroups A, C, W, and Y

  Functional meningococcal antibody activity against serogroups A, C, W, and Y were measured in a serum bactericidal assay utilizing the serum bactericidal assay using human complement (hSBA).

  At 30 days post Dose 3 [12 to 18 months of age (MoA)]

Secondary Outcomes (17)

• Groups 1 and 2: Percentage of Participants Who Achieved Antibody Titers >=1:8 Against Meningococcal Serogroups A, C, W, and Y

  At 30 days post Dose 2 (4 MoA)

• Groups 3 and 4: Geometric Mean Titers (GMTs) Against Meningococcal Serogroups A, C, W, and Y

  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)

• Groups 1 and 2: Percentage of Participants With Serum Bactericidal Assay Using Human Complement (hSBA) Antibody Titers >=1:4 and >=1:8

  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)

• Groups 3 and 4: Percentage of Participants With Serum Bactericidal Assay Using Human Complement (hSBA) Antibody Titers >=1:4 and >=1:8

  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)

• Groups 1 and 2: Percentage of Participants With Vaccine Seroresponse

  Day 30 Post Doses 2 and 3 (4 MoA and 12 to 18 MoA)

Study Arms (4)

Group 1: MenACYW

EXPERIMENTAL

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.

Biological: MenACYW conjugate vaccine; Biological: DTaP-IPV-HB-Hib vaccine; Biological: Pneumococcal vaccine (10-valent); Biological: MMR vaccine

Group 2: Nimenrix

ACTIVE COMPARATOR

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.

Biological: Meningococcal group A, C, W-135, and Y conjugate vaccine; Biological: DTaP-IPV-HB-Hib vaccine; Biological: Pneumococcal vaccine (10-valent); Biological: MMR vaccine

Group 3: MenACYW

EXPERIMENTAL

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.

Biological: MenACYW conjugate vaccine; Biological: DTaP-IPV-HB-Hib vaccine; Biological: Pneumococcal vaccine (13-valent); Biological: MMR vaccine

Group 4: MenACYW

EXPERIMENTAL

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.

Biological: MenACYW conjugate vaccine; Biological: DTaP-IPV-HB-Hib vaccine; Biological: Pneumococcal vaccine (13-valent); Biological: MMR vaccine

Interventions

MenACYW conjugate vaccine BIOLOGICAL

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

Also known as: MenQuadfi®

Group 1: MenACYW; Group 3: MenACYW; Group 4: MenACYW

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

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

Also known as: Nimenrix®

Group 2: Nimenrix

DTaP-IPV-HB-Hib vaccine BIOLOGICAL

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

Also known as: Hexyon®/Hexacima®

Group 1: MenACYW; Group 2: Nimenrix; Group 3: MenACYW; Group 4: MenACYW

Pneumococcal vaccine (13-valent) BIOLOGICAL

Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)

Also known as: Prevenar 13®

Group 3: MenACYW; Group 4: MenACYW

Pneumococcal vaccine (10-valent) BIOLOGICAL

Pneumococcal polysaccharide conjugate vaccine (10-valent, adsorbed)

Also known as: Synflorix®

Group 1: MenACYW; Group 2: Nimenrix

MMR vaccine BIOLOGICAL

Measles, mumps, and rubella vaccine

Also known as: M-M-RVAXPRO®

Group 1: MenACYW; Group 2: Nimenrix; Group 3: MenACYW; Group 4: MenACYW

Eligibility Criteria

• Age: 42 Days - 89 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (33)

Investigational Site Number : 2031006

Chlumec nad Cidlinou, 503 51, Czechia

Location

Investigational Site Number : 2031013

Domažlice, 34401, Czechia

Location

Investigational Site Number : 2031010

Jindřichův Hradec, 377 01, Czechia

Location

Investigational Site Number : 2031012

Jindřichův Hradec, 377 01, Czechia

Location

Investigational Site Number : 2031003

Ostrava, 702 00, Czechia

Location

Investigational Site Number : 2031008

Ostrava-hrabuvka, 700 30, Czechia

Location

Investigational Site Number : 2031009

Pardubice, 530 09, Czechia

Location

Investigational Site Number : 2031005

Pardubice, 530 12, Czechia

Location

Investigational Site Number : 2031007

Smiřice, 503 03, Czechia

Location

Investigational Site Number : 2462007

Espoo, 02230, Finland

Location

Investigational Site Number : 2462003

Helsinki, 00100, Finland

Location

Investigational Site Number : 2462004

Helsinki, 00930, Finland

Location

Investigational Site Number : 2462001

Jarvenpaa, 04400, Finland

Location

Investigational Site Number : 2462006

Kokkola, 67100, Finland

Location

Investigational Site Number : 2462005

Oulu, 90220, Finland

Location

Investigational Site Number : 2462002

Pori, 28100, Finland

Location

Investigational Site Number : 2462009

Seinäjoki, 60100, Finland

Location

Investigational Site Number : 2462010

Tampere, 33100, Finland

Location

Investigational Site Number : 2462008

Turku, 20520, Finland

Location

Investigational Site Number : 3803002

Milan, 20122, Italy

Location

Investigational Site Number : 6167002

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-090, Poland

Location

Investigational Site Number : 6167004

Trzebnica, Lower Silesian Voivodeship, 55-100, Poland

Location

Investigational Site Number : 6167003

Siemianowice Śląskie, 41-103, Poland

Location

Investigational Site Number : 6167006

Torun, 87-100, Poland

Location

Investigational Site Number : 6424003

Brasov, 500063, Romania

Location

Investigational Site Number : 6424001

Bucaresti, 21105, Romania

Location

Investigational Site Number : 6424006

Caracal, 235200, Romania

Location

Investigational Site Number : 6424002

Călăraşi, 910160, Romania

Location

Investigational Site Number : 7245003

Madrid, Madrid, Comunidad de, 28007, Spain

Location

Investigational Site Number : 7245002

Madrid, 28046, Spain

Location

Investigational Site Number : 7245001

Santiago de Compostela, 15706, Spain

Location

Investigational Site Number : 7245006

Seville, 41014, Spain

Location

Investigational Site Number : 7526001

Umeå, 901 87, Sweden

Location

Related Publications (1)

• 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.

  PMID: 40665158 DERIVED

MeSH Terms

Conditions

Meningococcal Infections; Meningitis, Meningococcal

Interventions

13-valent pneumococcal vaccine; 10-valent pneumococcal vaccine; PHiD-CV vaccine; Measles-Mumps-Rubella Vaccine

Condition Hierarchy (Ancestors)

Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Vaccines, Combined; Vaccines; Biological Products; Complex Mixtures; Measles Vaccine; Viral Vaccines; Mumps Vaccine; Rubella Vaccine

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi Pasteur

Contact-US@sanofi.com

800-633-1610 ext: 6#

Study Officials

• Clinical Sciences & Operations

  Sanofi Pasteur, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Modified double blind for Groups 1 and 2 and open label for Groups 3 and 4 for meningococcal vaccines. Open-label for all concomitant routine vaccines. Modified double-blind: the participants parent / legally acceptable representative, the Investigator, and other study personnel remain unaware of the treatment assignments throughout the trial. An unblinded vaccine administrator will administer the appropriate vaccines but will not be involved in safety data collection.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: June 6, 2018
• Study Start: December 14, 2018
• Primary Completion: May 17, 2023
• Study Completion: May 24, 2023
• Last Updated: March 3, 2025
• Results First Posted: January 22, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

FI (10); PL (4); SE (1); CZ (9); RO (4); ES (4); IT (1)