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

Sanofi

Status and phase: Completed; Phase 3

Conditions: Meningococcal Infections

Treatments: Biological: DTaP-IPV-HB-Hib vaccine; Biological: Pneumococcal vaccine (13-valent); Biological: Pneumococcal vaccine (10-valent); Biological: MMR vaccine; Biological: MenACYW conjugate vaccine; Biological: Meningococcal group A, C, W-135, and Y conjugate vaccine

Study type: Interventional

Funder types: Industry

Identifiers

NCT03547271

2017-004731-36 (EudraCT Number)

MET58

U1111-1183-6653 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 1,660 patients

Sex: All

Ages: 42 to 89 days old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,660 participants in 4 patient groups

Group 1: MenACYW

Experimental group

Description:

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.

Treatment:

Biological: MMR vaccine

Biological: MenACYW conjugate vaccine

Biological: Pneumococcal vaccine (10-valent)

Biological: DTaP-IPV-HB-Hib vaccine

Group 2: Nimenrix

Active Comparator group

Description:

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.

Treatment:

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

Biological: MMR vaccine

Biological: Pneumococcal vaccine (10-valent)

Biological: DTaP-IPV-HB-Hib vaccine

Group 3: MenACYW

Experimental group

Description:

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.

Treatment:

Biological: MMR vaccine

Biological: MenACYW conjugate vaccine

Biological: Pneumococcal vaccine (13-valent)

Biological: DTaP-IPV-HB-Hib vaccine

Group 4: MenACYW

Experimental group

Description:

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.

Treatment:

Biological: MMR vaccine

Biological: MenACYW conjugate vaccine

Biological: Pneumococcal vaccine (13-valent)

Biological: DTaP-IPV-HB-Hib vaccine