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 | Crick

Eligibility

Sex: ALLMin age: 42 DaysMax age: 89 DaysHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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).

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

Secondary Outcomes

Groups 1 and 2: Percentage of Participants Who Achieved Antibody Titers >=1:8 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 hSBA. Percentages are rounded off to the tenth decimal place.

Time frame: At 30 days post Dose 2 (4 MoA)

Groups 3 and 4: 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 hSBA.

Time frame: 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

Functional meningococcal antibody activity against serogroups A, C, W, and Y were measured in a serum bactericidal assay utilizing the hSBA. Percentages are rounded off to the tenth decimal place.

Time frame: 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

Functional meningococcal antibody activity against serogroups A, C, W, and Y were measured in a serum bactericidal assay utilizing the hSBA. Percentages are rounded off to the tenth decimal place.

Groups 1 and 2: Percentage of Participants With Vaccine Seroresponse

Functional meningococcal antibody activity against serogroups A, C, W, and Y were measured in a serum bactericidal assay utilizing the hSBA. hSBA vaccine seroresponse was defined for a participant with a pre vaccination titer \<1:8, the post-vaccination titer must be \>=1:16 and for a participant with a pre vaccination titer \>=1:8, the post-vaccination titer must be at least 4-fold greater than the pre vaccination titer. Percentages are rounded off to the tenth decimal place.

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

Groups 3 and 4: Percentage of Participants With Vaccine Seroresponse

Time frame: 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)

Geometric Mean Concentrations (GMCs) of Anti-Pertussis Antibodies

GMCs of anti-pertussis antibodies (pertussis toxin \[PT\], filamentous hemagglutinin \[FHA\]) were measured by electrochemiluminescent (ECL) assay.

Time frame: Groups 1, 2 and 3: Day 0 before Dose 1 (2 MoA); Group 4: Day 0 before Dose 4 (12 to 18 MoA)

Geometric Mean Concentrations (GMCs) of Hexavalent Vaccines

GMCs of hexavalent vaccines were measured as: anti-diphtheria, anti-tetanus, anti-pertussis antibodies (PT, FHA) by ECL assay, anti-hepatitis antibodies (anti-Hepatitis B surface antigen \[HBsAg\]) by the commercially available VITROS ECi/ECiQ, anti-poliovirus types 1, 2, and 3 by neutralization assay and anti-Haemophilus influenzae type b (anti-polyribosylribitol phosphate \[PRP\]) by Farr-type radioimmunoassay (RIA).

Time frame: 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)

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)

GMCs of anti-diphtheria, anti-tetanus, anti-poliovirus types 1, 2, and 3, anti-haemophilus influenzae type b (anti-PRP) vaccines were measured as: anti-diphtheria, anti-tetanus by ECL assay, anti-poliovirus types 1, 2, and 3 by neutralization assay and anti-Haemophilus influenzae type b (anti-PRP) by Farr-type RIA. Response rate was defined as percentage of participants who achieved: anti diphtheria and anti-tetanus antibody concentrations \>=0.01 international units (IU)/milliliter (mL), \>=0.1 IU/mL and \>=1.0 IU/mL; anti-poliovirus types 1, 2, and 3 antibody titers \>=1:8; anti-PRP antibody concentrations \>=0.15 microgram (mcg)/mL and \>=1 mcg/mL. Percentages are rounded off to the tenth decimal place.

Time frame: 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)

Percentage of Participants Who Achieved Vaccine Seroresponse for Anti-Pertussis Antibodies

GMCs of anti-pertussis antibodies (PT, FHA) were measured by ECL assay. The pertussis vaccine seroresponse for anti-PT and anti-FHA was defined as: For groups 1, 2, and 3, 30 days after dose 2 in infancy as if the pre-primary vaccination concentration is \<4 × lower limit of quantification (LLOQ), post-primary vaccination concentration \>=4 × LLOQ, if the pre-primary vaccination concentration is \>=4 ×LLOQ, post-primary vaccination concentration \>=pre-primary vaccination concentration; and for Groups 1, 2, and 3, before and 30 days after the dose 3 and for group 4, before and 30 days after the dose 4 as if the pre-booster vaccination concentration is \<4 × LLOQ, post-booster vaccination concentration \>=4 × pre-booster concentration, if the pre-booster vaccination concentration is \>=4 × LLOQ, post-booster vaccination concentration \>=2 × pre-booster concentration. Percentages are rounded off to the tenth decimal place.

Time frame: 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)

Percentage of Participants Who Achieved Anti-Hepatitis B Antibody Concentrations >=10 and >=100 Milli-International Units (mIU)/mL

GMCs of anti-hepatitis antibodies (anti-HBsAg) was measured by the commercially available VITROS ECi/ECiQ. Response rate for anti-HBsAg was defined as percentage of participants who achieved anti-HBsAg antibody concentrations \>=10 mIU/mL and \>=100 mIU/mL. Percentages are rounded off to the tenth decimal place.

Time frame: 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)

Groups 1 and 2: Geometric Mean Concentrations (GMCs) of Pneumococcal Conjugate Vaccine (10-Valent, Adsorbed) (PCV10) Vaccine

GMCs of anti-pneumococcal antibodies was assessed by pneumococcal capsular polysaccharide (PnPS) Immunoglobulin G (IgG) ECL assay which was used to quantitate the amount of anti-streptococcus pneumoniae PS (serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F) antibodies in human serum.

Time frame: At 30 days post Dose 2 (4 MoA) and Dose 3 (12 to 18 MoA)

Groups 3 and 4: Geometric Mean Concentrations (GMCs) of Pneumococcal Conjugate Vaccine (13-Valent, Adsorbed) (PCV13) Vaccine

GMCs of anti-pneumococcal antibodies was assessed by PnPS IgG ECL assay which was used to quantitate the amount of anti-streptococcus pneumoniae PS (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) antibodies in human serum.

Time frame: 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)

Groups 1 and 2: Percentage of Participants With Response Rate >=0.35 mcg/mL for Pneumococcal Conjugate Vaccine (10-Valent, Adsorbed) PCV10 Vaccine

GMCs of anti-pneumococcal antibodies was assessed by PnPS IgG ECL assay which was used to quantitate the amount of anti-streptococcus pneumoniae PS (serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F) antibodies in human serum. Percentages are rounded off to the tenth decimal place.

Time frame: At 30 days post Dose 2 (4 MoA) and Dose 3 (12 to 18 MoA)

Groups 3 and 4: Percentage of Participants With Response Rate >=0.35 mcg/mL for Pneumococcal Conjugate Vaccine (13-Valent, Adsorbed) PCV13 Vaccine

Time frame: 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)

Geometric Mean Concentrations (GMCs) of Anti-Measles, Mumps and Rubella (MMR) Antibodies

GMCs of anti-measles and anti-rubella antibodies were measured by bulk IgG enzyme immunoassay (EIA) and anti-mumps antibodies were assessed by enzyme-linked immunosorbent assay (ELISA).

Time frame: 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)

Percentage of Participants Who Achieved Vaccine Response for Measles, Mumps and Rubella (MMR) Antibodies

GMCs of anti-measles and anti-rubella antibodies were measured by bulk IgG EIA and anti-mumps antibodies were assessed by ELISA. Vaccine response against anti-measles, anti-mumps, anti-rubella antibodies were defined as percentage of participants with anti-measles, anti-mumps, anti-rubella antibody concentration that met the respective mentioned criterion: measles: \>=255 mIU/mL; mumps: \>=10 mumps antibody units/mL and rubella: \>=10 IU/mL. Percentages are rounded off to the tenth decimal place.

Time frame: 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)

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

Overview

Conditions

Interventions

Eligibility

Locations (33)

Outcomes

Primary Outcomes

Secondary Outcomes