Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the US

Sanofi Pasteur, a Sanofi Company2,627 enrolled

Overview

The purpose of this study was to compare the immunogenicity and describe the safety of MenACYW conjugate vaccine and MENVEO® when both are administered concomitantly with routine pediatric vaccines to healthy infants and toddlers in the US.

The duration of each subject's participation in the trial was approximately 16 to 19 months (Subgroup 1a) and 19 to 22 months (Subgroup 1b and Group 2), which included a safety follow up contact at 6 months after the last vaccinations.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

2,627

Conditions

Healthy Volunteers (Meningococcal Infection)

Interventions

MenACYW conjugate vaccineBIOLOGICAL

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

MenACYW-135 conjugate vaccineBIOLOGICAL

Meningococcal (Groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine, 0.5 mL, intramuscular

DTaP-IPV//Hib vaccineBIOLOGICAL

DTaP-IPV//Hib vaccine at 2, 4, 6 and 12 to 15 (Group 1a)/15-18 (Group 1b and Group 2) months of age Intramuscular

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 guardian, and an independent witness, if required by local regulations * Participant and parent/guardian were able to attend all scheduled visits and to comply with all trial procedures. * Infants who received the first dose of hepatitis B vaccine at least 28 days before the first study visit Exclusion Criteria: * Participation at the time of study enrollment or in the 4 weeks preceding the first trial vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure * Receipt of any vaccine in the 4 weeks preceding the first trial vaccination or planned receipt of any vaccine in the 4 weeks before and/or following any trial vaccination except for influenza vaccination, which could have been received at a gap of at least 2 weeks before or 2 weeks after any study vaccination. This exception included monovalent pandemic influenza vaccines and multivalent influenza vaccines * Previous vaccination against meningococcal disease with either the trial vaccine or another vaccine (i.e., mono- or polyvalent, PS, or conjugate meningococcal vaccine containing serogroups A, C, Y, or W; or meningococcal B serogroup-containing vaccine). * Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis A, measles, mumps, rubella, varicella; and of Haemophilus influenzae type b, Streptococcus pneumoniae, and /or rotavirus infection or disease * Receipt of more than 1 previous dose of hepatitis B vaccine * 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, until 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 any Neisseria meningitidis infection, confirmed either clinically, serologically, or microbiologically * History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, hepatitis A, measles, mumps, rubella, varicella; and of Haemophilus influenzae type b, Streptococcus pneumoniae, and /or rotavirus infection or disease * At high risk for meningococcal infection during the trial (specifically, but not limited to, subjects with persistent complement deficiency, with anatomic or functional asplenia, or subjects travelling to countries with high endemic or epidemic disease) * History of intussusception * History of any neurologic disorders, including any seizures and progressive neurologic disorders * History of Guillain-Barré syndrome * Known systemic hypersensitivity to any of the vaccine components or to latex, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances, including neomycin, gelatin, and yeast * 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 * Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw * 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, was at a stage where it might have interfered with trial conduct or completion * Any condition which, in the opinion of the investigator, might have interfered with the evaluation of the study objectives * Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C \[≥ 100.4°F\]). A prospective participant was not included in the study until the condition has been resolved or the febrile event has been subsided * Identified as a natural or adopted child of the investigator or employee with direct involvement in the proposed study * The above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Locations (70)

Outcomes

Primary Outcomes

Groups 1a and 2a: Percentage of Participants With Vaccine Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) at Day 30 Post 12-Month Vaccination

Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA. Vaccine seroresponse was defined as a post 4th dose (Day 30 after 12-month) hSBA titer \>=1:16 for participants with pre 1st dose (Day 0 before 2-month) hSBA titer less than (\<) 1:8, or at least a 4-fold increase in hSBA titer from pre-vaccination to post-vaccination for participants with pre-vaccination hSBA titer \>=1:8. Percentages are rounded off to the tenth decimal place.

Time frame: Day 30 post 12-month vaccination (Month 13)

Groups 1 and 2: Percentage of Participants Who Achieved Antibody Titers >=1:8 by hSBA at Day 30 Post 6-Month Vaccination

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

Time frame: Day 30 post 6-month vaccination (Month 7)

Secondary Outcomes

Groups 1 and 2: Percentage of Participants Who Achieved Anti-Hepatitis B Antibody Concentrations >=10 Milli-International Units Per Milliliter (mIU/mL) at Day 30 Post 6-Month Vaccination

Anti-Hepatitis B surface antibodies (HBsAg) were measured by the commercially available VITROS ECi/ECiQ immunodiagnostic system using chemiluminescence detection technology. The percentage of participants with an anti-HBsAg antibody titer \>=10 mIU/mL was assessed. Percentages are rounded off to the tenth decimal place.

Time frame: Day 30 post 6-month vaccination (Month 7)

Groups 1 and 2: Percentage of Participants Who Achieved Anti-Polyribosyl-Ribitol (PRP) Antibody Concentrations >=0.15 and >=1.0 Microgram (mcg)/mL at Day 30 Post 6-Month Vaccination

Anti-PRP concentrations were measured using a farr-type radioimmunoassay (RIA). The percentage of participants with an PRP antibody titer \>=0.15 mcg/mL and \>=1.0 mcg/mL were assessed. Percentages are rounded off to the tenth decimal place.

Data from ClinicalTrials.gov

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Pneumococcal vaccine at 2, 4, 6, and 12 months of age, Intramuscular

Pentavalent rotavirus vaccineBIOLOGICAL

Rotavirus vaccine at 2, 4, and 6 months of age, oral solution

Hepatitis B vaccineBIOLOGICAL

Hepatitis B vaccine at 2 and 6 months of age, Intramuscular

Measles, mumps, rubella (MMR) vaccineBIOLOGICAL

MMR vaccine at 12 months of age, Subcutaneous

Varicella vaccineBIOLOGICAL

Varicella vaccine at 12 months of age

Hepatitis A vaccineBIOLOGICAL

Hepatitis A vaccine at 15 to 18 months of age

Birmingham Pediatric Associates Site Number : 8400026

Birmingham, Alabama, United States

Southeastern Pediatric Associates Site Number : 8400003

Dothan, Alabama, United States

MedPharmics, LLC - Phoenix Site Number : 8400083

Phoenix, Arizona, United States

Northwest Arkansas Pediatric Clinic Site Number : 8400011

Fayetteville, Arkansas, United States

The Children's Clinic of Jonesboro, PA Site Number : 8400032

Jonesboro, Arkansas, United States

Emmaus Research Center, Inc Site Number : 8400031

Anaheim, California, United States

Premier Health Research Center Site Number : 8400007

Downey, California, United States

Joint Clinical Trials Huntington Park Site Number : 8400126

Huntington Park, California, United States

United Clinical Research Site Number : 8400092

Huntington Park, California, United States

Matrix Clinical Research Site Number : 8400095

Los Angeles, California, United States

...and 60 more locations

Time frame: Day 30 post 6-month vaccination (Month 7)

Groups 1 and 2: Percentage of Participants Who Achieved Anti-Poliovirus Antibody Titers >=1:8 at Day 30 Post 6-Month Vaccination

Anti-poliovirus types 1, 2, and 3 were measured by neutralization assay. The percentage of participants with anti-polio antibody titers \>=1:8 were assessed.

Time frame: Day 30 post 6-month vaccination (Month 7)

Groups 1 and 2: Percentage of Participants Who Achieved Anti-Rotavirus Immunoglobulin A (IgA) Antibody Concentrations >=3-Fold Rise at Day 30 Post 6-Month Vaccination

Anti-rotavirus IgA antibodies in human serum were measured by enzyme-linked immunosorbent assay (ELISA). The percentage of participants who achieved anti-rotavirus IgA Ab concentrations \>=3-fold rise were assessed. Percentages are rounded off to the tenth decimal place.

Time frame: Day 30 post 6-month vaccination (Month 7)

Groups 1 and 2: Geometric Mean Concentrations (GMCs) of Anti-Rotavirus IgA Antibodies at Day 30 Post 6-Month Vaccination

GMCs of anti-rotavirus serum IgA antibodies were assessed using ELISA.

Time frame: Day 30 post 6-month vaccination (Month 7)

Groups 1 and 2: GMCs of Anti-Pertussis Antibodies at Day 30 Post 6-Month Vaccination

GMCs of anti-pertussis antibodies (pertussis toxoid \[PT\], filamentous hemagglutinin adhesin \[FHA\], pertactin \[PRN\] and fimbriae types 2 and 3 \[FIM\]) were measured by electrochemiluminescent (ECL) assay.

Time frame: Day 30 post 6-month vaccination (Month 7)

Groups 1 and 2: GMCs of Anti-Pneumococcal Antibodies at Day 30 Post 6-Month Vaccination

GMCs of anti-pneumococcal antibodies was assessed by pneumococcal capsular polysaccharide (PnPS) IgG ECL assay which is 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: Day 30 post 6-month vaccination (Month 7)

Groups 1a and 2a: Percentage of Participants Who Achieved Vaccine Response for Measles, Mumps and Rubella (MMR) Antibodies at Day 30 Post 12-Month Vaccination

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

Time frame: Day 30 post 12-month vaccination (Month 13)

Groups 1a and 2a: Percentage of Participants Who Achieved Vaccine Response for Varicella Antibodies at Day 30 Post 12-Month Vaccination

Vaccine response against anti-varicella antibodies were measured by glycoprotein (gp) ELISA. Percentage of participants with anti-varicella antibody concentration \>=5 antibody (Ab) gpELISA units/mL are reported. Percentages are rounded off to the tenth decimal place.

Time frame: Day 30 post 12-month vaccination (Month 13)

Groups 1a and 2a: GMCs of Anti-Pneumococcal Antibodies at Day 30 Post 12-Month Vaccination

GMCs of anti-pneumococcal antibodies was assessed by PnPS IgG ECL assay which is 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: Day 30 post 12-month vaccination (Month 13)

Groups 1b and 2b: Percentage of Participants Who Achieved Anti-PRP Antibody Concentrations >=1.0 mcg/mL at Day 30 Post 15-Month Vaccination

Anti-PRP concentrations were measured using a farr-type RIA. The percentage of participants with an PRP antibody titers \>=1.0 mcg/mL were assessed. Percentages are rounded off to the tenth decimal place.

Time frame: Day 30 post 15-month vaccination (Month 16)

Groups 1b and 2b: Percentage of Participants Who Achieved Anti-Poliovirus Antibody Titers >=1:8 at Day 30 Post 15-Month Vaccination

Anti-poliovirus types 1, 2, and 3 were measured by neutralization assay. The percentage of participants with anti-polio antibody titers \>=1:8 are assessed.

Time frame: Day 30 post 15-month vaccination (Month 16)

Groups 1b and 2b: Percentage of Participants Who Achieved Vaccine Response for Anti-Pertussis Antibodies at Day 30 Post 15-Month Vaccination

Vaccine response was defined as: if the pre-booster (4th) vaccination concentration was \<lower limit of quantification (LLOQ), then the post-booster (4th) vaccination concentration should be \>=4 times LLOQ. The LLOQ was equal to 2.00 EU/mL. Percentages are rounded off to the tenth decimal place.

Time frame: Day 30 post 15-month vaccination (Month 16)

Groups 1a and 2a: Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Measured by hSBA at Day 30 Post 6-Month Vaccination and Day 0 Before 12-Month Vaccination

GMTs of antibody against meningococcal serogroups A, C, Y, and W were measured by hSBA. PPAS2 included participants of FAS2 (subset of all randomized participants who received \>=1 dose of the study vaccine in infancy \[at Visit 1 to 3, \< 12 months of age\] and had a valid pre-vaccination serology result at Visit 5 before the 12-month vaccinations for Subgroups 1a and 2a or at Visit 6 before the 15-month vaccinations for Subgroups 1b and 2b) with no relevant protocol deviations during infancy and for whom a pre-dose serology sample at Visit 5 for Subgroups 1a and 2a before the 12-month vaccinations or Visit 6 for Subgroups 1b and 2b before the 15-month vaccinations was not withdrawn.

Time frame: Day 30 post 6-month vaccination (Month 7) and Day 0 before 12-month vaccination (Month 12)

Groups 1a and 2a: Percentage of Participants Who Achieved Antibody Titers >=1:4 and >=1:8 Against Meningococcal Serogroups A, C, Y, and W at Day 30 Post 6-Month Vaccination and Day 0 Before 12-Month Vaccination

Antibody titers of Meningococcal Serogroups A, C, Y, and W were measured by hSBA assay. PPAS2 included participants of FAS2 with no relevant protocol deviations during infancy and for whom a pre-dose serology sample at Visit 5 for Subgroups 1a and 2a before the 12-month vaccinations or Visit 6 for Subgroups 1b and 2b before the 15-month vaccinations was not withdrawn. Percentages are rounded off to the tenth decimal place.

Time frame: Day 30 post 6-month vaccination (Month 7) and Day 0 before 12-month vaccination (Month 12)