Clinical trial NCT03537508: Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the US
Official title: A Phase III, Partially Modified Double-blind, Randomized, Parallel-group, Active-controlled, Multi-center Study to Compare the Immunogenicity and Describe the Safety of MenACYW Conjugate Vaccine and MENVEO® When Administered Concomitantly With Routine Pediatric Vaccines to Healthy Infants and Toddlers in the United States
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Healthy Volunteers (Meningococcal Infection)
Keywords: Meningococcal meningitis
MenACYW conjugate vaccine
Quadrivalent meningococcal vaccine
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2018-05-25
Enrollment: 2627
Sex: ALL
Minimum age (years): 42
Maximum age (years): 89
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

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 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.

Primary outcomes:
measure: 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
timeFrame: Day 30 post 12-month vaccination (Month 13)
measure: Groups 1 and 2: Percentage of Participants Who Achieved Antibody Titers >=1:8 by hSBA at Day 30 Post 6-Month Vaccination
timeFrame: Day 30 post 6-month vaccination (Month 7)
Secondary outcomes:
measure: 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
timeFrame: Day 30 post 6-month vaccination (Month 7)
measure: 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
timeFrame: Day 30 post 6-month vaccination (Month 7)
measure: Groups 1 and 2: Percentage of Participants Who Achieved Anti-Poliovirus Antibody Titers >=1:8 at Day 30 Post 6-Month Vaccination
timeFrame: Day 30 post 6-month vaccination (Month 7)
measure: 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
timeFrame: Day 30 post 6-month vaccination (Month 7)
measure: Groups 1 and 2: Geometric Mean Concentrations (GMCs) of Anti-Rotavirus IgA Antibodies at Day 30 Post 6-Month Vaccination
timeFrame: Day 30 post 6-month vaccination (Month 7)
measure: Groups 1 and 2: GMCs of Anti-Pertussis Antibodies at Day 30 Post 6-Month Vaccination
timeFrame: Day 30 post 6-month vaccination (Month 7)
measure: Groups 1 and 2: GMCs of Anti-Pneumococcal Antibodies at Day 30 Post 6-Month Vaccination
timeFrame: Day 30 post 6-month vaccination (Month 7)
measure: 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
timeFrame: Day 30 post 12-month vaccination (Month 13)
measure: Groups 1a and 2a: Percentage of Participants Who Achieved Vaccine Response for Varicella Antibodies at Day 30 Post 12-Month Vaccination
timeFrame: Day 30 post 12-month vaccination (Month 13)
measure: Groups 1a and 2a: GMCs of Anti-Pneumococcal Antibodies at Day 30 Post 12-Month Vaccination
timeFrame: Day 30 post 12-month vaccination (Month 13)
measure: Groups 1b and 2b: Percentage of Participants Who Achieved Anti-PRP Antibody Concentrations >=1.0 mcg/mL at Day 30 Post 15-Month Vaccination
timeFrame: Day 30 post 15-month vaccination (Month 16)
measure: Groups 1b and 2b: Percentage of Participants Who Achieved Anti-Poliovirus Antibody Titers >=1:8 at Day 30 Post 15-Month Vaccination
timeFrame: Day 30 post 15-month vaccination (Month 16)
measure: Groups 1b and 2b: Percentage of Participants Who Achieved Vaccine Response for Anti-Pertussis Antibodies at Day 30 Post 15-Month Vaccination
timeFrame: Day 30 post 15-month vaccination (Month 16)
measure: 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
timeFrame: Day 30 post 6-month vaccination (Month 7) and Day 0 before 12-month vaccination (Month 12)
measure: 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
timeFrame: Day 30 post 6-month vaccination (Month 7) and Day 0 before 12-month vaccination (Month 12)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Pediatric Associates Site Number : 8400026
state: Alabama
city: Dothan
country: United States
facility: Southeastern Pediatric Associates Site Number : 8400003
state: Alabama
city: Phoenix
country: United States
facility: MedPharmics, LLC - Phoenix Site Number : 8400083
state: Arizona
city: Fayetteville
country: United States
facility: Northwest Arkansas Pediatric Clinic Site Number : 8400011
state: Arkansas
city: Jonesboro
country: United States
facility: The Children's Clinic of Jonesboro, PA Site Number : 8400032
state: Arkansas
city: Anaheim
country: United States
facility: Emmaus Research Center, Inc Site Number : 8400031
state: California
city: Downey
country: United States
facility: Premier Health Research Center Site Number : 8400007
state: California
city: Huntington Park
country: United States
facility: Joint Clinical Trials Huntington Park Site Number : 8400126
state: California
city: Huntington Park
country: United States
facility: United Clinical Research Site Number : 8400092
state: California
city: Los Angeles
country: United States
facility: Matrix Clinical Research Site Number : 8400095
state: California
city: Paramount
country: United States
facility: Center for Clinical Trials, LLC Site Number : 8400030
state: California
city: West Covina
country: United States
facility: Center for Clinical Trials of San Gabriel Site Number : 8400076
state: California
city: Brooksville
country: United States
facility: Asclepes Research Centers Site Number : 8400064
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research Site Number : 8400077
state: Florida
city: Hialeah
country: United States
facility: Next Phase Research Alliance Site Number : 8400057
state: Florida
city: Homestead
country: United States
facility: Homestead Medical Clinic, P.A. Site Number : 8400014
state: Florida
city: Homestead
country: United States
facility: Next Phase Research Alliance Site Number : 8400040
state: Florida
city: Lake Mary
country: United States
facility: Children's Research, LLC Site Number : 8400063
state: Florida
city: Loxahatchee Groves
country: United States
facility: Axcess Medical Research Site Number : 8400068
state: Florida
city: Miami
country: United States
facility: Acevedo Clinical Research Associates Site Number : 8400001
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Medical Group Pediatrics Site Number : 8400108
state: Florida
city: Palmetto Bay
country: United States
facility: IMIC Inc Site Number : 8400022
state: Florida
city: Tampa
country: United States
facility: Jedidiah Clinical Research Site Number : 8400132
state: Florida
city: Chamblee
country: United States
facility: Baybol Research Institute Site Number : 8400008
state: Georgia
city: Idaho Falls
country: United States
facility: Snake River Research, PLLC Site Number : 8400073
state: Idaho
city: Evansville
country: United States
facility: Qualmedica Research, LLC Site Number : 8400106
state: Indiana
city: Louisville
country: United States
facility: Brownsboro Park Pediatrics Site Number : 8400010
state: Kentucky
city: Louisville
country: United States
facility: All Children Pediatrics Site Number : 8400043
state: Kentucky
city: Haughton
country: United States
facility: ACC Pediatric Reasearch Site Number : 8400023
state: Louisiana
city: Metairie
country: United States
facility: Velocity Clinical Research Site Number : 8400025
state: Louisiana
city: Shreveport
country: United States
facility: LSUHSC-Shreveport Site Number : 8400120
state: Louisiana
city: Frederick
country: United States
facility: University of Maryland at The Pediatric Center of Frederick Site Number : 8400004
state: Maryland
city: Silver Spring
country: United States
facility: Virgo-Carter Pediatrics Site Number : 8400041
state: Maryland
city: Biloxi
country: United States
facility: MedPharmics Biloxi Site Number : 8400080
state: Mississippi
city: Bridgeton
country: United States
facility: Craig Spiegel, MD Site Number : 8400037
state: Missouri
city: Omaha
country: United States
facility: Creighton University Site Number : 8400039
state: Nebraska
city: New York
country: United States
facility: Tiga Pediatrics Site Number : 8400137
state: New York
city: Boone
country: United States
facility: Blue Pediatric & Adolescent Medicine Group Site Number : 8400100
state: North Carolina
city: Dayton
country: United States
facility: Ohio Pediatric Research Site Number : 8400084
state: Ohio
city: Dayton
country: United States
facility: PriMed Clinical Research Site Number : 8400002
state: Ohio
city: Gresham
country: United States
facility: Cyn3rgy Research Site Number : 8400085
state: Oregon
city: Erie
country: United States
facility: Allegheny Health and Wellness Pavilion Site Number : 8400047
state: Pennsylvania
city: Charleston
country: United States
facility: Coastal Pediatric Research Charleston Site Number : 8400005
state: South Carolina
city: Greenville
country: United States
facility: Tribe Clinical Research Site Number : 8400110
state: South Carolina
city: Simpsonville
country: United States
facility: Parkside Pediatrics - Simpsonville Site Number : 8400113
state: South Carolina
city: Tullahoma
country: United States
facility: Pediatric Clinical Trials Tullahoma Site Number : 8400033
state: Tennessee
city: Austin
country: United States
facility: ARC Clinical Research at Wilson Parke Site Number : 8400059
state: Texas
city: Dallas
country: United States
facility: Oak Cliff Research Company, LLC Site Number : 8400065
state: Texas
city: Fort Worth
country: United States
facility: Helios Clinical research Site Number : 8400075
state: Texas
city: Fort Worth
country: United States
facility: University of North Texas Site Number : 8400079
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Board Site Number : 8400067
state: Texas
city: Houston
country: United States
facility: Helios Clinical Research Site Number : 8400109
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network - 7080 Southwest Fwy Site Number : 8400114
state: Texas
city: Lampasas
country: United States
facility: FMC SCIENCE Site Number : 8400053
state: Texas
city: San Antonio
country: United States
facility: Tekton Research, Inc Site Number : 8400049
state: Texas
city: San Antonio
country: United States
facility: Tekton Research Site Number : 8400128
state: Texas
city: Clinton
country: United States
facility: Ericksen Research and Development Site Number : 8400016
state: Utah
city: Kaysville
country: United States
facility: Wee Care Pediatrics Site Number : 8400035
state: Utah
city: Layton
country: United States
facility: Tanner Clinic Site Number : 8400018
state: Utah
city: Provo
country: United States
facility: Pediatric Care Site Number : 8400056
state: Utah
city: Roy
country: United States
facility: Wee Care Pediatrics Roy Site Number : 8400029
state: Utah
city: South Jordan
country: United States
facility: Copperview Medical Center Site Number : 8400038
state: Utah
city: Syracuse
country: United States
facility: Wee Care Pediatrics Syracuse Site Number : 8400024
state: Utah
city: Syracuse
country: United States
facility: Alliance for Multispecialty Research Syracuse Site Number : 8400036
state: Utah
city: Huntington
country: United States
facility: Marshall Health Site Number : 8400062
state: West Virginia
city: Caguas
country: Puerto Rico
facility: Investigational Site Number : 6300116
city: Guayama
country: Puerto Rico
facility: Investigational Site Number : 6300122
city: San Juan
country: Puerto Rico
facility: Investigational Site Number : 6300015
city: San Juan
country: Puerto Rico
facility: Investigational Site Number : 6300117
city: San Juan
country: Puerto Rico
facility: Investigational Site Number : 6300140
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Medical Director
role: STUDY_DIRECTOR
References: