Safety of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers (MET41)

A Randomized Study to Describe the Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers

The primary objective of this study was to describe the safety profile of Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid (MenACYW) Conjugate Vaccine and Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 (MENVEO®) Conjugate Vaccine when administered concomitantly with routine pediatric vaccines in healthy infants and toddlers.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers (Meningococcal Infection)
• Intervention / Treatment: Biological: Pneumococcal 13-valent Conjugate Vaccine; Biological: Hepatitis B Vaccine; Biological: Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid Conjugate vaccine (MenACYW Conjugate vaccine); Biological: Diphtheria, Tetanus, Acellular Pertussis, Poliovirus and Haemophilus b Vaccine; Biological: Rotavirus Vaccine; Biological: Measles, Mumps, and Rubella Virus Vaccine; Biological: Varicella Virus Vaccine; Biological: Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine (MENVEO®)

Detailed Description

Study duration per participant was approximately 16 months, which includes a safety follow-up contact at 6 months after the final vaccination.

• Study Type: Interventional
• Enrollment (Actual): 2797
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Investigational Site Number :6300014
  • San Juan, Puerto Rico, 00918
    • Investigational Site Number :6300108
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Birmingham Pediatric Associates-Site Number:8400049
    • Dothan, Alabama, United States, 36305
      • Southeastern Pediatric Associates-Site Number:8400034
  • Arizona
    • Phoenix, Arizona, United States, 85015
      • MedPharmics, LLC - Phoenix-Site Number:8400043
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Northwest Arkansas Pediatric Clinic-Site Number:8400042
    • Hot Springs, Arkansas, United States, 71913
      • HealthStar Research, LLC-Site Number:8400100
    • Jonesboro, Arkansas, United States, 72401
      • The Children's Clinic of Jonesboro, PA-Site Number:8400059
  • California
    • Anaheim, California, United States, 92804
      • Emmaus Research Center, Inc-Site Number:8400057
    • Banning, California, United States, 92220
      • Advanced Clinical Research - Rancho Paseo-Site Number:8400087
    • Downey, California, United States, 90240
      • Premier Health Research Center, LLC-Site Number:8400039
    • Paramount, California, United States, 90723
      • Center for Clinical Trials, LLC-Site Number:8400056
    • West Covina, California, United States, 91790
      • Center for Clinical Trials of San Gabriel-Site Number:8400051
    • West Covina, California, United States, 91790
      • Center for Clinical Trials of San Gabriel-Site Number:8400099
  • Colorado
    • Colorado Springs, Colorado, United States, 80922
      • Optum Clinical Research-Site Number:8400076
    • Thornton, Colorado, United States, 80233
      • IMMUNOe Research Centers - Thornton-Site Number:8400022
  • Florida
    • DeLand, Florida, United States, 32720-0834
      • Avail Clinical Research, LLC-Site Number:8400055
    • Fort Myers, Florida, United States, 33907
      • Advanced Research for Health Improvement-Site Number:8400096
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials-Site Number:8400003
    • Miami, Florida, United States, 33174
      • De Armas Research Center,-Site Number:8400088
    • Miami, Florida, United States, 33175
      • Healthy Life Research-Site Number:8400075
    • Miami, Florida, United States, 33186
      • Acevedo Clinical Research Associates-Site Number:8400032
    • Miami Lakes, Florida, United States, 33014
      • Crystal Biomedical Research-Site Number:8400018
    • Naples, Florida, United States, 8400011
      • Advanced Research for Health Improvement-Site Number:8400005
  • Georgia
    • Macon, Georgia, United States, 31210
      • Meridian Clinical Research-Site Number:8400114
  • Indiana
    • Mishawaka, Indiana, United States, 46544
      • MOC Research-Site Number:8400095
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Kentucky Pediatics / Adult Research-Site Number:8400044
    • Louisville, Kentucky, United States, 40202
      • University of Louisville-Site Number:8400082
    • Louisville, Kentucky, United States, 40207
      • Brownsboro Park Pediatrics-Site Number:8400040
    • Louisville, Kentucky, United States, 40243
      • All Children Pediatrics-Site Number:8400069
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • MedPharmics-Site Number:8400048
  • Massachusetts
    • Fall River, Massachusetts, United States, 02721
      • Pediatric Associates of Fall River-Site Number:8400103
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
      • MedPharmics Biloxi-Site Number:8400052
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • Craig Spiegel, MD-Site Number:8400067
    • Kansas City, Missouri, United States, 64114
      • Center for Pharmaceutical Research-Site Number:8400080
  • Nebraska
    • Lincoln, Nebraska, United States, 68504
      • Midwest Childrens Health Research Institute-Site Number:8400060
  • New York
    • Rochester, New York, United States, 14618
      • Legacy Pediatrics-Site Number:8400004
  • North Carolina
    • Greensboro, North Carolina, United States, 27360
      • Medication Management-Site Number:8400072
    • Winston-Salem, North Carolina, United States, 27103
      • Ford, Simpson, Lively & Rice Pediatrics-Site Number:8400021
  • Ohio
    • Dayton, Ohio, United States, 45414
      • Ohio Pediatric Research-Site Number:8400064
    • Dayton, Ohio, United States, 45419
      • PriMed Clinical Research-Site Number:8400033
    • South Euclid, Ohio, United States, 44121
      • Senders Pediatrics-Site Number:8400061
  • Oklahoma
    • Bethany, Oklahoma, United States, 73008
      • The Children's Center Rehabilitation Hospital-Site Number:8400104
    • Tulsa, Oklahoma, United States, 74127
      • Oklahoma State University - Center for Health Sciences-Site Number:8400008
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Cyn3rgy Research-Site Number:8400035
  • South Carolina
    • Barnwell, South Carolina, United States, 29812
      • Rainbow Pediatrics-Site Number:8400074
    • Charleston, South Carolina, United States, 29414
      • Coastal Pediatric Research Charleston-Site Number:8400037
    • Mount Pleasant, South Carolina, United States, 29464
      • PMG Research of Charleston, LLC-Site Number:8400102
    • North Charleston, South Carolina, United States, 29406
      • Palmetto Pediatrics, PA-Site Number:8400089
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • PMG Research-Bristol-Site Number:8400009
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group, Pediatrics at Stone Plaza-Site Number:8400015
    • Tullahoma, Tennessee, United States, 37388
      • Pediatric Clinical Trials Tullahoma-Site Number:8400062
  • Texas
    • Austin, Texas, United States, 78726
      • ARC Clinical Research at Wilson Parke-Site Number:8400071
    • Buda, Texas, United States, 78610
      • Benchmark Research - Buda-Site Number:8400016
    • Corpus Christi, Texas, United States, 78413
      • Crossroads Clinical Research-Site Number:8400058
    • San Angelo, Texas, United States, 76904
      • Benchmark Research - San Angelo-Site Number:8400011
    • San Antonio, Texas, United States, 78229
      • Southwest Children's Research Associates, P.A.-Site Number:8400002
  • Utah
    • Clinton, Utah, United States, 84015
      • Tanner Clinic-Site Number:8400079
    • Kaysville, Utah, United States, 84037
      • Wee Care Pediatrics-Site Number:8400065
    • Murray, Utah, United States, 84107
      • Murray Pediatrics-Site Number:8400019
    • Orem, Utah, United States, 84057
      • Utah Valley Pediatrics - Timpanogos-Site Number:8400038
    • Provo, Utah, United States, 84064
      • Pediatric Care-Site Number:8400045
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research-Site Number:8400053
    • Salt Lake City, Utah, United States, 84121
      • Foothill Family Research-South-Site Number:8400036
    • South Jordan, Utah, United States, 84095
      • Copperview Medical Center-Site Number:8400068
    • South Jordan, Utah, United States, 84095
      • J Lewis Research Inc-Site Number:8400050
    • Syracuse, Utah, United States, 84075-9645
      • Alliance for Multispecialty Research Syracuse-Site Number:8400066
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • Pediatric Medical Research of Charlottesville-Site Number:8400077
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449-5777
      • Marshfield Clinic-Site Number:8400054

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: Yes

Description

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 was signed and dated by the parent(s) or guardian (and by an independent witness if required by local regulations).
• Participant and parent/guardian were able to attend all scheduled visits and complied 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 might be received at least 2 weeks before or 2 weeks after any study vaccination. This exception includes 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, polysaccharide, 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 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 was 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, Haemophilus influenzae type b, Streptococcus pneumoniae, and /or rotavirus infection/disease.
• At high risk for meningococcal infection during the trial (specifically, but not limited to, participants with persistent complement deficiency, with anatomic or functional asplenia, or participants traveling to countries with high endemic or epidemic disease).
• History of intussusception.
• 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 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.
• 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, is at a stage where it might interfere with trial conduct or completion.
• Any condition which, in the opinion of the Investigator, might interfere 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 degree Celsius [>= 100.4-degree Fahrenheit]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has 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 participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: MenACYW Conjugate Vaccine; Healthy infants aged greater than equal to (>=) 42 to less than equal to (<=) 89 days (at the time of enrollment) received MenACYW Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (pneumococcal 13-valent conjugate vaccine; PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.	Biological: Pneumococcal 13-valent Conjugate Vaccine; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular; Biological: Hepatitis B Vaccine; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular; Biological: Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid Conjugate vaccine (MenACYW Conjugate vaccine); Pharmaceutical form: Liquid solution. Route of administration: Intramuscular; Biological: Diphtheria, Tetanus, Acellular Pertussis, Poliovirus and Haemophilus b Vaccine; Pharmaceutical form: Liquid DTaP-IPV to reconstitute lyophilized ActHIB Route of administration: Intramuscular; Biological: Rotavirus Vaccine; Pharmaceutical form: Oral solution Route of administration: Oral; Biological: Measles, Mumps, and Rubella Virus Vaccine; Pharmaceutical form: Lyophilized live virus vaccine Route of administration: Subcutaneous; Biological: Varicella Virus Vaccine; Pharmaceutical form: Suspension for injection Route of administration: Subcutaneous
Active Comparator: Group 2: MENVEO®; Healthy infants aged >= 42 to <= 89 days (at the time of enrollment) received MENVEO® Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.	Biological: Pneumococcal 13-valent Conjugate Vaccine; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular; Biological: Hepatitis B Vaccine; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular; Biological: Diphtheria, Tetanus, Acellular Pertussis, Poliovirus and Haemophilus b Vaccine; Pharmaceutical form: Liquid DTaP-IPV to reconstitute lyophilized ActHIB Route of administration: Intramuscular; Biological: Rotavirus Vaccine; Pharmaceutical form: Oral solution Route of administration: Oral; Biological: Measles, Mumps, and Rubella Virus Vaccine; Pharmaceutical form: Lyophilized live virus vaccine Route of administration: Subcutaneous; Biological: Varicella Virus Vaccine; Pharmaceutical form: Suspension for injection Route of administration: Subcutaneous; Biological: Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine (MENVEO®); Pharmaceutical form: Lyophilized powder combined with liquid components Route of administration: Intramuscular

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs)	An AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which did not have any causal relationship with the treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. Immediate adverse events are unsolicited systemic adverse events occurring in the 30 minutes after injection. Reported AEs for each arm were presented as pre-specified in protocol.	Within 30 minutes post-any vaccination
Number of Participants With Solicited Injection Site Reactions	A solicited reaction was an "expected" adverse reaction (AR) (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRB and considered as related to the product administered. Solicited injection site reactions included Injection site tenderness, Injection site erythema, and Injection site swelling and were planned to be collected and reported for each vaccine separately; and not planned to be collected for Rotavirus vaccine as the vaccine was administered orally, and no injection site reactions were expected to occur. Reported AEs for each arm were presented as pre-specified in protocol.	Within 7 days post any vaccination
Number of Participants With Solicited Systemic Reactions	A solicited reaction was an "expected" AR (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRB and considered as related to the product administered. Solicited systemic reactions included fever, vomiting, crying abnormal, drowsiness, appetite loss, and irritability. Reported AEs for each arm were presented as pre-specified in protocol.	Within 7 days post-any vaccination
Number of Participants With Unsolicited Adverse Events	An AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product, and which does not necessarily have a causal relationship with this treatment. An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the CRB in terms of diagnosis and/or onset window post-vaccination. Unsolicited AEs includes both serious adverse events (SAEs) and non-serious unsolicited AEs. Reported AEs for each arm were presented as pre-specified in protocol.	Within 30 days post any vaccination
Number of Participants With Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESIs)	A SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An AESI (serious or non-serious) was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate. Reported AEs for each arm were presented as pre-specified in protocol.	From day of first vaccination (i.e., at the age of 2 months) up to 6 months after last vaccination (i.e., up to the age of 18 months)
Number of Participants With Medically Attended Adverse Event (MAAEs)	A MAAE was defined as a new onset of a condition that prompts the participant or participant's parent/guardian to seek unplanned medical advice at a health care provider's office or Emergency Department. Reported AEs for each arm were presented as pre-specified in protocol.	From day of first vaccination (i.e., at the age of 2 months) up to 6 months after last vaccination (i.e., up to the age of 18 months)

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi Pasteur, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2018
• Primary Completion (Actual): March 16, 2023
• Study Completion (Actual): March 16, 2023

Study Registration Dates

• First Submitted: September 13, 2018
• First Submitted That Met QC Criteria: September 14, 2018
• First Posted (Actual): September 17, 2018

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Meningococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: MET41; U1111-1183-6261 (Other Identifier: WHO); 2019-004459-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No