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

Healthy Volunteers (Meningococcal Infection) Clinical Trial

— MET41  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03673462
• Other study ID #: MET41
• Secondary ID: U1111-1183-62612
• Status: Completed
• Phase: Phase 3
• Start date: September 17, 2018
• Est. completion date: March 16, 2023

Study information

• Verified date: December 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2797
• Est. completion date: March 16, 2023
• Est. primary completion date: March 16, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 42 Days to 89 Days

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers (Meningococcal Infection)
• Meningococcal Infections

Intervention

Biological:
• Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid Conjugate vaccine (MenACYW Conjugate vaccine)
Pharmaceutical form: Liquid solution. Route of administration: Intramuscular
• 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
• Diphtheria, Tetanus, Acellular Pertussis, Poliovirus and Haemophilus b Vaccine
Pharmaceutical form: Liquid DTaP-IPV to reconstitute lyophilized ActHIB Route of administration: Intramuscular
• Pneumococcal 13-valent Conjugate Vaccine
Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
• Rotavirus Vaccine
Pharmaceutical form: Oral solution Route of administration: Oral
• Hepatitis B Vaccine
Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
• Measles, Mumps, and Rubella Virus Vaccine
Pharmaceutical form: Lyophilized live virus vaccine Route of administration: Subcutaneous
• Varicella Virus Vaccine
Pharmaceutical form: Suspension for injection Route of administration: Subcutaneous

Locations

Country	Name	City	State
Puerto Rico	Investigational Site Number :6300014	San Juan
Puerto Rico	Investigational Site Number :6300108	San Juan
United States	Emmaus Research Center, Inc-Site Number:8400057	Anaheim	California
United States	ARC Clinical Research at Wilson Parke-Site Number:8400071	Austin	Texas
United States	Advanced Clinical Research - Rancho Paseo-Site Number:8400087	Banning	California
United States	Kentucky Pediatics / Adult Research-Site Number:8400044	Bardstown	Kentucky
United States	Rainbow Pediatrics-Site Number:8400074	Barnwell	South Carolina
United States	The Children's Center Rehabilitation Hospital-Site Number:8400104	Bethany	Oklahoma
United States	MedPharmics Biloxi-Site Number:8400052	Biloxi	Mississippi
United States	Birmingham Pediatric Associates-Site Number:8400049	Birmingham	Alabama
United States	Craig Spiegel, MD-Site Number:8400067	Bridgeton	Missouri
United States	PMG Research-Bristol-Site Number:8400009	Bristol	Tennessee
United States	Benchmark Research - Buda-Site Number:8400016	Buda	Texas
United States	Coastal Pediatric Research Charleston-Site Number:8400037	Charleston	South Carolina
United States	Pediatric Medical Research of Charlottesville-Site Number:8400077	Charlottesville	Virginia
United States	Tanner Clinic-Site Number:8400079	Clinton	Utah
United States	Optum Clinical Research-Site Number:8400076	Colorado Springs	Colorado
United States	Crossroads Clinical Research-Site Number:8400058	Corpus Christi	Texas
United States	Ohio Pediatric Research-Site Number:8400064	Dayton	Ohio
United States	PriMed Clinical Research-Site Number:8400033	Dayton	Ohio
United States	Avail Clinical Research, LLC-Site Number:8400055	DeLand	Florida
United States	Southeastern Pediatric Associates-Site Number:8400034	Dothan	Alabama
United States	Premier Health Research Center, LLC-Site Number:8400039	Downey	California
United States	Pediatric Associates of Fall River-Site Number:8400103	Fall River	Massachusetts
United States	Northwest Arkansas Pediatric Clinic-Site Number:8400042	Fayetteville	Arkansas
United States	Advanced Research for Health Improvement-Site Number:8400096	Fort Myers	Florida
United States	Sarkis Clinical Trials-Site Number:8400003	Gainesville	Florida
United States	Medication Management-Site Number:8400072	Greensboro	North Carolina
United States	Cyn3rgy Research-Site Number:8400035	Gresham	Oregon
United States	HealthStar Research, LLC-Site Number:8400100	Hot Springs	Arkansas
United States	The Children's Clinic of Jonesboro, PA-Site Number:8400059	Jonesboro	Arkansas
United States	Center for Pharmaceutical Research-Site Number:8400080	Kansas City	Missouri
United States	Wee Care Pediatrics-Site Number:8400065	Kaysville	Utah
United States	Holston Medical Group, Pediatrics at Stone Plaza-Site Number:8400015	Kingsport	Tennessee
United States	Midwest Childrens Health Research Institute-Site Number:8400060	Lincoln	Nebraska
United States	All Children Pediatrics-Site Number:8400069	Louisville	Kentucky
United States	Brownsboro Park Pediatrics-Site Number:8400040	Louisville	Kentucky
United States	University of Louisville-Site Number:8400082	Louisville	Kentucky
United States	Meridian Clinical Research-Site Number:8400114	Macon	Georgia
United States	Marshfield Clinic-Site Number:8400054	Marshfield	Wisconsin
United States	MedPharmics-Site Number:8400048	Metairie	Louisiana
United States	Acevedo Clinical Research Associates-Site Number:8400032	Miami	Florida
United States	De Armas Research Center,-Site Number:8400088	Miami	Florida
United States	Healthy Life Research-Site Number:8400075	Miami	Florida
United States	Crystal Biomedical Research-Site Number:8400018	Miami Lakes	Florida
United States	MOC Research-Site Number:8400095	Mishawaka	Indiana
United States	PMG Research of Charleston, LLC-Site Number:8400102	Mount Pleasant	South Carolina
United States	Murray Pediatrics-Site Number:8400019	Murray	Utah
United States	Advanced Research for Health Improvement-Site Number:8400005	Naples	Florida
United States	Palmetto Pediatrics, PA-Site Number:8400089	North Charleston	South Carolina
United States	Utah Valley Pediatrics - Timpanogos-Site Number:8400038	Orem	Utah
United States	Center for Clinical Trials, LLC-Site Number:8400056	Paramount	California
United States	MedPharmics, LLC - Phoenix-Site Number:8400043	Phoenix	Arizona
United States	Pediatric Care-Site Number:8400045	Provo	Utah
United States	Legacy Pediatrics-Site Number:8400004	Rochester	New York
United States	Foothill Family Research-South-Site Number:8400036	Salt Lake City	Utah
United States	J. Lewis Research-Site Number:8400053	Salt Lake City	Utah
United States	Benchmark Research - San Angelo-Site Number:8400011	San Angelo	Texas
United States	Southwest Children's Research Associates, P.A.-Site Number:8400002	San Antonio	Texas
United States	Senders Pediatrics-Site Number:8400061	South Euclid	Ohio
United States	Copperview Medical Center-Site Number:8400068	South Jordan	Utah
United States	J Lewis Research Inc-Site Number:8400050	South Jordan	Utah
United States	Alliance for Multispecialty Research Syracuse-Site Number:8400066	Syracuse	Utah
United States	IMMUNOe Research Centers - Thornton-Site Number:8400022	Thornton	Colorado
United States	Pediatric Clinical Trials Tullahoma-Site Number:8400062	Tullahoma	Tennessee
United States	Oklahoma State University - Center for Health Sciences-Site Number:8400008	Tulsa	Oklahoma
United States	Center for Clinical Trials of San Gabriel-Site Number:8400051	West Covina	California
United States	Center for Clinical Trials of San Gabriel-Site Number:8400099	West Covina	California
United States	Ford, Simpson, Lively & Rice Pediatrics-Site Number:8400021	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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)
Primary	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)