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

Healthy Volunteers (Meningococcal Infection) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03537508
• Other study ID #: MET42
• Secondary ID: U1111-1183-6361
• Status: Completed
• Phase: Phase 3
• Start date: April 25, 2018
• Est. completion date: September 22, 2023

Study information

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

Clinical Trial Summary

The purpose of this study is 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2637
• Est. completion date: September 22, 2023
• Est. primary completion date: September 22, 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 has been signed and dated by the parent(s) or guardian, and an independent witness, if required by local regulations

• Participant and parent/guardian are 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 may be received at a gap of 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, 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, 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 = 38.0°C [= 100.4°F]). 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 is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Healthy Volunteers (Meningococcal Infection)
• Meningococcal Infections

Intervention

Biological:
• MenACYW conjugate vaccine
Meningococcal polysaccharide (serogroups A, C, Y, and W) tetanus toxoid conjugate vaccine 0.5 mL, intramuscular
• MenACYW-135 conjugate vaccine
Meningococcal (Groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine, 0.5 mL, intramuscular
• DTaP-IPV//Hib vaccine
DTaP-IPV//Hib vaccine at 2, 4, and 6 months of age, Intramuscular
• Pneumococcal 13-valent conjugate vaccine
Pneumococcal vaccine at 2, 4, 6, and 12 months of age, Intramuscular
• Pentavalent rotavirus vaccine
Rotavirus vaccine at 2, 4, and 6 months of age, oral solution
• Hepatitis B vaccine
Hepatitis B vaccine at 2 and 6 months of age, Intramuscular
• Measles, mumps, rubella (MMR) vaccine
MMR vaccine at 12 months of age, Subcutaneous
• Varicella vaccine
Varicella vaccine at 12 months of age
• Hepatitis A vaccine
Hepatitis A vaccine at 15 to 18 months of age

Locations

Country	Name	City	State
Puerto Rico	Investigational Site Number : 6300116	Caguas
Puerto Rico	Investigational Site Number : 6300122	Guayama
Puerto Rico	Investigational Site Number : 6300015	San Juan
Puerto Rico	Investigational Site Number : 6300117	San Juan
Puerto Rico	Investigational Site Number : 6300140	San Juan
United States	Emmaus Research Center, Inc Site Number : 8400031	Anaheim	California
United States	ARC Clinical Research at Wilson Parke Site Number : 8400059	Austin	Texas
United States	MedPharmics Biloxi Site Number : 8400080	Biloxi	Mississippi
United States	Birmingham Pediatric Associates Site Number : 8400026	Birmingham	Alabama
United States	Blue Pediatric & Adolescent Medicine Group Site Number : 8400100	Boone	North Carolina
United States	Craig Spiegel, MD Site Number : 8400037	Bridgeton	Missouri
United States	Asclepes Research Centers Site Number : 8400064	Brooksville	Florida
United States	Baybol Research Institute Site Number : 8400008	Chamblee	Georgia
United States	Coastal Pediatric Research Charleston Site Number : 8400005	Charleston	South Carolina
United States	Ericksen Research and Development Site Number : 8400016	Clinton	Utah
United States	Oak Cliff Research Company, LLC Site Number : 8400065	Dallas	Texas
United States	Ohio Pediatric Research Site Number : 8400084	Dayton	Ohio
United States	PriMed Clinical Research Site Number : 8400002	Dayton	Ohio
United States	Avail Clinical Research Site Number : 8400077	DeLand	Florida
United States	Southeastern Pediatric Associates Site Number : 8400003	Dothan	Alabama
United States	Premier Health Research Center Site Number : 8400007	Downey	California
United States	Allegheny Health and Wellness Pavilion Site Number : 8400047	Erie	Pennsylvania
United States	Qualmedica Research, LLC Site Number : 8400106	Evansville	Indiana
United States	Northwest Arkansas Pediatric Clinic Site Number : 8400011	Fayetteville	Arkansas
United States	Helios Clinical research Site Number : 8400075	Fort Worth	Texas
United States	University of North Texas Site Number : 8400079	Fort Worth	Texas
United States	University of Maryland at The Pediatric Center of Frederick Site Number : 8400004	Frederick	Maryland
United States	University of Texas Medical Board Site Number : 8400067	Galveston	Texas
United States	Tribe Clinical Research Site Number : 8400110	Greenville	South Carolina
United States	Cyn3rgy Research Site Number : 8400085	Gresham	Oregon
United States	ACC Pediatric Reasearch Site Number : 8400023	Haughton	Louisiana
United States	Next Phase Research Alliance Site Number : 8400057	Hialeah	Florida
United States	Homestead Medical Clinic, P.A. Site Number : 8400014	Homestead	Florida
United States	Next Phase Research Alliance Site Number : 8400040	Homestead	Florida
United States	Clinical Trial Network - 7080 Southwest Fwy Site Number : 8400114	Houston	Texas
United States	Ventavia Research Group, LLC Site Number : 8400109	Houston	Texas
United States	Marshall Health Site Number : 8400062	Huntington	West Virginia
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	Snake River Research, PLLC Site Number : 8400073	Idaho Falls	Idaho
United States	The Children's Clinic of Jonesboro, PA Site Number : 8400032	Jonesboro	Arkansas
United States	Wee Care Pediatrics Site Number : 8400035	Kaysville	Utah
United States	Children's Research, LLC Site Number : 8400063	Lake Mary	Florida
United States	FMC SCIENCE Site Number : 8400053	Lampasas	Texas
United States	Tanner Clinic Site Number : 8400018	Layton	Utah
United States	Matrix Clinical Research Site Number : 8400095	Los Angeles	California
United States	All Children Pediatrics Site Number : 8400043	Louisville	Kentucky
United States	Brownsboro Park Pediatrics Site Number : 8400010	Louisville	Kentucky
United States	Axcess Medical Research Site Number : 8400068	Loxahatchee Groves	Florida
United States	Velocity Clinical Research Site Number : 8400025	Metairie	Louisiana
United States	Acevedo Clinical Research Associates Site Number : 8400001	Miami	Florida
United States	Tiga Pediatrics Site Number : 8400137	New York	New York
United States	Creighton University Site Number : 8400039	Omaha	Nebraska
United States	Florida Hospital Medical Group Pediatrics Site Number : 8400108	Orlando	Florida
United States	IMIC Inc Site Number : 8400022	Palmetto Bay	Florida
United States	Center for Clinical Trials, LLC Site Number : 8400030	Paramount	California
United States	MedPharmics, LLC - Phoenix Site Number : 8400083	Phoenix	Arizona
United States	Pediatric Care Site Number : 8400056	Provo	Utah
United States	Wee Care Pediatrics Roy Site Number : 8400029	Roy	Utah
United States	Tekton Research Site Number : 8400128	San Antonio	Texas
United States	Tekton Research, Inc Site Number : 8400049	San Antonio	Texas
United States	LSUHSC-Shreveport Site Number : 8400120	Shreveport	Louisiana
United States	Virgo-Carter Pediatrics Site Number : 8400041	Silver Spring	Maryland
United States	Parkside Pediatrics - Simpsonville Site Number : 8400113	Simpsonville	South Carolina
United States	Copperview Medical Center Site Number : 8400038	South Jordan	Utah
United States	Alliance for Multispecialty Research Syracuse Site Number : 8400036	Syracuse	Utah
United States	Wee Care Pediatrics Site Number : 8400024	Syracuse	Utah
United States	Jedidiah Clinical Research Site Number : 8400132	Tampa	Florida
United States	Pediatric Clinical Trials Tullahoma Site Number : 8400033	Tullahoma	Tennessee
United States	Center for Clinical Trials of San Gabriel Site Number : 8400076	West Covina	California

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	Antibody titers above predefined thresholds against meningococcal serogroups A, C, Y, and W (Subgroup 1a and 2a)	Percentage of participants achieving a seroresponse, measured by the serum bactericidal assay using human complement (hSBA)	D0 and 30 days after the fourth meningococcal vaccination for subgroup 1a and 2a
Primary	Antibody titers = 1:8 against meningococcal serogroups A, C, Y, and W (group 1 and 2)	Percentage of participants achieving antibody titers = predefined threshold of 1:8, measured by hSBA	30 days after vaccination at 6 months of age for group 1 and 2
Secondary	IgG antibody concentrations = 10 milli-international units (mIU) / mL against hepatitis B	Percentage of participants who achieving IgG antibody concentrations = predefined threshold of 10 mIU/mL	30 days after vaccination at 6 months of age for group 1 and 2
Secondary	IgG antibody concentrations against hepatitis B	Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations (GMCs)	30 days after vaccination at 6 months of age for group 1 and group 2
Secondary	Antibody concentrations against polyribosyl-ribitol phosphate (PRP)	Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations (GMCs)	30 days after vaccination at 6 months, before and 30 days after 15-months vaccination for subgroup 1b and 2b
Secondary	Antibody concentrations = 0.15 and/or = 1.0 µg/mL against PRP	Percentage of subjects achieving antibody concentrations = predefined thresholds of 0.15 µg/mL and/or 1.0 µg/mL	30 days after vaccination at 6 months of age for group 1 and group 2, before and 30 days after vaccination at 15 months of age for subgroup 1b and 2b
Secondary	Antibody concentrations above predefined threshold against diphteria and tetanus	% of participants with antibody concentrations = established serostatus cut-off levels for diphteria and tetanus	30 days after vaccination at 6 months for group 1 and 2, 30 days after 15-months vaccination for subgroup 1b and 2b
Secondary	Antibody concentrations against diphteria and tetanus	Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations (GMCs)	30 days after vaccination at 6 months for group 1 and 2, 30 days after 15-months vaccination for subgroup 1b and 2b
Secondary	Antibody titers = 1:8 against poliovirus types 1, 2, and 3	Percentage of participants achieving antibody titers = predefined threshold of 1:8	30 days after vaccination at 6 months for group 1 and group 2, 30 days after vaccination at 15 months of age for subgroup 1b and 2b
Secondary	Antibody titers against poliovirus types 1,2,3	Antibody titers will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean titers (GMTs)	30 days after vaccination at 6 months of age for group 1 and group 2, 30 days after vaccination at 15 months of age for subgroup 1b and 2b
Secondary	IgA antibody concentrations with = 3-fold rise over baseline for antigens of 5 serogroups of rotavirus	Percentage of participants achieving IgA antibody concentrations = predefined threshold of 3-fold rise over baseline	D0 and 30 days after vaccination at 6 months of age for group 1 and 2
Secondary	IgA antibody concentrations against antigens of 5 serogroups of rotavirus	Antibody concentrations will be measured by standard assays for the antigens contained in the rotavirus vaccine and expressed as geometric mean concentrations (GMCs)	D0 and 30 days after vaccination at 6 months of age for group 1 and 2
Secondary	Antibody concentrations against pertussis (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], fimbriae types 2 and 3 [FIM])	Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations (GMCs)	D0 and 30 days after vaccination at 6- months of age for group 1 and 2, before and after the 15-months vaccinations for subgroup 1b and 2b
Secondary	Antibody concentrations above predefined threshold against pertussis (PT, FHA, PRN, FIM)	% of participants with antibody concentrations = established seroresponse rate for pertussis	before and after the vaccination at 15 months of age for subgroup 1b and 2b
Secondary	Antibody concentrations against antigens of 13-valent pneumococcal vaccine	Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations (GMCs)	30 days after vaccination at 6 months for group 1 and 2, 30 days after vaccination at 12 months for subgroup 1a and 2a
Secondary	Antibody concentrations above predefined thresholds for antigens of MMR vaccine	% of participants with antibody concentrations = established serostatus cut-off levels for antigens in MMR vaccine	30 days after the 12-month vaccination for subgroup 1a and 2a
Secondary	Antibody concentrations against antigens of MMR vaccine	Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations (GMCs)	30 days after the 12-month vaccination for subgroup 1a and 2a
Secondary	Antibody concentrations against antigens of varicella vaccine	Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations (GMCs)	30 days after the 12-month vaccination for subgroup 1a and 2a
Secondary	Antibody concentrations above predefined thresholds for antigens of varicella vaccine	% of participants with antibody concentrations = established serostatus cut-off levels for antigens in varicella vaccine	30 days after the 12-month vaccination for subgroup 1a and 2a
Secondary	Antibody against meningococcal serogroups A, C, Y, and W	Antibody titers will be measured by hSBA and expressed as geometric mean titers (GMTs)	D0, 30 days after the 6-month age vaccination for group 1 and 2, before and 30 days after the 12-month vaccination for subgroup 1a and 2a, before and after the 15-month vaccination for subgroup 1b
Secondary	Antibody titers above pre-defined thresholds for meningococcal serogroups A, C, Y, and W	% of participants achieving antibody titers = predefined thresholds, measured by hSBA	30 days after the 6-month age vaccination for group 1 and 2, before and 30 days after the 12-month vaccination for subgroup 1a and 2a, before and after the 15-month vaccination for subgroup 1b