Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine in Infants and Toddlers When Administered Concomitantly With Routine Pediatric Vaccines in the United Kingdom (MET52)

• ClinicalTrials.gov Identifier: NCT03632720
• Recruitment Status: Active, not recruiting
• First Posted: August 15, 2018
• Last Update Posted: September 15, 2022
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

Brief Summary:

The primary objective of the study is to demonstrate the non-inferiority of the antibody responses to meningococcal serogroups A, C, W, and Y in terms of hSBA vaccine seroprotection (antibody titer ≥ 1:8) when MenACYW conjugate vaccine is administered concomitantly with Bexsero® in the second year of life compared to when MenACYW conjugate vaccine is given alone The secondary objective is to compare the hSBA antibody response in terms of geometric mean titers (GMTs) against meningococcal serogroups A, C, W, and Y when MenACYW conjugate vaccine is administered concomitantly with Bexsero® or when MenACYW conjugate vaccine is given alone in the second year of life; to describe the hSBA and rSBA antibody responses against meningococcal serogroups A, C, W, and Y before and after the 1st dose of MenACYW conjugate vaccine administered at 3 months of age, before and after the 2nd dose of MenACYW conjugate vaccine administered at 12 to 13 months of age for Group 1 and Group 2; to describe the hSBA and rSBA antibody persistence against meningococcal serogroups A, C, W, and Y after the 1st dose of MenACYW conjugate vaccine administered at 3 months of age for Group 1 and Group 2

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers (Meningococcal Infection)	Biological: Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine; Biological: Meningococcal group B vaccine; Biological: Diphtheria, tetanus, pertussis (acellular component), hepatitis B, poliomyelitis (inactivated) vaccine; Biological: Human rotavirus RIX4414 strain vaccine; Biological: Pneumococcal 13-valent polysaccharide conjugate vaccine	Phase 3

Detailed Description:

Study duration per participant will be approximately 11 to 12 months

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 788 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety Study of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Infants and Toddlers When Administered Using a 1+1 Schedule in a National Immunization Schedule Having a Meningococcal Group B Vaccine as Standard of Care
• Actual Study Start Date: October 10, 2018
• Estimated Primary Completion Date: January 20, 2023
• Estimated Study Completion Date: January 20, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1; MenACYW conjugate vaccine at 3 months and at 12 to 13 months of age; meningococcal Group B vaccine at 2, 4, and 12 to 13 months of age; routine pediatric vaccines	Biological: Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine; Pharmaceutical form: solution for injection; route of administration: intramuscular, 0.5 mL; Other Name: MenACYW conjugate vaccine; Biological: Meningococcal group B vaccine; Pharmaceutical form: suspension for injection; route of administration: deep intramuscular, 0.5 mL; Other Name: Bexsero®; Biological: Diphtheria, tetanus, pertussis (acellular component), hepatitis B, poliomyelitis (inactivated) vaccine; Pharmaceutical form: powder and suspension for suspension injection; route of administration: deep intramuscular, 0.5 mL; Other Name: Infanrix hexa®; Biological: Human rotavirus RIX4414 strain vaccine; Pharmaceutical form: oral suspension; route of administration: oral, 1.5 mL; Other Name: Rotarix®; Biological: Pneumococcal 13-valent polysaccharide conjugate vaccine; Pharmaceutical form: suspension for injection; route of administration: intramuscular, 0.5 mL; Other Name: Prevenar 13®
Experimental: Group 2; MenACYW conjugate vaccine at 3 months and at 12 to 13 months of age; meningococcal Group B vaccine at 2 and 4 months of age; routine pediatric vaccines	Biological: Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine; Pharmaceutical form: solution for injection; route of administration: intramuscular, 0.5 mL; Other Name: MenACYW conjugate vaccine; Biological: Meningococcal group B vaccine; Pharmaceutical form: suspension for injection; route of administration: deep intramuscular, 0.5 mL; Other Name: Bexsero®; Biological: Diphtheria, tetanus, pertussis (acellular component), hepatitis B, poliomyelitis (inactivated) vaccine; Pharmaceutical form: powder and suspension for suspension injection; route of administration: deep intramuscular, 0.5 mL; Other Name: Infanrix hexa®; Biological: Human rotavirus RIX4414 strain vaccine; Pharmaceutical form: oral suspension; route of administration: oral, 1.5 mL; Other Name: Rotarix®; Biological: Pneumococcal 13-valent polysaccharide conjugate vaccine; Pharmaceutical form: suspension for injection; route of administration: intramuscular, 0.5 mL; Other Name: Prevenar 13®
Active Comparator: Group 3; Meningococcal Group B vaccine at 2, 4, and 12 to 13 months of age; routine pediatric vaccines	Biological: Meningococcal group B vaccine; Pharmaceutical form: suspension for injection; route of administration: deep intramuscular, 0.5 mL; Other Name: Bexsero®; Biological: Diphtheria, tetanus, pertussis (acellular component), hepatitis B, poliomyelitis (inactivated) vaccine; Pharmaceutical form: powder and suspension for suspension injection; route of administration: deep intramuscular, 0.5 mL; Other Name: Infanrix hexa®; Biological: Human rotavirus RIX4414 strain vaccine; Pharmaceutical form: oral suspension; route of administration: oral, 1.5 mL; Other Name: Rotarix®; Biological: Pneumococcal 13-valent polysaccharide conjugate vaccine; Pharmaceutical form: suspension for injection; route of administration: intramuscular, 0.5 mL; Other Name: Prevenar 13®

Outcome Measures

Primary Outcome Measures :

1. Percentage of participants achieving antibody titers against meningococcal serogroups A, C, Y, and W ≥ predefined threshold [ Time Frame: Day 31 ]
   Antibody titers ≥ 1:8 against meningococcal serogroups A, C, Y, and W

Secondary Outcome Measures :

1. Geometric Mean Titers (GMTs) of antibodies against meningococcal serogroups A, C, Y, and W in Group 1 and Group 2 [ Time Frame: 30 days after vaccination with MenACYW conjugate vaccine concomitantly with Bexsero® (Group 1) or alone at 12 to 13 months of age (Group 2) ]
   Antibody titers (hSBA) are expressed as GMTs
2. GMTs of antibodies (hSBA and rSBA) against meningococcal serogroups A, C, Y, and W [ Time Frame: Before and 30 days after the first dose of MenACYW conjugate vaccine administered at 3 months of age, before and 30 days after the second dose of MenACYW conjugate vaccine administered at 12 to 13 months of age ]
   Antibody titers (hSBA and rSBA) are expressed as GMTs
3. hSBA antibody titer above predefined threshold in participants [ Time Frame: Before and 30 days after the first dose of MenACYW conjugate vaccine administered at 3 months of age, before and 30 days after the second dose of MenACYW conjugate vaccine administered at 12 to 13 months of age ]
   hSBA antibody titer ≥ 1:4 and titers ≥ 1:8
4. rSBA antibody titer above predefined threshold in participants [ Time Frame: Before and 30 days after the first dose of MenACYW conjugate vaccine administered at 3 months of age, before and 30 days after the second dose of MenACYW conjugate vaccine administered at 12 to 13 months of age ]
   rSBA antibody titer ≥ 1:8 and titers ≥ 1:128
5. Antibody titer above predefined threshold in participants [ Time Frame: Before and 30 days after the first dose of MenACYW conjugate vaccine administered at 3 months of age, before and 30 days after the second dose of MenACYW conjugate vaccine administered at 12 to 13 months of age ]
   Antibody titer ≥ 4-fold rise from pre-vaccination to post-vaccination
6. Percentage of participants with hSBA and rSBA vaccine seroresponse [ Time Frame: Before and 30 days after the first dose of MenACYW conjugate vaccine administered at 3 months of age, before and 30 days after the second dose of MenACYW conjugate vaccine administered at 12 to 13 months of age ]

   hSBA vaccine seroresponse for serogroups A, C, W, and Y defined as:

   • if pre-vaccination titer < 1:8, post-vaccination titer must be ≥ 1:16
   • if pre-vaccination titer ≥ 1:8, post-vaccination titer must be ≥ 4-fold greater than the pre-vaccination titer rSBA vaccine seroresponse for serogroups A, C, W, and Y defined as:
   • if pre-vaccination titer < 1:8, post-vaccination titer must be ≥ 1:32
   • if pre-vaccination titer ≥ 1:8, post-vaccination titer must be ≥ 4-foldgreater than the pre-vaccination titer
7. GMTs of antibodies (hSBA and rSBA) against meningococcal serogroups A, C, Y, and W [ Time Frame: 30 days after the first dose of MenACYW conjugate vaccine administered at 3 months of age, and before the second dose of MenACYW conjugate vaccine administered at 12 to 13 months of age ]
   Antibody titers (hSBA and rSBA) are expressed as GMTs
8. hSBA antibody titer above predefined threshold in participants [ Time Frame: 30 days after the first dose of MenACYW conjugate vaccine administered at 3 months of age, and before the second dose of MenACYW conjugate vaccine administered at 12 to 13 months of age ]
   hSBA antibody titer ≥ 1:4 and titers ≥ 1:8
9. rSBA antibody titer above predefined threshold in participants [ Time Frame: 30 days after the first dose of MenACYW conjugate vaccine administered at 3 months of age, and before the second dose of MenACYW conjugate vaccine administered at 12 to 13 months of age ]
   rSBA antibody titer ≥ 1:8 and titers ≥ 1:128
10. Solicited injection site reactions and systemic reactions [ Time Frame: 7 days after each vaccination ]
    Injection site reactions: pain, erythema, and swelling; Systemic reactions: fever, vomiting, crying abnormal, drowsiness, appetite lost, and irritability

Eligibility Criteria

• Ages Eligible for Study: 56 Days to 89 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Aged ≥ 56 to ≤ 89 days on the day of the first study visit
• Born at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥ 2.5 kg (or 5 lb and 8 oz)
• Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative (and by an independent witness if required by local regulations)
• Participant and parent/legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures

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 (at Visit 1) 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 vaccines. 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, W, or Y; or meningococcal B serogroup-containing vaccine)
• Previous vaccination (before Visit 1) with any pneumococcal, diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b (Hib), poliovirus, and/or rotavirus vaccines. Receipt of BCG vaccine at birth is acceptable
• Receipt of immune globulins, blood or blood-derived since birth
• Known or suspected congenital or acquired immunodeficiency, including Severe Combined Immunodeficiency disorder (SCID); 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
• History of any neurologic disorders, including any seizures and progressive neurologic disorders or encephalopathy
• History of Neisseria meningitidis infection, confirmed either clinically, serologically, or microbiologically
• History of diphtheria, tetanus, pertussis, poliomyelitis, Hib, hepatitis 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 Guillain-Barré syndrome
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances including neomycin, kanamycin, polymyxin, formaldehyde, and latex
• Hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency
• History of intussusception or uncorrected congenital malformation of the gastrointestinal tract that would predispose to intussusception
• 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
• Chronic illness 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, including planning to leave the area of the study site before the end of the study
• Moderate or severe acute illness/infection (according to investigator judgment), or febrile illness (temperature ≥ 38.0°C), or diarrhea or vomiting on the day of vaccination. A prospective subject 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.

Contacts and Locations

Locations

United Kingdom

Investigational Site Number :8260024

Newquay, Cornwall, United Kingdom, TR7 1RU

Investigational Site Number :8260009

Penzance, Cornwall, United Kingdom, TR19 7HX

Investigational Site Number :8260013

Torpoint, Cornwall, United Kingdom, PL11 2TB

Investigational Site Number :8260010

Exeter, Devon, United Kingdom, EX2 5DW

Investigational Site Number :8260017

Poole, Dorset, United Kingdom, BH15 2HX

Investigational Site Number :8260018

Gloucester, Gloucestershire, United Kingdom, GL1 3NN

Investigational Site Number :8260001

Bristol, United Kingdom, BS2 8AE

Investigational Site Number :8260011

Ivybridge, United Kingdom, PL21 OAJ

Investigational Site Number :8260002

London, United Kingdom, SW 17 ORE

Investigational Site Number :8260004

Manchester, United Kingdom, M13 9WL

Investigational Site Number :8260003

Southampton, United Kingdom, SO16 6YD

Investigational Site Number :8260006

Taunton, United Kingdom, TA1 5DA

Investigational Site Number :8260021

Waterlooville, United Kingdom, PO8 8DL

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT03632720
• Other Study ID Numbers: MET52; 2017-004520-30 ( EudraCT Number ); U1111-1183-6530 ( Registry Identifier: ICTRP )
• First Posted: August 15, 2018
• Last Update Posted: September 15, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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

• 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.: Yes

Additional relevant MeSH terms:

Meningococcal Infections; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs