Clinical trial NCT03632720: Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine in Infants and Toddlers When Administered Concomitantly With Routine Pediatric Vaccines in the United Kingdom
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Healthy Volunteers (Meningococcal Infection)
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2018-08-15
Enrollment: 788
Sex: ALL
Minimum age (years): 56
Maximum age (years): 89
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary objective of the study was to demonstrate the non-inferiority of the antibody responses to meningococcal serogroups A, C, W, and Y (MenACYW) in terms of serum bactericidal assay using human complement (hSBA) vaccine seroprotection (antibody titer greater than or equal to \[\>=\] 1:8) when MenACYW Conjugate vaccine was administered concomitantly with Bexsero® in the second year of life compared to when MenACYW Conjugate vaccine was given alone.

The secondary objectives were 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 was administered concomitantly with Bexsero® or when MenACYW Conjugate vaccine was given alone in the second year of life; to describe the hSBA and serum bactericidal assay using baby rabbit complement (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.

Detailed description: Study duration per participant was approximately 11 to 12 months.

Eligibility criteria: Inclusion Criteria:

* Aged \>= 56 to less than or equal 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 kilogram (kg) (or 5 lb and 8 oz).
* Informed consent form had 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 were 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 was 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, participants with persistent complement deficiency, with anatomic or functional asplenia, or participants 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, was 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 participant should not be included in the study until the condition had 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.

Primary outcomes:
measure: Percentage of Participants With Antibody Titers Greater Than or Equal to (>=) 1:8 Against Meningococcal Serogroups A, C, Y, and W Measured by hSBA After Vaccination: Groups 1 and 2 - PPAS3
timeFrame: 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
Secondary outcomes:
measure: Geometric Mean Titers (GMTs) of Antibodies Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS3
timeFrame: 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Geometric Mean Titers of Antibodies Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W Before Vaccination: Group 1 and 2 - PPAS1
timeFrame: Before vaccination at the age of 3 months
measure: Geometric Mean Titers of Antibodies Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS1
timeFrame: 30 days post-vaccination at the age of 3 months (i.e., at the age of 4 months)
measure: Geometric Mean Titers of Antibodies Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W Before Vaccination: Group 1 and 2 - PPAS3
timeFrame: Before vaccination at the age of 12 to 13 months
measure: Geometric Mean Titers of Antibodies Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS3
timeFrame: 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Geometric Mean Titers of Antibodies Measured by rSBA Against Meningococcal Serogroups A, C, Y, and W Before Vaccination: Group 1 and 2 - PPAS1
timeFrame: Before vaccination at the age of 3 months
measure: Geometric Mean Titers of Antibodies Measured by rSBA Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS1
timeFrame: 30 days post-vaccination at the age of 3 months (i.e., at the age of 4 months)
measure: Geometric Mean Titers of Antibodies Measured by rSBA Against Meningococcal Serogroups A, C, Y, and W Before Vaccination: Group 1 and 2 - PPAS3
timeFrame: Before vaccination at the age of 12 to 13 months
measure: Geometric Mean Titers of Antibodies Measured by rSBA Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS3
timeFrame: 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Percentage of Participants With hSBA Antibody Titers >=1:4 and >=1:8 Against Meningococcal Serogroups A, C, Y, and W Before Vaccination: Group 1 and 2 - PPAS1
timeFrame: Before vaccination at the age of 3 months
measure: Percentage of Participants With hSBA Antibody Titers >=1:4 and >=1:8 Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS1
timeFrame: 30 days post-vaccination at the age of 3 months (i.e., at the age of 4 months)
measure: Percentage of Participants With hSBA Antibody Titers >=1:4 and >=1:8 Against Meningococcal Serogroups A, C, Y, and W Before Vaccination: Group 1 and 2 - PPAS3
timeFrame: Before vaccination at the age of 12 to 13 months
measure: Percentage of Participants With hSBA Antibody Titers >=1:4 and >=1:8 Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS3
timeFrame: 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Percentage of Participants With rSBA Antibody Titers >=1:8 and >=1:128 Against Meningococcal Serogroups A, C, Y, and W Before Vaccination: Group 1 and 2 - PPAS1
timeFrame: Before vaccination at the age of 3 months
measure: Percentage of Participants With rSBA Antibody Titers >=1:8 and >=1:128 Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS1
timeFrame: 30 days post-vaccination at the age of 3 months (i.e., at the age of 4 months)
measure: Percentage of Participants With rSBA Antibody Titers >=1:8 and >=1:128 Against Meningococcal Serogroups A, C, Y, and W Before Vaccination: Group 1 and 2 - PPAS3
timeFrame: Before vaccination at the age of 12 to 13 months
measure: Percentage of Participants With rSBA Antibody Titers >=1:8 and >=1:128 Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS3
timeFrame: 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Percentage of Participants With >= 4-Fold Rise in hSBA Antibody Titers Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS1
timeFrame: Before vaccination at the age of 3 months, 30 days post-vaccination at the age of 3 months (i.e., at the age of 4 months)
measure: Percentage of Participants With >= 4-Fold Rise in hSBA Antibody Titers Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS3
timeFrame: Before vaccination at the age of 3 months, 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Percentage of Participants With >= 4-Fold Rise in hSBA Antibody Titers Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS3
timeFrame: Before vaccination at the age of 12 to 13 months, 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Percentage of Participants With >= 4-Fold Rise in rSBA Antibody Titers Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS1
timeFrame: Before vaccination at the age of 3 months, 30 days post-vaccination at the age of 3 months (i.e., at the age of 4 months)
measure: Percentage of Participants With >= 4-Fold Rise in rSBA Antibody Titers Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS3
timeFrame: Before vaccination at the age of 3 months, 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Percentage of Participants With >= 4-Fold Rise in rSBA Antibody Titers Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS3
timeFrame: Before vaccination at the age of 12 to 13 months, 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Percentage of Participants With Vaccine Seroresponse Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS1
timeFrame: Before vaccination at the age of 3 months up to 30 days post-vaccination at the age of 3 months (i.e., at the age of 4 months)
measure: Percentage of Participants With Vaccine Seroresponse Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS3
timeFrame: Before vaccination at the age of 3 months up to 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Percentage of Participants With Vaccine Seroresponse Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS3
timeFrame: Before vaccination at the age of 12 to 13 months up to 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Percentage of Participants With Vaccine Seroresponse Measured by rSBA Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS1
timeFrame: Before vaccination at the age of 3 months up to 30 days post-vaccination at the age of 3 months (i.e., at the age of 4 months)
measure: Percentage of Participants With Vaccine Seroresponse Measured by rSBA Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS3
timeFrame: Before vaccination at the age of 3 months up to 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Percentage of Participants With Vaccine Seroresponse Measured by rSBA Against Meningococcal Serogroups A, C, Y, and W After Vaccination: Group 1 and 2 - PPAS3
timeFrame: Before vaccination at the age of 12 to 13 months up to 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Percentage of Participants With Distribution of hSBA Titers Against Meningococcal Serogroups A, C, Y, and W Before Vaccination - PPAS1
timeFrame: Before vaccination at the age of 3 months
measure: Percentage of Participants With Distribution of hSBA Titers Against Meningococcal Serogroups A, C, Y, and W After Vaccination - PPAS1
timeFrame: 30 days post-vaccination at the age of 3 months (i.e., at the age of 4 months)
measure: Percentage of Participants With Distribution of hSBA Titers Against Meningococcal Serogroups A, C, Y, and W Before Vaccination - PPAS3
timeFrame: Before vaccination at the age of 12 to 13 months
measure: Percentage of Participants With Distribution of hSBA Titers Against Meningococcal Serogroups A, C, Y, and W After Vaccination - PPAS3
timeFrame: 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Percentage of Participants With Distribution of rSBA Titers Against Meningococcal Serogroups A, C, Y, and W Before Vaccination - PPAS1
timeFrame: Before vaccination at the age of 3 months
measure: Percentage of Participants With Distribution of rSBA Titers Against Meningococcal Serogroups A, C, Y, and W After Vaccination - PPAS1
timeFrame: 30 days post-vaccination at the age of 3 months (i.e., at the age of 4 months)
measure: Percentage of Participants With Distribution of rSBA Titers Against Meningococcal Serogroups A, C, Y, and W Before Vaccination - PPAS3
timeFrame: Before vaccination at the age of 12 to 13 months
measure: Percentage of Participants With Distribution of rSBA Titers Against Meningococcal Serogroups A, C, Y, and W After Vaccination - PPAS3
timeFrame: 30 days post-vaccination at the age of 12 to 13 months (i.e., at the age of 13 to 14 months)
measure: Geometric Mean Titers of Antibodies Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W: Group 1 and 2 - PPAS2
timeFrame: 30 days post-vaccination at the age of 3 months (i.e., at the age of 4 months) and before vaccination at the age of 12-13 months
measure: Percentage of Participants With hSBA Antibody Titers >=1:4 and >=1:8 Against Meningococcal Serogroups A, C, Y, and W - PPAS2
timeFrame: 30 days post-vaccination at the age of 3 months (i.e., at the age of 4 months) and before vaccination at the age of 12-13 months
measure: Geometric Mean Titers of Antibodies Measured by rSBA Against Meningococcal Serogroups A, C, Y, and W: Group 1 and 2 - PPAS2
timeFrame: 30 days post-vaccination at the age of 3 months (i.e., at the age of 4 months) and before vaccination at the age of 12-13 months
measure: Percentage of Participants With rSBA Antibody Titers >=1:8 and >=1:128 Against Meningococcal Serogroups A, C, Y, and W - PPAS2
timeFrame: 30 days post-vaccination at the age of 3 months (i.e., at the age of 4 months) and before vaccination at the age of 12-13 months
measure: Number of Participants With Solicited Injection Site Reactions After Any Vaccination
timeFrame: Within 7 days post any vaccination
measure: Number of Participants With Solicited Systemic Reactions After Any Vaccination
timeFrame: Within 7 days after any vaccination
Other outcomes:
Locations:
city: Newquay
country: United Kingdom
facility: Investigational Site Number :8260024
state: Cornwall
city: Penzance
country: United Kingdom
facility: Investigational Site Number :8260009
state: Cornwall
city: Torpoint
country: United Kingdom
facility: Investigational Site Number :8260013
state: Cornwall
city: Exeter
country: United Kingdom
facility: Investigational Site Number :8260010
state: Devon
city: Poole
country: United Kingdom
facility: Investigational Site Number :8260017
state: Dorset
city: Gloucester
country: United Kingdom
facility: Investigational Site Number :8260018
state: Gloucestershire
city: Bristol
country: United Kingdom
facility: Investigational Site Number :8260001
city: Ivybridge
country: United Kingdom
facility: Investigational Site Number :8260011
city: London
country: United Kingdom
facility: Investigational Site Number :8260002
city: Manchester
country: United Kingdom
facility: Investigational Site Number :8260004
city: Southampton
country: United Kingdom
facility: Investigational Site Number :8260003
city: Taunton
country: United Kingdom
facility: Investigational Site Number :8260006
city: Waterlooville
country: United Kingdom
facility: Investigational Site Number :8260021
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: