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

• ClinicalTrials.gov Identifier: NCT03537508
• Recruitment Status: Active, not recruiting
• First Posted: May 25, 2018
• Last Update Posted: January 4, 2023
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Tracking Information

• First Submitted Date: May 15, 2018
• First Posted Date: May 25, 2018
• Last Update Posted Date: January 4, 2023
• Actual Study Start Date: April 25, 2018
• Estimated Primary Completion Date: October 10, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 4, 2021)

• Antibody titers above predefined thresholds against meningococcal serogroups A, C, Y, and W (Subgroup 1a and 2a) [ Time Frame: D0 and 30 days after the fourth meningococcal vaccination for subgroup 1a and 2a ]
  Percentage of participants achieving a seroresponse, measured by the serum bactericidal assay using human complement (hSBA)
• Antibody titers ≥ 1:8 against meningococcal serogroups A, C, Y, and W (group 1 and 2) [ Time Frame: 30 days after vaccination at 6 months of age for group 1 and 2 ]
  Percentage of participants achieving antibody titers ≥ predefined threshold of 1:8, measured by hSBA

Original Primary Outcome Measures (submitted: May 15, 2018)

• Level of antibody titers against meningococcal serogroups A, C, Y, and W after 4 doses of meningococcal vaccine given concomitantly with routine vaccines [ Time Frame: 30 days after the fourth meningococcal vaccination ]
  Titers are measured by serum bactericidal assay using human complement (hSBA)
• Percentage of participants with antibody titers ≥ 1:8 against meningococcal serogroups A, C, Y, and W after 3 doses of meningococcal vaccine given concomitantly with routine vaccines [ Time Frame: 30 days after vaccination at 6 months of age ]
  Titers are measured by hSBA

Current Secondary Outcome Measures (submitted: August 4, 2021)

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

Original Secondary Outcome Measures (submitted: May 15, 2018)

• IgG antibodies against hepatitis B surface antigen (anti-HB) at concentrations ≥ 10 milli-international units (mIU) / mL after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after vaccination at 6 months of age) [ Time Frame: 30 days after vaccination at 6 months of age ]
• Anti polyribosyl-ribitol phosphate (PRP) antibody concentrations ≥ 0.15 and ≥ 1.0 µg/mL after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after vaccination at 6 months of age) [ Time Frame: 30 days after vaccination at 6 months of age ]
• Anti-poliovirus types 1, 2, and 3 antibody titers ≥ 1:8 after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after vaccination at 6 months of age) [ Time Frame: 30 days after vaccination at 6 months of age ]
• Anti-rotavirus serum IgA antibody concentrations with ≥ 3-fold rise over baseline after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after vaccination at 6 months of age) [ Time Frame: Day 0 (pre-vaccination) and 30 days after vaccination at 6 months of age ]
• Anti-rotavirus serum IgA antibody geometric mean concentrations (GMCs) after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after vaccination at 6 months of age) [ Time Frame: 30 days after vaccination at 6 months of age ]
• Anti-pertussis (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], fimbriae types 2 and 3 [FIM]) antibody concentrations after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after vaccination at 6 months of age) [ Time Frame: Day 0 (pre-vaccination) and 30 days after vaccination at 6 months of age ]
• Anti-pneumococcal antibody concentrations after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after vaccination at 6 months of age) [ Time Frame: 30 days after vaccination at 6 months of age ]
  Anti-pneumococcal antibodies against serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F will be measured
• Anti-measles antibody concentrations ≥ 255 mIU/mL after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 12-month vaccination) [ Time Frame: 30 days after the 12-month vaccination ]
• Anti-mumps antibody concentrations ≥ 10 mumps antibody units/mL after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 12-month vaccination) [ Time Frame: 30 days after the 12-month vaccination ]
• Anti-rubella antibody concentrations ≥ 10 IU/mL after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 12-month vaccination) [ Time Frame: 30 days after the 12-month vaccination ]
• Anti-varicella antibody concentrations ≥ 5 glycoprotein enzyme-linked immunosorbent assay (gpELISA) units/mL after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 12-month vaccination) [ Time Frame: 30 days after the 12-month vaccination ]
• Anti-pneumococcal antibody concentrations after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 12-month vaccination) [ Time Frame: 30 days after the 12-month vaccination ]
  Anti-pneumococcal antibody concentrations against serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F will be measured
• Anti-PRP antibody concentrations ≥ 1.0 µg/mL after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 15-month vaccination) [ Time Frame: 30 days after the 15-month vaccination ]
• Anti-poliovirus types 1, 2, and 3 antibody titers ≥ 1:8 after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 15-month vaccination) [ Time Frame: 30 days after the 15-month vaccinations ]
• Anti-pertussis antibody concentrations (PT, FHA, PRN, and FIM) (seroresponse) after concomitant vaccination with MenACYW conjugate vaccine or MENVEO® (after the 15-month vaccination) [ Time Frame: 30 days after the 15-month vaccination ]
• Solicited injection site reactions and systemic reactions [ Time Frame: Within 7 days after vaccination ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the US
• 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
• Brief 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.
• Detailed 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.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The study is conducted modified double blind for the infant part of the study, with everyone involved in the study (participants/parents, investigators, safety outcome assessor, Sponsor) blinded to the meningococcal vaccine received, except the personnel administering the vaccine.

Primary Purpose: Prevention

• Condition: Healthy Volunteers (Meningococcal Infection)

Intervention

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

Study Arms

• Experimental: Group 1a
  MenACYW conjugate vaccine and routine vaccines at 2, 4, 6, and 12 to 15 months of age
  Interventions:

  • Biological: MenACYW conjugate vaccine
  • Biological: DTaP-IPV//Hib vaccine
  • Biological: Pneumococcal 13-valent conjugate vaccine
  • Biological: Pentavalent rotavirus vaccine
  • Biological: Hepatitis B vaccine
  • Biological: Measles, mumps, rubella (MMR) vaccine
  • Biological: Varicella vaccine
• Experimental: Group 1b
  MenACYW conjugate vaccine at 2, 4, 6, and 15 to 18 months of age and routine vaccines at 2, 4, 6, 12 to 15 months of age, and 15 to 18 months of age
  Interventions:

  • Biological: MenACYW conjugate vaccine
  • Biological: DTaP-IPV//Hib vaccine
  • Biological: Pneumococcal 13-valent conjugate vaccine
  • Biological: Pentavalent rotavirus vaccine
  • Biological: Hepatitis B vaccine
  • Biological: Measles, mumps, rubella (MMR) vaccine
  • Biological: Varicella vaccine
  • Biological: Hepatitis A vaccine
• Active Comparator: Group 2a
  MENVEO® at 2, 4, 6, and 12 months of age and routine vaccines at 2, 4, 6, 12, and 15 to 18 months of age
  Interventions:

  • Biological: MenACYW-135 conjugate vaccine
  • Biological: DTaP-IPV//Hib vaccine
  • Biological: Pneumococcal 13-valent conjugate vaccine
  • Biological: Pentavalent rotavirus vaccine
  • Biological: Hepatitis B vaccine
  • Biological: Measles, mumps, rubella (MMR) vaccine
  • Biological: Varicella vaccine
• Active Comparator: Group 2b
  MENVEO® at 2, 4, 6, and 12 months of age and routine vaccines at 2, 4, 6, 12, and 15 to 18 months of age
  Interventions:

  • Biological: MenACYW-135 conjugate vaccine
  • Biological: DTaP-IPV//Hib vaccine
  • Biological: Pneumococcal 13-valent conjugate vaccine
  • Biological: Pentavalent rotavirus vaccine
  • Biological: Hepatitis B vaccine
  • Biological: Measles, mumps, rubella (MMR) vaccine
  • Biological: Varicella vaccine
  • Biological: Hepatitis A vaccine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: September 27, 2021): 2628
• Original Estimated Enrollment (submitted: May 15, 2018): 2475
• Estimated Study Completion Date: October 10, 2024
• Estimated Primary Completion Date: October 10, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 42 Days to 89 Days (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT03537508
• Other Study ID Numbers: MET42; U1111-1183-6361 ( Registry Identifier: ICTRP )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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

• Current Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
• Original Responsible Party: Same as current
• Current Study Sponsor: Sanofi Pasteur, a Sanofi Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Sanofi Pasteur, a Sanofi Company

• PRS Account: Sanofi
• Verification Date: January 2023