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: Recruiting
• First Posted: May 25, 2018
• Last Update Posted: February 9, 2021
• 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: February 9, 2021
• Actual Study Start Date: April 25, 2018
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Current 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 6, 2019)

• 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 ]
• Level of antibody titers against meningococcal serogroups A, C, Y, and W [ Time Frame: Before and 30 days after the 12-month vaccination ]
• Percentage of participants with ≥ 4-fold rise in antibody titers against meningococcal serogroups A, C, Y, and W [ Time Frame: From pre-4th dose to post-4th dose ]
• Level of antibody titers against meningococcal serogroups A, C, Y, and W [ Time Frame: 30 days after 6-month vaccination and before 12-month vaccination ]
• Percentage of participants with antibody titers ≥1:4 and ≥ 1:8 against meningococcal serogroups A, C, Y, and W [ Time Frame: 30 days after 6-month vaccination and before 12-month vaccination ]
• Solicited injection site reactions and systemic reactions [ Time Frame: Within 7 days after vaccination ]

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: Immunogenicity and Safety Study of an Investigational Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers

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.

Primary objectives:

• To demonstrate the non-inferiority of the immune response after a 4-dose series of MenACYW conjugate vaccine compared to a 4-dose series of MENVEO when given concomitantly with routine pediatric vaccines to infants and toddlers 6 weeks to 15 months of age.
• To demonstrate the non-inferiority of the immune response after 3 doses of MenACYW conjugate vaccine compared to 3 doses of MENVEO when given concomitantly with routine pediatric vaccines to infants at 2, 4, and 6 months of age.

Secondary objective:

• To demonstrate the non-inferiority of the immune responses of the routine pediatric vaccines administered concomitantly with MenACYW conjugate vaccine as compared with MENVEO to infants and toddlers 6 weeks to 18 months of age.
• To assess the antibody responses against meningococcal serogroups A, C, Y, and W after the administration of the 4th dose of MenACYW conjugate vaccine as compared with MENVEO® when both are given concomitantly with routine pediatric vaccines at 12 months of age.
• To assess the persistence of bactericidal antibodies at 12 months of age (prior to the 4th dose) in participants who previously received 3 doses of MenACYW conjugate vaccine or MENVEO® in infancy concomitantly with routine pediatric vaccines at 2, 4, and 6 months of age.

Observational objective:

• To describe the safety profile of MenACYW conjugate vaccine and MENVEO when administered concomitantly with routine pediatric vaccines in healthy infants and toddlers

Detailed Description

Healthy infants will be enrolled and randomized to receive either 4 doses of MenACYW conjugate vaccine or 4 doses of the licensed control vaccine, MENVEO®. All participants will receive routine vaccines as per the Advisory Committee on Immunization Practices (ACIP) recommendations.

All participants will be assessed for immunogenicity at baseline (pre-vaccination), and after completing the infant schedule and the second year of life vaccination schedule.

Safety will be assessed throughout the study period, and includes solicited injection site and systemic reactions as well as unsolicited adverse events after each vaccine injection, and serious adverse events occurring throughout the trial.

• 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:

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. During the toddler part of the study, individuals blinded during the infant part of the study might be potentially unblinded due to the different timing of and age of the participants at the vaccination visits and the number of vaccines received during these visits.

Primary Purpose: Prevention

• Condition: Meningococcal Infections

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
• Biological: Pneumococcal 13-valent conjugate vaccine
  Pneumococcal vaccine at 2, 4, 6, and 12 months of age
• Biological: Pentavalent rotavirus vaccine
  Rotavirus vaccine at 2, 4, and 6 months of age
• Biological: Hepatitis B vaccine
  Hepatitis B vaccine at 2 and 6 months of age
• Biological: Measles, mumps, rubella (MMR) vaccine
  MMR vaccine at 12 months of age
• Biological: Varicella vaccine
  Varicella vaccine at 12 months of age
• Biological: Hepatitis A vaccine
  Hepatitis A vaccine at 15 to 18 months of age

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: Recruiting
• Estimated Enrollment (submitted: May 15, 2018): 2475
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2022
• Estimated Primary Completion Date: December 2022 (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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 42 Days to 89 Days (Child)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Trial Transparency Toll free number for US & Canada - e-mail is recommended); 800-633-1610 ext 1 then #; Contact-US@sanofi.com

• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT03537508
• Other Study ID Numbers: MET42
• 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: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available Sanofi continues to protect the privacy of the participants in clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com

• Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
• Study Sponsor: Sanofi Pasteur, a Sanofi Company
• Collaborators: Not Provided

Investigators

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

• PRS Account: Sanofi
• Verification Date: February 2021