Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the Russian Federation and Mexico (MET33)

• ClinicalTrials.gov Identifier: NCT03630705
• Recruitment Status: Completed
• First Posted: August 15, 2018
• Last Update Posted: May 12, 2022
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Tracking Information

• First Submitted Date: August 3, 2018
• First Posted Date: August 15, 2018
• Last Update Posted Date: May 12, 2022
• Actual Study Start Date: October 17, 2018
• Actual Primary Completion Date: February 18, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 9, 2022)

Antibody titers against meningococcal serogroups A, C, Y, and W [ Time Frame: Before the first vaccination and 30 days after the last vaccination in second year of life (Dose 3 of MenACYW conjugate vaccine and Dose 4 of Menveo®) ]

1. Meningococcal serogroups A, C, Y, and W antibody titers ≥1:8 measured by hSBA, assessed at 30 days after the last vaccination in the second year of life with MenACYW conjugate vaccine or Menveo® in Mexico (Group 1 and Group 2)
2. Meningococcal serogroups A, C, Y, and W antibody titers ≥1:8 measured by hSBA assessed at 30 days after the last vaccination in the second year of life with MenACYW conjugate vaccine in the Russian Federation (Group 3)

Original Primary Outcome Measures (submitted: August 9, 2018)

Antibody titers against meningococcal serogroups A, C, Y, and W [ Time Frame: Day 0 (pre-vaccination ) and Day 30 after the last vaccination in second year of life (Dose 3 of MenACYW conjugate vaccine and Dose 4 of Menveo®) ]

Titers are measured by serum bactericidal assay using human complement (hSBA), and expressed as geometric mean titers (GMTs)

Current Secondary Outcome Measures (submitted: February 9, 2022)

• Antibody titers against meningococcal serogroups A, C, Y, and W after infant series vaccination [ Time Frame: Before the first vaccination,30 days after the last vaccination of the infant series and 30 days after the last vaccination in the second year of life (Dose 2 of MenACYW conjugate vaccine and Dose 3 of Menveo®) ]
  1. Meningococcal serogroups A, C, Y, and W antibody titers measured by hSBA, before the first vaccination (Visit 1) and 30 days after the last vaccination of the infant series and 30 days after the last vaccination in the second year of life with MenACYW conjugate vaccine or Menveo® (Dose 2 of MenACYW conjugate vaccine and Dose 3 of Menveo®) in Mexico (Group 1 and Group 2) (vaccine seroresponse)
  2. Meningococcal serogroups A, C, Y, and W antibody titers measured by hSBA, before the first vaccination (Visit 1) and 30 days after the last vaccination of the infant series and 30 days after the last vaccination in the second year of life with MenACYW conjugate vaccine (Dose 2 of MenACYW conjugate vaccine) in the Russian Federation (Group 3) (vaccine seroresponse)
• Anti-pertussis (pertussis toxoid [PT], filamentous hemagglutinin [FHA] antibody concentrations (all groups) [ Time Frame: D0 (before the first vaccinations with Hexacima® and RotaTeq®), 30 days after the 12-months vaccinations with M-M-R®II, Prevnar 13®, and Hexacima® ]
• Anti-rotavirus serum IgA antibody concentrations before first vaccination (group 1 and 2) [ Time Frame: D0 (before the first vaccinations with Hexacima® and RotaTeq®) ]
• Anti-pneumococcal antibody concentrations after vaccinations (group 1 and 2) [ Time Frame: 30 days after the 6-months vaccinations with Prevnar 13® and RotaTeq® ]
  Anti-pneumococcal antibody concentrations for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F will be measured
• Anti-rotavirus serum IgA antibody concentrations with ≥ 3-fold and ≥4-fold rise over baseline after vaccinations (group 1 and 2) [ Time Frame: 30 days after the 6-months vaccinations with Prevnar 13® and RotaTeq® ]
• Anti-measles antibody concentrations ≥ 255 mIU/mL after vaccinations (all groups) [ Time Frame: 30 days after the 12-months vaccinations with M-M-R®II, Prevnar 13®, and Hexacima® ]
• Anti-mumps antibody concentrations ≥ 10 mumps antibody units/mL after vaccinations (all groups) [ Time Frame: 30 days after the 12-months vaccinations with M-M-R®II, Prevnar 13®, and Hexacima® ]
• Anti-rubella antibody concentrations ≥ 10 IU/mL after vaccinations (all groups) [ Time Frame: 30 days after the 12-months vaccinations with M-M-R®II, Prevnar 13®, and Hexacima® ]
• Anti-tetanus antibody concentrations ≥ 0.1 IU / mL and 1.0 IU / mL after vaccinations (all groups) [ Time Frame: 30 days after the 6-months vaccinations with Pentaxim® and ENGERIX-B® and the 12-months vaccinations with M-M-R®II, Prevnar 13®, and Hexacima® ]
• Anti-diphtheria antibody concentrations ≥ 0.1 IU / mL and 1.0 IU / mL after vaccinations (all groups) [ Time Frame: 30 days after the 6-months vaccinations with Pentaxim® and ENGERIX-B® and the 12-months vaccinations with M-M-R®II, Prevnar 13®, and Hexacima® ]
• Anti-poliovirus types 1, 2, and 3 antibody titers ≥ 1:8 after vaccinations (all groups) [ Time Frame: 30 days after the 6-months vaccinations with Pentaxim® and ENGERIX-B® and the 12-months vaccinations with M-M-R®II, Prevnar 13®, and Hexacima® ]
• Anti polyribosyl-ribitol phosphate (PRP) antibody concentrations ≥ 0.15 and ≥ 1.0 µg/mL after vaccinations (all groups) [ Time Frame: 30 days after the 6-months vaccinations with Pentaxim® and ENGERIX-B® and the 12-months vaccinations with M-M-R®II, Prevnar 13®, and Hexacima® ]
• IgG antibodies against hepatitis B surface antigen (anti-HB) at concentrations ≥ 10 milli-international units (mIU) / mL and 100 mIU / mL after vaccinations (all groups) [ Time Frame: 30 days after the 6-months vaccinations with Pentaxim® and ENGERIX-B® and the 12-months vaccinations with M-M-R®II, Prevnar 13®, and Hexacima® ]
• hSBA meningococcal serogroups A, C, Y, and W antibody titers (group 1, 2 and 3) [ Time Frame: D0, 30 days after the 6-month vaccination with MenACYW conjugate vaccine and 30 days after the 12-month vaccination with MenACYW or with Menveo ]
• Antibody titers above pre-defined thresholds against meningococcal serogroups A, C, Y, and W measured by hSBA (group 1, 2 and 3) [ Time Frame: D0, 30 days after 6-month vaccination with MenACYW conjugate vaccine (gr 1 and 3) and with Menveo (gr 2) and 30 days after the 12-month vaccination with MenACYW conjugate vaccine or Menveo ]
• Titer distribution and reverse cumulative distribution curves (RCDCs) (group 1, 2 and 3) [ Time Frame: D0, 30 days after 6-month vaccination with MenACYW conjugate vaccine (gr 1 and 3) and with Menveo (gr 2) and 30 days after the 12-month vaccination with MenACYW conjugate vaccine or Menveo ]
• hSBA meningococcal serogroups A, C, Y, and W vaccine seroresponse [ Time Frame: D0, 30 days after 6-month vaccination with MenACYW conjugate vaccine (gr 1 and 3) and with Menveo (gr 2) and 30 days after the 12-month vaccination with MenACYW conjugate vaccine or Menveo ]

Original Secondary Outcome Measures (submitted: August 9, 2018)

• Antibody titers against meningococcal serogroups A, C, Y, and W after infant series vaccination [ Time Frame: Day 0 (pre-vaccination) and Day 30 after the last vaccination of the infant series (Dose 2 of MenACYW conjugate vaccine and Dose 3 of Menveo®) ]
  Titers are expressed as GMTs
• Number of participants with Solicited injection site reactions and systemic reactions [ Time Frame: Within 7 days after any injection ]
  Injection site reactions: pain, erythema, and swelling; Systemic reactions: fever, vomiting, crying abnormal, drowsiness, appetite lost, and irritability

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

Descriptive Information

• Brief Title: Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the Russian Federation and Mexico
• Official Title: Safety and Immunogenicity of a 3-Dose Schedule of an Investigational Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers

Brief Summary

Primary Objective:

1. To describe the vaccine seroprotection (antibody titer≥1:8) to the antigens (meningococcal serogroups A, C, Y, and W) present in MenACYW conjugate vaccine or Menveo® measured by serum bactericidal assay using human complement (hSBA), for Groups 1 and 2 when administered concomitantly with routine pediatric vaccines in healthy infants and toddlers in Mexico
2. To describe the vaccine seroprotection (antibody titer≥1:8) to the antigens (meningococcal serogroups A, C, Y, and W) present in MenACYW conjugate vaccine measured by hSBA, for Group 3, when administered concomitantly with routine pediatric vaccines in healthy infants and toddlers in the Russian Federation

Secondary Objective:

1. To describe hSBA vaccine seroresponse to the antigens (meningococcal serogroups A, C, Y, and W) 30 days after the last vaccination of the infant series, when administered concomitantly with routine pediatric vaccines in healthy infants and toddlers in Mexico and Russian Federation (RF)
2. To describe immunogenicity profile of routine pediatric vaccines when administered concomitantly with MenACYW conjugate vaccine or Menveo®; or when administered alone
3. To describe hSBA antibody responses against meningococcal serogroups A, C, Y, and W when MenACYW conjugate vaccine and Menveo® are administered concomitantly with routine pediatric vaccines in Mexico and RF
4. To describe antibody titers to the antigens present in MenACYW conjugate vaccine and Menveo®, before the first vaccination and 30 days after the last vaccination of the infant series and in the second year of life, when administered concomitantly with routine pediatric vaccines in a subset of subjects in Mexico and RF

• Detailed Description: Study duration per participant is approximately 12 months
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Healthy Volunteers (Meningococcal Infection)

Intervention

• Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine
  Pharmaceutical form: Liquid solution Route of administration : Intramuscular
• Biological: Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine
  Pharmaceutical form: Lyophilized powder combined with liquid component Route of administration : Intramuscular
  Other Name: Menveo®
• Biological: Measles, Mumps, and Rubella Virus Vaccine Live
  Pharmaceutical form: Lyophilized live virus vaccine Route of administration : Subcutaneous
• Biological: Pneumococcal 13-valent Conjugate Vaccine
  Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
  Other Name: Prevnar 13®
• Biological: Diphtheria, Tetanus, Pertussis (Acellular, Component) Poliomyelitis (inactivated) Vaccine, and Haemophilus influenza type b Conjugate Vaccine
  Pharmaceutical form: Powder and suspension for injection Route of administration: Intramuscular
  Other Name: Hexacima®
• Biological: Hepatitis B Vaccine
  Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
  Other Name: ENGERIX-B®
• Biological: Rotavirus Vaccine, Live, Pentavalent
  Pharmaceutical form: Oral solution Route of administration: Oral
  Other Name: RotaTeq®
• Biological: Diphtheria, tetanus, pertussis (acellular component), hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b conjugate vaccine
  Pharmaceutical form:Suspension for injection Route of administration: Intramuscular
  Other Name: Pentaxim®

Study Arms

• Experimental: Group 1 (Mexico)
  MenACYW conjugate vaccine at 2, 6, and 12 months of age + routine pediatric vaccines at 2, 4, 6, and 12 months of age
  Interventions:

  • Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine
  • Biological: Measles, Mumps, and Rubella Virus Vaccine Live
  • Biological: Pneumococcal 13-valent Conjugate Vaccine
  • Biological: Rotavirus Vaccine, Live, Pentavalent
  • Biological: Diphtheria, tetanus, pertussis (acellular component), hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b conjugate vaccine
• Active Comparator: Group 2 (Mexico)
  Menveo® at 2, 4, 6, and 12 months of age + routine pediatric vaccines at 2, 4, 6, and 12 months of age
  Interventions:

  • Biological: Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine
  • Biological: Measles, Mumps, and Rubella Virus Vaccine Live
  • Biological: Pneumococcal 13-valent Conjugate Vaccine
  • Biological: Rotavirus Vaccine, Live, Pentavalent
  • Biological: Diphtheria, tetanus, pertussis (acellular component), hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b conjugate vaccine
• Experimental: Group 3 (Russian Federation)
  MenACYW conjugate vaccine at 3, 6, and 12 months of age + routine pediatric vaccines at 2, 3, 4.5, 6, and 12 months of age
  Interventions:

  • Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine
  • Biological: Measles, Mumps, and Rubella Virus Vaccine Live
  • Biological: Pneumococcal 13-valent Conjugate Vaccine
  • Biological: Diphtheria, Tetanus, Pertussis (Acellular, Component) Poliomyelitis (inactivated) Vaccine, and Haemophilus influenza type b Conjugate Vaccine
  • Biological: Hepatitis B Vaccine
• Group 4 (Russian Federation)
  Routine pediatric vaccines at 2, 3, 4, 5, 6, and 12 months of age
  Interventions:

  • Biological: Measles, Mumps, and Rubella Virus Vaccine Live
  • Biological: Pneumococcal 13-valent Conjugate Vaccine
  • Biological: Diphtheria, Tetanus, Pertussis (Acellular, Component) Poliomyelitis (inactivated) Vaccine, and Haemophilus influenza type b Conjugate Vaccine
  • Biological: Hepatitis B Vaccine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 28, 2020): 525
• Original Estimated Enrollment (submitted: August 9, 2018): 825
• Actual Study Completion Date: February 18, 2022
• Actual Primary Completion Date: February 18, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria :

An individual must fulfill all of the following criteria in order to be eligible for trial enrollment:

• Infants 2 months of age (60 to 89 days of age) on the day of the first study visit.*
• Born after a full-term pregnancy, with an estimated gestation age ≥ 37 weeks and a birth weight ≥ 2.5 kg.
• Informed consent form has been signed and dated by the parent(s) or guardian(s), as required by local regulations.†
• Subject and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures.
• In good health as determined by medical history and physical assessment.

• For the Russian Federation: The subject's parents are able to verbally report or provide written documentation that the subject's mother was hepatitis B antigennegative during pregnancy with the subject.

  • "2 months" means from the 2nd month after birth to the day before the 3rd month after birth (2 months to 2 months 29 days); "60 days" means from the 60th day after birth to the day before the 90th day after birth (60 to 89 days).
  • In the Russian Federation, as per local regulations, only the subject's parent(s) are entitled to sign an informed consent form. A child under the responsibility of a guardian will not be included in the study

Exclusion criteria:

An individual fulfilling any of the following criteria is to be excluded from trial enrollment:

• 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 (ie, meningitis polysaccharide or meningitis conjugate vaccine containing serogroups A, C, Y, or W; or meningococcal B serogroup-containing vaccine).
• Previous vaccination against diphtheria, tetanus, pertussis, Haemophilus influenzae type b (Hib), poliovirus, rotavirus, Streptococcus pneumoniae, measles, mumps, rubella, and / or varicella.
• For Mexico: 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, Haemophilus influenzae type b, Streptococcus pneumoniae, and /or rotavirus infection / 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 traveling to countries with high endemic or epidemic disease)
• History of intussusception.
• History of any neurologic disorders, including seizures (febrile and non-febrile) 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 vaccines 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 of the first blood draw.
• 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.
• Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0 C*). 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.

  • For the Russian Federation, febrile illness is defined as temperature ≥ 37 C. A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided.

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: 2 Months to 12 Months (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Mexico, Russian Federation

Administrative Information

• NCT Number: NCT03630705
• Other Study ID Numbers: MET33; U1111-1183-6409 ( 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
• Product Manufactured in and Exported from the U.S.: Yes

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: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: March 2022