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: Recruiting
• First Posted: August 15, 2018
• Last Update Posted: February 16, 2021
• 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: February 16, 2021
• Actual Study Start Date: October 17, 2018
• Estimated Primary Completion Date: February 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 28, 2020)

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 versus [vs] 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: January 28, 2020)

• Antibody titers against meningococcal serogroups A, C, Y, and W after infant series vaccination [ Time Frame: Before the first vaccination and 30 days after the last vaccination of the infant series (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 with MenACYW conjugate vaccine or Menveo® (Dose 2 of MenACYW conjugate vaccine and Dose 3 of Menveo®) in Mexico (Group 1 vs Group 2)
  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 with MenACYW conjugate
• 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

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 antibody titers 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 antibody titers 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 the hSBA vaccine seroresponse to the antigens (meningococcal serogroups A, C, Y, and W) for Groups 1 and 2, 30 days after the last vaccination of the infant series (Dose 2 of MenACYW conjugate vaccine and Dose 3 of Menveo®), when administered concomitantly with routine pediatric vaccines in healthy infants and toddlers in Mexico
2. To describe the hSBA vaccine seroresponse to the antigens (meningococcal serogroups A, C, Y, and W) for Group 3, 30 days after the last vaccination of the infant series (Dose 2 of MenACYW conjugate vaccine), when administered concomitantly with routine pediatric vaccines in healthy infants and toddlers in the Russian Federation

• 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: Subcutaneous
• 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: Subcutaneous
• Biological: Hepatitis B Vaccine
  Pharmaceutical form: Suspension for injection Route of administration: Subcutaneous
• Biological: Rotavirus Vaccine, Live, Pentavalent
  Pharmaceutical form: Oral solution Route of administration: Oral
• 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

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: Recruiting
• Estimated Enrollment (submitted: January 28, 2020): 525
• Original Estimated Enrollment (submitted: August 9, 2018): 825
• Estimated Study Completion Date: February 2022
• Estimated Primary Completion Date: February 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: Trial Transparency email recommended (Toll free number for US & Canada); 800-633-1610 ext 1 then #; RegistryContactUS@sanofipasteur.com

• Listed Location Countries: Mexico, Russian Federation

Administrative Information

• NCT Number: NCT03630705
• Other Study ID Numbers: MET33; U1111-1183-6409 ( Other Identifier: UTN )
• 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://www.clinicalstudydatarequest.com/

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

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi Pasteur, a Sanofi Company

• PRS Account: Sanofi
• Verification Date: February 2021