A Study of a Quadrivalent Meningococcal Tetanus Protein Conjugate Vaccine in Infants and Toddlers

Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine Administered in Infants and Toddlers

The purpose of this study was to evaluate the optimal vaccination schedule for a Quadrivalent Meningococcal Polysaccharide (A, C, Y and W-135) Tetanus Protein Conjugate Vaccine (MenACYW Conjugate vaccine) in order to provide an effective protein conjugate quadrivalent meningococcal vaccine in the population with the highest incidence of disease.

Objectives:

• To describe the safety profile of MenACYW Conjugate vaccine administered at 5 different schedules and concomitantly with routine pediatric vaccinations.
• To describe the immunogenicity profile of MenACYW Conjugate vaccine administered at 5 different schedules and concomitantly with routine pediatric vaccinations.
• To describe the immunogenicity profiles of selected licensed pediatric vaccines (Pentacel, Prevnar, M-M-RII, and Varivax) when administered either concomitantly with or without MenACYW Conjugate vaccine.

Study Overview

• Status: Completed
• Conditions: Meningitis; Meningococcal Infection
• Intervention / Treatment: Biological: Quadrivalent Meningococcal Polysaccharide (A, C, Y, and W-135) Tetanus Protein Conjugate; Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus B Conjugate (Tetanus Toxoid Conjugate) Vaccine Combined (DTaP-IPV/Hib combined); Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live; Biological: Varicella Virus Vaccine Live; Biological: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein); Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein); Biological: Rotavirus Vaccine; Biological: Hepatitis B Vaccine

Detailed Description

Participants received study vaccinations beginning at age 2, 6, 12, or 15 months, depending on the assigned schedule in their randomized groups. All participants underwent safety and immunogenicity assessments according to the schedule for their assigned group.

• Study Type: Interventional
• Enrollment (Actual): 580
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
    • Tuscaloosa, Alabama, United States, 35406
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
    • Little Rock, Arkansas, United States, 72205
  • California
    • Fountain Valley, California, United States, 92708
    • Huntington Beach, California, United States, 92647
  • Georgia
    • Marietta, Georgia, United States, 30062
    • Woodstock, Georgia, United States, 30189
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
    • Crestview Hills, Kentucky, United States, 41017
    • Louisville, Kentucky, United States, 40291
    • Louisville, Kentucky, United States, 40207
  • Louisiana
    • Bossier City, Louisiana, United States, 71111
  • North Carolina
    • Clyde, North Carolina, United States, 28721
  • Ohio
    • Cleveland, Ohio, United States, 44121
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15241
  • South Carolina
    • Barnwell, South Carolina, United States, 29812
  • Tennessee
    • Clarksville, Tennessee, United States, 37043
  • Texas
    • Fort Worth, Texas, United States, 76107
  • Utah
    • Layton, Utah, United States, 84041
    • Orem, Utah, United States, 84057
    • Springville, Utah, United States, 84663
  • Virginia
    • Midlothian, Virginia, United States, 23113
  • Washington
    • Spokane, Washington, United States, 99202
    • Spokane, Washington, United States, 99218

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 year (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Groups 1, 2, 3, 6, and 7: Aged 42 to 89 days on the day of inclusion; Group 4: Aged 6 months (180 days ± 14 days) on the day of inclusion; Group 5: Aged 12 months (365 days + 14 days) on the day of inclusion.
• Born at full term of pregnancy (greater than or equal to [≥] 37 weeks) and with a birth weight ≥2.5 kilogram (kg).
• Informed consent form had been signed and dated by the parent or other legally acceptable representative.
• Participant and parent/guardian were able to attend all scheduled visits and to be complied with all trial procedures.
• Group 4 only: Prior receipt of Pentacel and Prevnar at 2 and 4 months; 1 or 2 doses of rotavirus vaccine; and 2 or 3 previous doses of hepatitis B vaccine.

Group 5 only: Prior receipt of Pentacel and Prevnar at 2, 4, and 6 months; 2 or 3 doses of rotavirus vaccine; and 3 previous doses of hepatitis B vaccine.

Exclusion Criteria:

• Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the first trial vaccination.
• Planned participation in another clinical trial during the present trial period.
• Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
• Planned receipt of any vaccine in the 4 weeks following any trial vaccination, with the exception of influenza vaccine, which may be received 14 days before or after MenACYW Conjugate vaccine.
• Previous vaccination against meningococcal disease with either the trial vaccine or another vaccine.
• Receipt of blood or blood-derived products in the past 30 days, which might interfere with assessment of the immune response.
• 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).
• Known personal or maternal seropositivity for human immunodeficiency virus (HIV), hepatitis B vaccine, or hepatitis C, as reported by the parent/guardian.
• History of meningococcal infection, confirmed either clinically, serologically, or microbiologically.
• At high risk for meningococcal infection during the trial.
• 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.
• Thrombocytopenia, as reported by the parent/guardian.
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination.
• History of seizures.
• Personal or family history of Guillain-Barré Syndrome (GBS).
• Chronic illness that, in the opinion of the investigator, was at a stage where it might interfere with trial conduct or completion.

Temporary contraindications were resolved before vaccination:

• Febrile illness (temperature ≥38.0 degree Celsius [≥100.4 degree Fahrenheit]) or moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination.
• Group 5 only: Receipt of oral or injected antibiotic therapy within the 72 hours prior to the study blood draw. Topical antibiotics or antibiotic drops were not included in this exclusion criterion. (Note: This did not applied to the other groups at this time, as they did not have a blood draw within 30 days of the initial visit.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months; Participants aged 2 months (at the time of enrollment) received Quadrivalent Meningococcal Polysaccharide (A, C, Y, and W-135) Tetanus Protein (MenACYW) Conjugate vaccine at the age of Months 2, 4, 6, and a booster vaccination at the age of Month 12 along with Prevnar 7 or Prevnar 13 vaccine at the age of Months 2, 4, 6, and 12, Pentacel and Rotavirus vaccines at the age of Months 2, 4, and 6, Hepatitis-B vaccine at the age of Months 2 and 6, and M-M-RII and VARIVAX vaccines at the age of 12 months.	Biological: Quadrivalent Meningococcal Polysaccharide (A, C, Y, and W-135) Tetanus Protein Conjugate; 0.5 milliliter (mL), Intramuscular (IM) injection; Other Names: TetraMen-T; Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus B Conjugate (Tetanus Toxoid Conjugate) Vaccine Combined (DTaP-IPV/Hib combined); 0.5 mL, IM injection; Other Names: Pentacel; Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live; 0.5 mL, Subcutaneous (SC) injection; Biological: Varicella Virus Vaccine Live; 0.5 mL, SC injection; Other Names: Varivax; Biological: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein); 0.5 mL, IM injection; Other Names: Prevnar; Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein); 0.5 mL, IM injection; Other Names: Prevnar 13; Biological: Rotavirus Vaccine; oral; Other Names: RotaTeq/ROTARIX; Biological: Hepatitis B Vaccine; 0.5 mL, IM injection; Other Names: Engerix-B/Recombivax-HB
Experimental: Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months; Participants aged 2 months (at the time of enrollment) received MenACYW Conjugate vaccine at the age of Months 2, 4, 6, and a booster vaccination at the age of Month 15 along with Prevnar 7 or 13 vaccine at the age of Months 2, 4, 6, and 12, Rotavirus vaccine at the age of Months 2, 4, and 6, Hepatitis-B vaccine at the age of Months 2 and 6, M-M-RII and VARIVAX vaccines at the age of Month 12, and Pentacel vaccine at the age of Months 2, 4, 6, and 15.	Biological: Quadrivalent Meningococcal Polysaccharide (A, C, Y, and W-135) Tetanus Protein Conjugate; 0.5 milliliter (mL), Intramuscular (IM) injection; Other Names: TetraMen-T; Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus B Conjugate (Tetanus Toxoid Conjugate) Vaccine Combined (DTaP-IPV/Hib combined); 0.5 mL, IM injection; Other Names: Pentacel; Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live; 0.5 mL, Subcutaneous (SC) injection; Biological: Varicella Virus Vaccine Live; 0.5 mL, SC injection; Other Names: Varivax; Biological: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein); 0.5 mL, IM injection; Other Names: Prevnar; Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein); 0.5 mL, IM injection; Other Names: Prevnar 13; Biological: Rotavirus Vaccine; oral; Other Names: RotaTeq/ROTARIX; Biological: Hepatitis B Vaccine; 0.5 mL, IM injection; Other Names: Engerix-B/Recombivax-HB
Experimental: Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months; Participants aged 2 months (at the time of enrollment) received MenACYW Conjugate vaccine at the age of Months 2, 4 and a booster vaccination at the age of Month 12 along with Pentacel and Rotavirus vaccines at the age of Months 2, 4, and 6, Hepatitis-B vaccine at the age of Months 2 and 6, M-M-RII and VARIVAX vaccines at the age of Month 12, and Prevnar 7 or 13 vaccine at the age of Months 2, 4, 6, and 12.	Biological: Quadrivalent Meningococcal Polysaccharide (A, C, Y, and W-135) Tetanus Protein Conjugate; 0.5 milliliter (mL), Intramuscular (IM) injection; Other Names: TetraMen-T; Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus B Conjugate (Tetanus Toxoid Conjugate) Vaccine Combined (DTaP-IPV/Hib combined); 0.5 mL, IM injection; Other Names: Pentacel; Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live; 0.5 mL, Subcutaneous (SC) injection; Biological: Varicella Virus Vaccine Live; 0.5 mL, SC injection; Other Names: Varivax; Biological: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein); 0.5 mL, IM injection; Other Names: Prevnar; Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein); 0.5 mL, IM injection; Other Names: Prevnar 13; Biological: Rotavirus Vaccine; oral; Other Names: RotaTeq/ROTARIX; Biological: Hepatitis B Vaccine; 0.5 mL, IM injection; Other Names: Engerix-B/Recombivax-HB
Experimental: Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months; Participants aged 6 months (at the time of enrollment) received MenACYW Conjugate vaccine at the age of Month 6 along with Pentacel, Prevnar 7 or 13, Hepatitis-B and Rotavirus vaccines, and a booster vaccination of MenACYW at the age of Month 12 along with M-M-RII and VARIVAX vaccines. Before enrollment, participants were vaccinated with Pentacel, Prevnar, and Rotavirus vaccines at the age of Months 2 and 4, and Hepatitis-B vaccine at the age of Month 2.	Biological: Quadrivalent Meningococcal Polysaccharide (A, C, Y, and W-135) Tetanus Protein Conjugate; 0.5 milliliter (mL), Intramuscular (IM) injection; Other Names: TetraMen-T; Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus B Conjugate (Tetanus Toxoid Conjugate) Vaccine Combined (DTaP-IPV/Hib combined); 0.5 mL, IM injection; Other Names: Pentacel; Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live; 0.5 mL, Subcutaneous (SC) injection; Biological: Varicella Virus Vaccine Live; 0.5 mL, SC injection; Other Names: Varivax; Biological: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein); 0.5 mL, IM injection; Other Names: Prevnar; Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein); 0.5 mL, IM injection; Other Names: Prevnar 13; Biological: Rotavirus Vaccine; oral; Other Names: RotaTeq/ROTARIX; Biological: Hepatitis B Vaccine; 0.5 mL, IM injection; Other Names: Engerix-B/Recombivax-HB
Experimental: Group 5: MenACYW Conjugate Vaccine: Month 12; Participants aged 12 months (at the time of enrollment) received MenACYW Conjugate vaccine at the age of 12 months along with Prevnar 7 or 13, M-M-RII, and VARIVAX vaccines. Before enrollment, participants were vaccinated with Pentacel, Prevnar, and Rotavirus vaccines at the age of Months 2, 4, and 6, and Hepatitis-B vaccine at the age of Months 2 and 6.	Biological: Quadrivalent Meningococcal Polysaccharide (A, C, Y, and W-135) Tetanus Protein Conjugate; 0.5 milliliter (mL), Intramuscular (IM) injection; Other Names: TetraMen-T; Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus B Conjugate (Tetanus Toxoid Conjugate) Vaccine Combined (DTaP-IPV/Hib combined); 0.5 mL, IM injection; Other Names: Pentacel; Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live; 0.5 mL, Subcutaneous (SC) injection; Biological: Varicella Virus Vaccine Live; 0.5 mL, SC injection; Other Names: Varivax; Biological: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein); 0.5 mL, IM injection; Other Names: Prevnar; Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein); 0.5 mL, IM injection; Other Names: Prevnar 13; Biological: Rotavirus Vaccine; oral; Other Names: RotaTeq/ROTARIX; Biological: Hepatitis B Vaccine; 0.5 mL, IM injection; Other Names: Engerix-B/Recombivax-HB
Other: Group 6: Control: 2, 4, 6, and 12 Months; Participants aged 2 months (at the time of enrollment) received Pentacel and Rotavirus vaccines at the age of Months 2, 4, and 6, Hepatitis-B vaccine at the age of Months 2 and 6, Prevnar 7 or 13 vaccine at the age of Months 2, 4, 6, and 12 and M-M-RII and VARIVAX vaccines at the age of 12 months.	Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus B Conjugate (Tetanus Toxoid Conjugate) Vaccine Combined (DTaP-IPV/Hib combined); 0.5 mL, IM injection; Other Names: Pentacel; Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live; 0.5 mL, Subcutaneous (SC) injection; Biological: Varicella Virus Vaccine Live; 0.5 mL, SC injection; Other Names: Varivax; Biological: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein); 0.5 mL, IM injection; Other Names: Prevnar; Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein); 0.5 mL, IM injection; Other Names: Prevnar 13; Biological: Rotavirus Vaccine; oral; Other Names: RotaTeq/ROTARIX; Biological: Hepatitis B Vaccine; 0.5 mL, IM injection; Other Names: Engerix-B/Recombivax-HB
Other: Group 7: Control: 2, 4, 6, 12, and 15 Months; Participants aged 2 months (at the time of enrollment) received Rotavirus vaccine at the age of Months 2, 4, and 6, Hepatitis-B vaccine at the age of Months 2 and 6, Prevnar 7 or 13 vaccine at the age of Months 2, 4, 6, and 12, and M-M-RII and VARIVAX vaccines at the age of 12 months, and Pentacel vaccine at the age of Months 2, 4, 6, and 15.	Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus B Conjugate (Tetanus Toxoid Conjugate) Vaccine Combined (DTaP-IPV/Hib combined); 0.5 mL, IM injection; Other Names: Pentacel; Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live; 0.5 mL, Subcutaneous (SC) injection; Biological: Varicella Virus Vaccine Live; 0.5 mL, SC injection; Other Names: Varivax; Biological: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein); 0.5 mL, IM injection; Other Names: Prevnar; Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein); 0.5 mL, IM injection; Other Names: Prevnar 13; Biological: Rotavirus Vaccine; oral; Other Names: RotaTeq/ROTARIX; Biological: Hepatitis B Vaccine; 0.5 mL, IM injection; Other Names: Engerix-B/Recombivax-HB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an Serum Bactericidal Assay (SBA) Using Human Complement (SBA-HC) Titer Greater or Than Equal to (≥) 1:8 and ≥1:4: Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-protocol Population (PPP)	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. The PPP consisted of all participants included in the trial who received at least one dose of study or control vaccine, excluding those who did not meet all protocol-specified inclusion/exclusion criteria, did not receive the correct number of doses of the investigational vaccine, received a vaccine other than the one that he/she was randomized to receive, did not provide a post-dose serology sample in the proper time window, received a protocol-restricted therapy, medication or vaccine, was on systemic antibiotics within 3 days prior to study blood draw, had no serology sample or did not produce at least one valid test result, did not receive vaccine in the proper time window. Primary series PPP was defined as the PPP which was used for reporting data of time points prior to 12 months of age.	Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months
Percentage of Participants With an Serum Bactericidal Assay Using Human Complement Titer ≥1:8 and ≥1:4: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. PPP consisted of all participants included in the trial who received at least one dose of study or control vaccine, excluding those who did not meet all protocol-specified inclusion/exclusion criteria, did not received the correct number of doses of the investigational vaccine, received a vaccine other than the one that he/she was randomized to receive, did not provided a post-dose serology sample in the proper time window, received a protocol-restricted therapy, medication or vaccine, was on systemic antibiotics within 3 days prior to study blood draw, had no serology sample or did not produce at least one valid test result, did not receive vaccine in the proper time window. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.	Groups 1, 3, 4, and 6: at the age of 13 months; Groups 2 and 7: at the age of 16 months
Percentage of Participants With Serum Bactericidal Assay Using Human Complement Titer ≥1:8 and ≥1:4: Group 5 - Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. PPP consisted of all participants included in the trial who received at least one dose of study or control vaccine, excluding those who did not meet all protocol-specified inclusion/exclusion criteria, did not received the correct number of doses of the investigational vaccine, received a vaccine other than the one that he/she was randomized to receive, did not provided a post-dose serology sample in the proper time window, received a protocol-restricted therapy, medication or vaccine, was on systemic antibiotics within 3 days prior to study blood draw, had no serology sample or did not produce at least one valid test result, did not receive vaccine in the proper time window.	At the age of 13 months
Percentage of Participants With SBA-HC Pre-booster Titer ≥1:8 Who Then Achieved ≥4-Fold Rise in SBA-HC Titer After Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Pre-booster titer was defined as titer values reported before the age of 12 months. Percentage of participants whose pre-booster titer was ≥1:8 and achieved ≥4-fold rise in each meningococcal serogroups antibody titer (30-days post booster vaccination) were reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.	Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months); Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
Percentage of Participants With SBA-HC Pre-vaccination Titer ≥1:8 Who Then Achieved ≥4-fold Rise in SBA-HC Titer After Vaccination: Group 5 - Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Pre-vaccination titer was defined as titer values reported before the age of 12 months. Percentage of participants whose pre-vaccination titer was ≥1:8 and achieved ≥4-fold rise in each meningococcal serogroups antibody titer (30 days post-vaccination) were reported.	30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)
Percentage of Participants With SBA-HC Pre-booster Titer Less Than (<) 1:8 Who Then Achieved ≥4-Fold Rise in SBA-HC After Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Pre-booster titer was defined as titer values reported before the age of 12 months. Percentage of participants whose pre-booster titer was <1:8 and achieved ≥4-fold rise in each meningococcal serogroups antibody titer (30-days post booster vaccination) were reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.	Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months); Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
Percentage of Participants With SBA-HC Pre-Vaccination Titer <1:8 Who Then Achieved ≥4-Fold Rise in SBA-HC Titer After Vaccination: Group 5 - Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Percentage of participants with pre-vaccination titer <1:8 and achieved ≥4-fold rise in each meningococcal serogroups antibody titer (30-days post vaccination) were reported.	30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)
Serum Bactericidal Assay Using Human Complement Geometric Mean Titers (GMTs): Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Primary series PPP was defined as the PPP which was used for reporting data of time points prior to 12 months of age.	Groups 1, 2, 4, 6, and 7: at the age of 7 months, Group 3: at the age of 5 months
Serum Bactericidal Assay Using Human Complement Geometric Mean Titers: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.	Groups 1, 3, 4, and 6: at the age of 13 months; Groups 2 and 7: at the age of 16 months
Serum Bactericidal Assay Using Human Complement Geometric Mean Titers: Group 5 - Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC.	At the age of 13 months
Percentage of Participants With ≥4-fold Rise in SBA-HC Titer After the Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Percentage of participants with ≥4-fold rise in each meningococcal serogroups antibody titer (30 days post booster vaccination) were reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.	Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months), Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
Geometric Mean Fold Rise (GMFR) in SBA-HC Titer After the Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.	Groups 1, 3 and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months), Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
Percentage of Participants With a Serum Bactericidal Assay Using Baby Rabbit Complement (SBA-BR) Titer ≥1:8 and ≥1:128: Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Primary series PPP was defined as the PPP which was used for reporting data of time points prior to 12 months of age.	Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months
Percentage of Participants With SBA-BR Titer ≥1:8 and ≥1:128: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.	Groups 1, 3, 4, and 6: at the age of 13 months; Groups 2 and 7: at the age of 16 months
Percentage of Participants With SBA-BR Titer ≥1:8 and ≥1:128: Group 5 - Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR.	At the age of 13 months
Percentage of Participants With SBA-BR Pre-Booster Titer ≥1:8 Who Then Achieved ≥4-Fold Rise in SBA-BR Titer After Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Pre-booster titer was defined as titer value reported before the age of 12 months. Percentage of participants whose pre-booster titer was ≥1:8 and achieved ≥4-fold rise in each meningococcal serogroups antibody titer (30 days post booster vaccination) were reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.	Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months); Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
Percentage of Participants With SBA-BR Pre-Vaccination Titer ≥1:8 Who Then Achieved ≥4-Fold Rise in SBA-BR Titer After Vaccination: Group 5 - Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Percentage of participants whose pre-vaccination titer was ≥1:8 and achieved ≥4-fold rise in each meningococcal serogroups antibody titer at the age of Month 13 (i.e. 30-days post vaccination at Month 12) were reported.	30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)
Percentage of Participants With SBA-BR Pre-Booster Titer <1:8 Who Then Achieved ≥4-Fold Rise in SBA-BR Titers After Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Pre-booster titer was defined as titer value reported before the age of 12 months. Percentage of participants whose pre-booster titer was <1:8 and achieved ≥4-fold rise in each meningococcal serogroups antibody titer (30-days post booster vaccination) were reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.	Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months); Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
Percentage of Participants With SBA-BR Pre-Vaccination Titer <1:8 Who Then Achieved ≥4-Fold Rise in SBA-BR Titer After Vaccination: Group 5 - Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Pre-vaccination titer was defined as titer value reported before the age of 12 months. Percentage of participants with pre-vaccination titer <1:8 and who achieved ≥4-fold rise in each meningococcal serogroups antibody titer (30 days post-vaccination) were reported.	30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)
Percentage of Participants With ≥4-fold Rise in SBA-BR Titer After the Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Percentage of participants with ≥4-fold rise in each meningococcal serogroups antibody titer (30-days post booster vaccination) were reported. Booster PPP was defined as the PPP which was used for reporting data of time points at and after the age of 12 months.	Groups 1, 3, and 4: 30 days post booster vaccination (i.e., at the age of 13 months); Group 2: 30 days post booster vaccination (i.e., at the age of 16 months)
Serum Bactericidal Assay Using Baby Rabbit Complement Geometric Mean Titers: Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Primary series PPP was defined as the PPP which was used for reporting data of time points prior to 12 months of age.	Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months
Serum Bactericidal Assay Using Baby Rabbit Complement Geometric Mean Titers: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.	Groups 1, 3, 4, and 6: at the age of 13 months; Group 2 and 7: at the age of 16 months
Serum Bactericidal Assay Using Baby Rabbit Complement Geometric Mean Titers in Group 5: Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR.	At the age of 13 months
Geometric Mean Fold Rise in Serum Bactericidal Assay Using Baby Rabbit Complement Titer After the Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population	Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Percentage of participants with GMFR in each meningococcal serogroups antibody titer (30-days post booster vaccination) were reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.	Groups 1, 3, and 4: 30 days post booster vaccination at the age of 12 months (i.e., at the age of 13 months); Group 2: 30 days post booster vaccination at the age of 15 months (i.e. at the age of 16 months)
Antibody Titer/Concentration to All the Antigens Contained in Pentacel Vaccines: Groups 1, 2, 4, 6, and 7 - Primary Series Per-Protocol Population	Pentacel vaccine is Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine Combined (DTaP-IPV/Hib combined). Antibody titer to all antigens contained in pentacel vaccines (i.e., Anti-PRP, Anti-Diptheria, Anti-pertussis [pertussis toxoid [PT], pertactin [PRN], filamentous hemagglutinin [FHA], and fimbriae [FIM]], Anti-poliovirus [anti-poliovirus Type 1, Type 2 and Type 3] and anti-tetanus) were reported. Primary series PPP was defined as the PPP which was used for reporting data of time points prior to 12 months of age.	At the age of 7 months
Antibody Titer/Concentration to All Antigens Contained in Pentacel Vaccines: Groups 2 and 7 - Booster Per-Protocol Population	Pentacel vaccine is Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine Combined (DTaP-IPV/Hib combined). Antibody titer to all antigens contained in pentacel vaccines (i.e., Anti-PRP, Anti-Diptheria, Anti-pertussis [PT, PRN, FHA, and FIM], Anti-poliovirus [anti-poliovirus Type 1, Type 2, and Type 3], and Anti-tetanus) were reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.	At the age of 16 months
Percentage of Participants With Antibody Concentration ≥0.35 μg/mL for Serotypes in Prevnar 7 or 13 Vaccine: Groups 1, 2, 4, 6, and 7 - Primary Series Per-Protocol Population	Percentage of participants with anti-pneumococcal antibody concentrations ≥0.35 μg/mL for serotypes in Prevnar 7 or 13 vaccine i.e. 4, 6B, 9V, 14, 18C, 19F, and 23F is reported. Primary series PPP was defined as the PPP which was used for reporting data of time points prior to 12 months of age.	At the age of 7 months
Percentage of Participants With Antibody Concentration ≥0.35 μg/mL and ≥1.0 μg/mL for Serotypes in Prevnar 7 or 13 Vaccine: Groups 1, 3, 4, and 6 - Booster Series Per-Protocol Population	Percentage of participants with anti-pneumococcal antibody concentrations ≥0.35 μg/mL and ≥1.0 μg/mL for serotypes in Prevnar 7 or 13 vaccine i.e. 4, 6B, 9V, 14, 18C, 19F and 23F is reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.	At the age of 13 months
Percentage of Participants With Antibody Concentration ≥0.35 μg/mL and ≥1.0 μg/mL for Serotypes in Prevnar 7 or 13 Vaccine: Group 5- Per-Protocol Population	Percentage of participants with anti-pneumococcal antibody concentrations ≥0.35 μg/mL and ≥1.0 μg/mL for serotypes in Prevnar 7 or 13 vaccine i.e. 4, 6B, 9V, 14, 18C, 19F and 23F is reported.	At the age of 13 months
Percentage of Participants With Antibodies to All Antigens Contained in M-M-RII and VARIVAX Vaccines: Groups 1 and 6 - Booster Per-Protocol Population	Antibodies responses were measured by ELISA. Antigens contained in M-M-RII: Measles, Mumps, and Rubella and in Varivax®: Varicella. Percentage of participants with anti-measles, anti-mumps, anti-rubella, and anti-varicella antibody concentration that met the respective mentioned criterion were reported: Measles: ≥255 milli-International Units per milliliter (mIU/mL); Mumps: ≥10 Antibody units per milliliter (AbU/mL); Rubella: ≥10 International Units per milliliter (IU/mL); Varicella: ≥5 glycoprotein based enzyme-linked immunosorbent assay (gpELISA) unit/mL. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.	At the age of 13 months
Geometric Mean Concentrations (GMCs) of Antibody Titers to Tetanus Toxoid: Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population	Antibody concentrations against tetanus toxoid were measured by ELISA and expressed as GMC. Primary series PPP was defined as the PPP which was used for reporting data of time points prior to 12 months of age. Here, '0' in number analyzed field signifies none of the participants were evaluable at that specified time point because different groups had different planned data collection time points as defined in time frame and pre-specified in protocol.	Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months
Geometric Mean Concentrations of Antibodies to Tetanus Toxoid: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population	Antibody concentrations against tetanus toxoid were measured by ELISA and expressed as GMC. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months. Here, '0' in number analyzed field signifies none of the participants were evaluable at that specified time point because different groups had different planned data collection time points as defined in time frame and pre-specified in protocol.	Groups 1, 3, 4, and 6: at the age of 13 months, Group 2 and 7: at the age of 16 months
Geometric Mean Concentrations of Antibodies to Tetanus Toxoid: Group 5 - Per-Protocol Population	Antibody concentrations against tetanus toxoid were measured by ELISA and expressed as GMC.	At the age of 13 months
Number of Participants With Solicited Injection Site Reactions	Solicited injection site reactions: tenderness/pain, erythema, and swelling and were planned to be collected and reported for each vaccine separately and not planned to be collected for Rotavirus vaccine. Here, '0' in number analyzed field for MenACYW categories signifies no participant were evaluable because in Groups 6 and 7 MenACYW vaccine was not administered; for Group 5, '0' in number analyzed field signifies safety data collection was not planned for Pentacel and Hepatitis-B vaccines; for Groups 2 and 7, '0' in number analyzed field signifies safety data collection was not planned for M-M-RII and VARIVAX vaccines, as pre-specified.	Within 7 days post any vaccination
Number of Participants With Solicited Systemic Reactions	An solicited reaction (SR) was an adverse reaction (AR) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the electronic case report form (eCRF). Systemic AEs were all AEs that were not injection site reactions. They, therefore, include systemic manifestations as well as localized or topical manifestations that were not associated with the vaccination site. Solicited systemic reactions included Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability.	Within 7 days post any vaccination
Number of Participants With Unsolicited Adverse Events	An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of symptom and/or onset post-vaccination. These included both serious and non-serious events.	Within 30 days post any vaccination
Number of Participants With Immediate Unsolicited AE	An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of symptom and/or onset post-vaccination. These included both serious and non-serious events. Immediate Unsolicited AE were AEs reported within 30 minutes of vaccine administration.	Within 30 minutes post any vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Cornish MJ, Hedrick JA, Gabrielsen AA, Johnson AD, Miriam Pina L, Rehm C, Pan J, Neveu D, Da Costa X, Jordanov E, Dhingra MS. Safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) co-administered with routine pediatric vaccines in infants and toddlers: A Phase II study. Vaccine. 2022 Mar 1;40(10):1421-1438. doi: 10.1016/j.vaccine.2022.01.050. Epub 2022 Feb 7.

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2009
• Primary Completion (Actual): February 13, 2012
• Study Completion (Actual): February 13, 2012

Study Registration Dates

• First Submitted: January 13, 2010
• First Submitted That Met QC Criteria: January 13, 2010
• First Posted (Estimate): January 14, 2010

Study Record Updates

• Last Update Posted (Actual): March 28, 2022
• Last Update Submitted That Met QC Criteria: March 21, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Meningitis; Neisseria meningitidis; Meningococcal Infection; Tetravalent Meningococcal Vaccine
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Meningitis; Meningococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: MET39; UTN: U1111-1112-2593 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No