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

Sanofi

Status and phase: Completed; Phase 2

Conditions: Meningococcal Infection; Meningitis

Treatments: Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein); Biological: Quadrivalent Meningococcal Polysaccharide (A, C, Y, and W-135) Tetanus Protein Conjugate; Biological: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein); Biological: Varicella Virus Vaccine Live; Biological: Rotavirus Vaccine; 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: Hepatitis B Vaccine; Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live

Study type: Interventional

Funder types: Industry

Identifiers

NCT01049035

UTN: U1111-1112-2593 (Other Identifier)

MET39

Details and patient eligibility

About

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.

Full 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.

Enrollment: 580 patients

Sex: All

Ages: 42 to 365 days old

Volunteers: Accepts Healthy Volunteers

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.).

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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580 participants in 7 patient groups

Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months

Experimental group

Description:

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.

Treatment:

Biological: Hepatitis B Vaccine

Biological: Rotavirus Vaccine

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: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Biological: Varicella Virus Vaccine Live

Biological: Quadrivalent Meningococcal Polysaccharide (A, C, Y, and W-135) Tetanus Protein Conjugate

Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live

Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months

Experimental group

Description:

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.

Treatment:

Biological: Hepatitis B Vaccine

Biological: Rotavirus Vaccine

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: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Biological: Varicella Virus Vaccine Live

Biological: Quadrivalent Meningococcal Polysaccharide (A, C, Y, and W-135) Tetanus Protein Conjugate

Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live

Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months

Experimental group

Description:

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.

Treatment:

Biological: Hepatitis B Vaccine

Biological: Rotavirus Vaccine

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: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Biological: Varicella Virus Vaccine Live

Biological: Quadrivalent Meningococcal Polysaccharide (A, C, Y, and W-135) Tetanus Protein Conjugate

Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live

Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months

Experimental group

Description:

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.

Treatment:

Biological: Hepatitis B Vaccine

Biological: Rotavirus Vaccine

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: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Biological: Varicella Virus Vaccine Live

Biological: Quadrivalent Meningococcal Polysaccharide (A, C, Y, and W-135) Tetanus Protein Conjugate

Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live

Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Group 5: MenACYW Conjugate Vaccine: Month 12

Experimental group

Description:

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.

Treatment:

Biological: Hepatitis B Vaccine

Biological: Rotavirus Vaccine

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: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Biological: Varicella Virus Vaccine Live

Biological: Quadrivalent Meningococcal Polysaccharide (A, C, Y, and W-135) Tetanus Protein Conjugate

Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live

Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Group 6: Control: 2, 4, 6, and 12 Months

Other group

Description:

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.

Treatment:

Biological: Hepatitis B Vaccine

Biological: Rotavirus Vaccine

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: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Biological: Varicella Virus Vaccine Live

Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live

Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Group 7: Control: 2, 4, 6, 12, and 15 Months

Other group

Description:

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.

Treatment:

Biological: Hepatitis B Vaccine

Biological: Rotavirus Vaccine

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: Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Biological: Varicella Virus Vaccine Live

Biological: M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live

Biological: Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein)