Safety and Immunogenicity of 2 or 3 Doses of MenACWY Conjugate Vaccine in Healthy Infants and the Effects of a Booster Dose of MenACWY Administered in the Second Year of Life

Study Overview
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Brief Summary
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The purpose of this study was to assess immunogenicity of a 3-dose versus 4-dose infant vaccination schedule including kinetics of immune response in the early phases of the series.

Official Title
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A Phase 3b, Randomized, Open-Label, Multi-Center Study to Evaluate the Safety and Immunogenicity of 2 or 3 Doses of MenACWY Conjugate Vaccine in Healthy Infants and the Effects of a Booster Dose of MenACWY Administered in the Second Year of Life.

Conditions
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Meningococcal Disease, Meningococcal Meningitis

Intervention / Treatment
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* Biological: MenACWY-CRM
* Biological: MenACWY-CRM
* Biological: Routine Vaccines


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants of both genders who are in generally good health will be eligible for this study. For infants to be enrolled, the parents/legal representatives need to provide written informed consent and to be available for all study visits. Exclusion Criteria: Serious, acute, or chronic illnesses are reasons for exclusion.

Ages Eligible for Study
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Minimum Age: 55 Days
Maximum Age: 89 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MenACWY3<br>Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age. | Biological: MenACWY-CRM<br>* This group received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.<br>Biological: Routine Vaccines<br>* Each 0.5 mL dose of the pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein) is formulated to contain approximately 2.2 μg of each of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F saccharides.<br>|
| Experimental: MenACWY4<br>All the subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4. | Biological: MenACWY-CRM<br>* This group received a 3-dose primary series at 2, 4, and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.<br>Biological: Routine Vaccines<br>* Each 0.5 mL dose of the pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein) is formulated to contain approximately 2.2 μg of each of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F saccharides.<br>|
| Placebo Comparator: Routine Vaccines<br>Subjects received routine vaccines only, including PCV-13, at 2, 4 and 6 months of age and a toddler dose at 12 months of age. | Biological: Routine Vaccines<br>* Each 0.5 mL dose of the pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein) is formulated to contain approximately 2.2 μg of each of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F saccharides.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Serum Bactericidal Activity Using Human Complement (hSBA) ≥ 1:8 Against N. Meningitidis Serogroups A, C, W and Y Following a 4-dose Schedule of Men ACWY Vaccination. | The immune response was assessed in terms of percentage of subjects with hSBA ≥ 1:8 against N. meningitidis serogroups A, C, W and Y following 4 doses of Men ACWY vaccine given to infants at 2, 4, 6 and 12 months of age. | 13 months of age | 
| Percentage of Subjects With hSBA ≥ 1:8 Against N. Meningitidis Serogroups A, C, W and Y Following 4-Dose and 3-Dose Schedule of Men ACWY Vaccination. | The immune response was assessed in terms of percentage of subjects with hSBA ≥ 1:8 against N. meningitidis serogroups A, C, W and Y following 4 doses of Men ACWY vaccine given to infants at 2, 4,6 and 12 months of age and 3 doses of Men ACWY given to infants at 2, 4 and 12 months of age. | 13 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With hSBA ≥1:8 Against N. Meningitidis Serogroups A, C, W and Y at Baseline (2 Months of Age) and at 3, 4, 5, and 7 Months of Age. | Antibody levels were assessed in terms of percentage of subjects with hSBA ≥ 1:8 against N. meningitidis serogroups A, C, W and Y at baseline (2 months of age) and at 3, 4, 5 and 7 months of age. | Baseline (2 months of age), 3 months, 4 months , 5 months and 7 months of age | 
| Geometric Mean hSBA Titers Against N Meningitis Serogroups A, C, W and Y at Baseline (2 Months of Age) and at 3, 4, 5, and 7 Months of Age. | Antibody levels were assessed in terms of geometric mean titers (GMTs) against N. meningitidis serogroups A, C, W and Y at baseline (2 Months of Age) and at 3, 4, 5, and 7 Months of Age. | Baseline(2 months of age), 3 months, 4 months , 5 months and 7 months of age. | 
| Percentage of Subjects With hSBA ≥1:8 Following 2 and 3 Infant Doses of MenACWY. | Percentage of subjects with hSBA ≥1:8 against N meningitis serogroups A, C, W and Y was assessed following 2 and 3 infant doses of MenACWY as measured prior to the toddler dose at 12 months of age. | 12 months of age. | 
| Geometric Mean hSBA Titers Following 2 and 3 Infant Doses of MenACWY. | The immune response was assessed in terms of GMTs against N. meningitidis serogroups A, C, W and Y following 2 and 3 infant doses of MenACWY as measured prior to the toddler dose at 12 months of age. | 12 months of age | 
| GMTs at 13 Months of Age After Completion of 3- and 4-Dose Series of MenACWY. | Immune response was assessed in terms of GMTs against N meningitis serogroups A, C, W and Y at 1 month after completion of a 3- and 4- dose series of MenACWY. | 13 months of age | 
| Percentage of Subjects With 4-fold Increase in hSBA Titers Against N Meningitis Serogroups A, C, W and Y Between 12 and 13 Months of Age. | The immune response was assessed in terms of percentage of subjects with 4-fold increase in hSBA titers between post and pre toddler dose against N meningitis serogroups A, C, W and Y, 1 month after completing a 3- or 4-dose series of MenACWY. | 13 months of age | 
| Effect of Concomitant Administration of 2 or 3 Doses of MenACWY on Immune Response to PCV-13 Antigens at 7 Months of Age. | Percentage of subjects with IgG concentration ≥ 0.35 μg/mL against pneumococcal conjugate vaccine (PCV-13) antigens at 7 Months of age following concomitant administration of 2 or 3 doses of MenACWY with PCV-13. | 7 months of age. | 
| Effect of Concomitant Administration of 3 or 4 Doses of MenACWY on Immune Response to PCV-13 Antigens at 13 Months of Age. | Geometric mean concentrations (GMCs) of antibodies against PCV-13 vaccine antigens at 13 months of age following concomitant administration of a 3- or 4-dose series of MenACWY with PCV-13. | 13 months of age. | 
| Percentage Of Subjects Reporting at Least One Severe Systemic Solicited Adverse Event. | Safety was assessed as the percentages of subjects who reported severe solicited systemic adverse events within 30 minutes through day 7 of MenACWY administration with concomitant vaccines vs. concomitant vaccines alone. | Within 7 days | 
| Number Of Subjects Reporting Solicited Local or Systemic Adverse Events. | Safety was assessed as the number of subjects who reported solicited local or systemic adverse events between 6 hours and day 7 after administration of MenACWY with concomitant vaccines vs. concomitant vaccines alone. | Day 1 through Day 7 | 
| Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination. |  | 13 months of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningococcal, ACWY, Conjugate Vaccine, Meningitis, Infants, Persistence