Immunogenicity and Safety of MenACWY in Infants (6 & 12 Months)

Study Overview
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Brief Summary
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To assess the immunogenicity of Novartis (formerly Chiron) Meningococcal ACWY conjugate vaccine (MenACWY) when administered as a two-dose schedule at 6 and 12 months of age.

Official Title
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A Phase 2, Partially Randomized, Open Label, Multicenter Study to Evaluate the Safety and Immunogenicity After One or Two Doses of Novartis (Formerly Chiron) Meningococcal ACWY Conjugate Vaccine Administered to Healthy Infants and Young Children

Conditions
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Meningococcal Meningitis

Intervention / Treatment
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* Biological: MenACWY-CRM
* Biological: MenC-CRM
* Biological: DTaP-Hib-IPV
* Biological: PC7
* Biological: MMR
* Biological: Varicella


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria for Groups I (MenACWY-CRM_6-12 M) and II (MenACWY-CRM_12 M) Subjects eligible for enrollment in the study were healthy infants: who were 6 months old and who were born after full-term pregnancy with an estimated gestational age of 37 weeks or greater and a birth weight 2.5 kg or greater; who previously received two doses of PC7 and DTaP-Hib-IPV vaccines; for whom a parent/legal guardian gave written informed consent, after the nature of the study was explained; who were available for all the visits scheduled in the study; who were in good health as determined by medical history, physical examination, and clinical judgment of the investigator. Inclusion criteria for Group III (MenC-CRM_12 M_MenACWY-CRM_18 M) Subjects eligible for enrollment in the study were healthy infants: who were 12 months old; who previously received three doses of DTaP-Hib-IPV (Pentacel) vaccines; for whom a parent/legal guardian gave written informed consent, after the nature of the study was explained; who were available for all the visits scheduled in the study; who were in good health as determined by medical history, physical examination, and clinical judgment of the investigator. Exclusion criteria: Subjects were not to be included in this study if: their parents/legal guardians were unwilling or unable to give written informed consent to participate in the study; they previously received any meningococcal vaccine; they had a previously ascertained or suspected disease caused by Neisseria meningitidis (N meningitidis); they had a history of any anaphylactic shock, asthma, urticaria, or other allergic reaction after previous vaccinations or known hypersensitivity to any vaccine component; they had experienced significant acute or chronic infection within the previous 7 days or had experienced fever (38.0ºC or greater) within the previous 3 days; they had any present or suspected serious acute disease (e.g., leukemia, lymphomas), or chronic disease (e.g., with signs of cardiac failure, renal failure, severe malnutrition, or insulin-dependent diabetes), or progressive neurological disease, or a genetic anomaly/known cytogenic disorders (e.g., Down's syndrome), or who had a diagnosed cardiac defect or abnormality of hemodynamic significance (e.g., ventricular septal defect, patent ductus arteriosus, or atrial septal defect); they had a known or suspected autoimmune disease or impairment /alteration of immune function resulting from use of (for example): any immunosuppressive therapy since birth; immunostimulants since birth; any systemic corticosteroid administered for more than 5 days or in a daily dose of greater than 1 mg/kg/day prednisone or equivalent for 5 days or less in the previous 30 days; they had a suspected or known HIV infection or HIV-related disease; they had received parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within the past 90 days and were expected to receive it for the full length of the study; they had a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time; they had a history of seizure disorder: febrile seizure; any other seizure disorder; they had taken systemic antibiotics (either oral or parenteral) within the previous 14 days (EXCEPTION: subjects who had received an oral or parenteral β-lactam antibiotic [e.g.: penicillin, amoxicillin, ceftriaxone, cefuroxime or cephalexin] could have been enrolled 7 days following the last dose); their parents/legal guardians were planning to leave the area of the study center before the end of the study period; they had any condition which, in the opinion of the investigator, might have interfered with the evaluation of the study objectives.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 12 Months

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: MenACWY-CRM_6-12 M<br>Subjects received 2 doses of MenACWY-CRM (1 dose at 6 and 12 months of age). Subjects also received routine vaccines: 2 doses of PC7 (1 dose at 6 and 12 months of age), 1 dose of DTaP-Hib-IPV (at 6 months of age) and 1 dose of MMR+Varicella (at 13 months of age) | Biological: MenACWY-CRM<br>* Subjects received the full dose (0.5 mL) of MenACWY-CRM, obtained by extemporaneous mixing of lyophilized MenA powder component and the MenCWY suspension, administered by IM injection into the anterolateral area of the right thigh.<br>* Other names: Meningococcal ACWY conjugate vaccine;Biological: DTaP-Hib-IPV<br> <br> * Other names: Combined vaccine containing diphtheria, tetanus, pertussis, Haemophilus influenzae type B and inactivated polio virus; Pentacel;Biological: PC7<br>* One dose (0.5 mL) of PC7, supplied in pre-filled syringe, administered by IM injection into the anterolateral area of the left thigh.<br>* Other names: Heptavalent conjugate pneumococcal; Prevnar;Biological: MMR<br> <br> * Other names: Measles, mumps and rubella;Biological: Varicella<br> <br> |
| Experimental: MenACWY-CRM_12 M<br>Subjects received 1 dose of MenACWY-CRM at 12 months of age. Subjects also received routine vaccines: 2 doses of PC7 (1 dose at 6 and 12 months of age), 1 dose of DTaP-Hib-IPV (at 6 months of age) and 1 dose of MMR+Varicella (at 13 months of age) | Biological: MenACWY-CRM<br>* Subjects received the full dose (0.5 mL) of MenACWY-CRM, obtained by extemporaneous mixing of lyophilized MenA powder component and the MenCWY suspension, administered by IM injection into the anterolateral area of the right thigh.<br>* Other names: Meningococcal ACWY conjugate vaccine;Biological: DTaP-Hib-IPV<br> <br> * Other names: Combined vaccine containing diphtheria, tetanus, pertussis, Haemophilus influenzae type B and inactivated polio virus; Pentacel;Biological: PC7<br>* One dose (0.5 mL) of PC7, supplied in pre-filled syringe, administered by IM injection into the anterolateral area of the left thigh.<br>* Other names: Heptavalent conjugate pneumococcal; Prevnar;Biological: MMR<br> <br> * Other names: Measles, mumps and rubella;Biological: Varicella<br> <br> |
| Experimental: MenC-CRM_12 M_MenACWY-CRM_18 M<br>Subjects received 1 dose of MenC-CRM (at 12 months of age) and 1 dose of MenACWY-CRM (at 18 months of age). Subjects also received routine vaccines: 1 dose of PCV7 (at 12 months), MMR+Varicella (at 13 months) and DTaP-Hib-IPV (at 18 months) | Biological: MenACWY-CRM<br>* Subjects received the full dose (0.5 mL) of MenACWY-CRM, obtained by extemporaneous mixing of lyophilized MenA powder component and the MenCWY suspension, administered by IM injection into the anterolateral area of the right thigh.<br>* Other names: Meningococcal ACWY conjugate vaccine;Biological: MenC-CRM<br>* One dose (0.5 mL) of MenC-CRM was obtained by extemporaneous mixing just before injection of the lyophilized MenC component and a saline solvent, administered by IM injection into the arm region.<br>* Other names: Meningococcal C conjugate vaccine;Biological: DTaP-Hib-IPV<br> <br> * Other names: Combined vaccine containing diphtheria, tetanus, pertussis, Haemophilus influenzae type B and inactivated polio virus; Pentacel;Biological: PC7<br>* One dose (0.5 mL) of PC7, supplied in pre-filled syringe, administered by IM injection into the anterolateral area of the left thigh.<br>* Other names: Heptavalent conjugate pneumococcal; Prevnar;Biological: MMR<br> <br> * Other names: Measles, mumps and rubella;Biological: Varicella<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With hSBA Titers ≥1:4 Against Each of 4 Meningococcal Serogroups After MenACWY-CRM Vaccination Administered as 2-Dose or 1-Dose Schedule | Immunogenicity was measured as the percentage of subjects with hSBA titers ≥1:4 against meningococcal serogroups A, C, W and Y, evaluated by serum bactericidal assay using human complement (hSBA), before vaccination and 1 month after 2-dose schedule of MenACWY-CRM administered at 6 and 12 months of age (MenACWY-CRM_6-12 M group) or 1-dose schedule administered at 12 months (MenACWY-CRM_12 M group) | Before and 1 month after 2-dose or 1-dose schedule | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean hSBA Titers Against Each of 4 Meningococcal Serogroups After MenACWY-CRM Vaccination Administered as 2-Dose or 1-Dose Schedule | The immune response was measured as the hSBA geometric mean titers (GMTs) against meningococcal serogroups A, C, W and Y, before vaccination and 1 month after 2-dose schedule of MenACWY-CRM administered at 6 and 12 months of age (MenACWY-CRM_6-12 M group) or 1-dose schedule administered at 12 months of age (MenACWY-CRM_12 M group) | Before and 1 month after 2-dose or 1-dose schedule | 
| Percentage of Subjects With hSBA Titers ≥1:8 Against Each of 4 Meningococcal Serogroups After MenACWY-CRM Vaccination Administered as 2-Dose or 1-Dose Schedule | Immunogenicity was measured as the percentage of subjects with hSBA titers ≥1:8 against meningococcal serogroups A, C, W and Y, before vaccination and 1 month after 2-dose schedule of MenACWY-CRM administered at 6 and 12 months of age (MenACWY-CRM_6-12 M group) or 1-dose schedule administered at 12 months of age (MenACWY-CRM_12 M) | Before and 1 month after 2-dose or 1-dose schedule | 
| Percentage of Subjects With hSBA Titers ≥1:4 or ≥1:8 Against Meningococcal Serogroup C After One Vaccination of MenC-CRM Administered at 12 Months of Age | Immunogenicity was measured as the percentage of subjects who achieved hSBA titers ≥1:4 or ≥1:8 against meningococcal serogroup C, before and 1 month after one vaccination of MenC-CRM administered concomitantly with Prevnar at 12 months of age | Before and 1 month after MenC-CRM vaccination at 12 months | 
| Geometric Mean hSBA Titers Against Meningococcal Serogroup C After One Vaccination of MenC-CRM Administered at 12 Months of Age | The immune response was measured as the hSBA GMT against meningococcal serogroup C, before and 1 month after one vaccination of MenC-CRM administered concomitantly with Prevnar at 12 months of age | Before and 1 month after MenC-CRM vaccination at 12 months | 
| Percentage of Subjects With hSBA Titers ≥1:4 or ≥1:8 Against Meningococcal Serogroup A, W and Y After One Vaccination of MenACWY-CRM Administered at 18 Months of Age | Immunogenicity was measured as the percentage of subjects who achieved hSBA titers ≥1:4 or ≥1:8 against meningococcal serogroups A, W and Y, before and 1 month after one vaccination of MenACWY-CRM administered concomitantly with Pentacel at 18 months of age | Before and 1 month after MenACWY-CRM vaccination at 18 months | 
| hSBA GMTs Against Meningococcal Serogroups A, W and Y After One Vaccination of MenACWY-CRM Administered at 18 Months of Age | The immune response was measured as the hSBA GMTs against meningococcal serogroups A, W and Y, before and 1 month after one vaccination of MenACWY-CRM administered concomitantly with Pentacel at 18 months of age | Before and 1 month after MenACWY-CRM vaccination at 18 months | 
| Percentage of Subjects With hSBA Titers ≥1:4 or ≥1:8 Against Meningococcal Serogroup C After MenACWY-CRM Vaccination Administered at 18 Months of Age, Following One Vaccination of MenC-CRM at 12 Months of Age | Booster response was measured as the percentage of subjects who achieved hSBA titers ≥1:4 or ≥1:8 against meningococcal serogroup C, before and 1 month after MenACWY-CRM vaccination administered at 18 months of age, following one vaccination of MenC-CRM at 12 months of age | Before and 1 month after MenACWY-CRM vaccination at 18 months | 
| hSBA GMT Against Meningococcal Serogroup C After MenACWY-CRM Vaccination Administered at 18 Months of Age, Following One Vaccination of MenC-CRM at 12 Months of Age | Booster response was measured as the hSBA GMT against meningococcal serogroup C, before and 1 month after MenACWY-CRM vaccination administered at 18 months of age, following one vaccination of MenC-CRM at 12 months of age | Before and 1 month after MenACWY-CRM vaccination at 18 months | 
| Number of Subjects Who Reported Solicited Local and Systemic Reactions After Any MenACWY-CRM, MenC-CRM and Concomitant Vaccination | The safety was assessed as the number of subjects who reported solicited local and systemic reactions from day 1 through day 7 following any vaccination of MenACWY-CRM, MenC-CRM and concomitant vaccination | From day 1 through day 7 after any vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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meningitis, children, vaccine