Safety and Immunogenicity of One Dose of Novartis' Meningococcal ACWY-CRM Vaccine and GlaxoSmithKline Biologicals' Meningococcal ACWY-TT Vaccine in Healthy Toddlers

Study Overview
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Brief Summary
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Evaluate the immune response and reactogenicity of one dose of Meningococcal ACWY-cross reactive material (CRM) and Meningococcal ACWY-tetanus toxoid (TT) in 12-15 months old healthy toddlers.

Official Title
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A Phase 2, Randomized, Controlled, Observer-Blind, Multi-Center Study Assessing the Safety and Immunogenicity of One Dose of Novartis' Meningococcal ACWY-CRM Vaccine and GlaxoSmithKline Biologicals' Meningococcal ACWY-TT Vaccine in Healthy Toddlers

Conditions
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Meningococcal Disease

Intervention / Treatment
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* Biological: MenACWY-CRM
* Biological: MenACWY-TT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children between 12 months and 15 months old inclusive who were born with an estimated gestational age ≥ 37 weeks. Parent(s)/legal guardian(s) had given written informed consent after the nature of the study had been explained according to local regulatory requirements. Parents/legal guardian available for all the visits and would comply with the requirements of the protocol (e.g., completion of the Diary Cards, availability for study visits / safety phone calls). In good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator. Exclusion Criteria: Previous confirmed or suspected disease caused by N. meningitidis. Previously exposed to clinically proven meningococcal disease or clinical bacterial meningitis without further microbiologic characterization, i.e. possible meningococcal disease. Previously immunized with a meningococcal vaccine or vaccine containing meningococcal antigen(s) (licensed or investigational). Received within 90 days prior to enrollment or were expected to receive during the study period any investigational or non-registered product (drug or vaccine). Received or planning to receive any vaccines within 14 days before and 30 days after administration of the study vaccine (Exceptions: Injectable influenza vaccine could be administered up to 14 days prior to study vaccination and at least 14 days after study vaccination). Major congenital defect or a serious chronic disease. History of any anaphylaxis, severe vaccine reactions, or allergy to any vaccine components including diphtheria toxoid (CRM197) or tetanus toxoid (TT) and latex. Required chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the study vaccination. (For corticosteroids, this means prednisone, or equivalent, ≥ 0.5 mg/kg/day. Inhaled and topical steroids were allowed). Receipt of immunoglobulins and/or any blood products within six months prior to study vaccination or who had administration planned during the study period. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Any bleeding disorder which was considered as a contraindication to intramuscular injection. Moderate or severe acute infection and/or fever (defined as temperature ≥ 38°C) within 3 days prior to enrollment. Systemic antibiotic treatment within 7 days prior to enrollment.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 15 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MenACWY-CRM<br>MenACWY-CRM | Biological: MenACWY-CRM<br>* MenACWY-CRM<br>|
| Active Comparator: MenACWY-TT<br>MenACWY-TT | Biological: MenACWY-TT<br>* MenACWY-TT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With at Least One Severe Solicited Adverse Event (AE) After Receiving One Dose of Either MenACWY-CRM Vaccine or MenACWY-TT. | Reactogenicity of MenACWY-CRM and comparator MenACWY-TT vaccine was assessed in subjects (12 to 15 months old) as measured by number of subjects with at least one severe solicited AE within 7 days after vaccination. Solicited AEs included tenderness, erythema, induration, irritability, sleepiness, change in eating habits, vomiting, diarrhea and fever. | Day 1 to Day 7 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With Human Serum Bactericidal Assay (hSBA) Titer ≥ 8 Against (N. Meningitidis) Serogroups A, C, W, and Y After Receiving One Dose of Either MenACWY-CRM Vaccine or MenACWY-TT Vaccine. | Immunogenicity of one dose of MenACWY-CRM and comparator MenACWY-TT vaccine was assessed in subjects (12 to 15 months old) as measured by the percentages of subjects with hSBA titer ≥ 8 directed against Neisseria meningitidis (N. meningitidis) serogroups A, C, W, and Y on Day 29 after vaccination. Persistence of immune responses was measured by the percentages of subjects with hSBA titer ≥ 8 on Day 180 post-vaccination. | Day 1, Day 29 and Day 180 post-vaccination | 
| Percentages of Subjects With Seroresponse Against N. Meningitidis Serogroups A, C, W, and Y After Receiving One Dose of Either MenACWY-CRM Vaccine or MenACWY-TT Vaccine. | Immunogenicity of one dose of MenACWY-CRM and comparator MenACWY-TT vaccine was assessed in subjects (12 to 15 months old) as measured by the percentages of subjects with seroresponse defined as for subjects with pre-vaccination hSBA titer < 4, post-vaccination hSBA titer ≥ 8; for subjects with pre-vaccination hSBA titer ≥ 4, an increase of at least four times the pre-vaccination hSBA directed against N. meningitidis serogroups A, C, W, and Y on Day 29 after vaccination. Persistence immune response was measured by the percentage of subjects with seroresponse at Day 180 after vaccination. | Day 29 and Day 180 post-vaccination | 
| hSBA Geometric Mean Titers (GMTs) Against N. Meningitidis Serogroups A, C, W, and Y After Receiving One Dose of Either MenACWY-CRM Vaccine or MenACWY-TT Vaccine. | Immunogenicity of one dose of MenACWY-CRM and comparator MenACWY-TT vaccine was assessed in subjects (12 to 15 months old) as measured by hSBA GMTs directed against N. meningitidis serogroups A, C, W, and Y on Day 29 after vaccination. Persistence of immune response was measured by hSBA GMTs at Day 180 after vaccination. | Day 1, Day 29 and Day 180 post-vaccination | 
| Percentages of Subjects With Rabbit Serum Bactericidal Assay (rSBA) Titer ≥ 8 Against Serogroups A, C, W, and Y After Receiving One Dose of Either MenACWY-CRM Vaccine or MenACWY-TT Vaccine. | Immunogenicity of one dose of MenACWY-CRM and comparator MenACWY-TT vaccine was assessed in subjects (12 to 15 months old) as measured by the percentages of subjects with rSBA titer ≥ 8 directed against N. meningitidis serogroups A, C, W, and Y on Day 29 after vaccination. Persistence of immune response was measured by percentages of subjects with rSBA titer ≥ 8 on Day 180 after vaccination. | Day 1, Day 29 and Day 180 post-vaccination | 
| Percentages of Subjects With rSBA Titer ≥ 128 Against Serogroups A, C, W, and Y After Receiving One Dose of Either MenACWY-CRM Vaccine or MenACWY-TT Vaccine. | Immunogenicity of one dose of MenACWY-CRM and comparator MenACWY-TT vaccine was assessed in subjects (12 to 15 months old) as measured by the percentages of subjects with rSBA titer ≥ 128 directed against N. meningitidis serogroups A, C, W, and Y on Day 29 after vaccination. Persistence of immune response was measured by percentages of subjects with rSBA titer ≥ 128 on Day 180 after vaccination. | Day 1, Day 29 and Day 180 post-vaccination | 
| Percentages of Subjects With Four-fold Increase in rSBA Titers Against Serogroups A, C, W, and Y After Receiving One Dose of Either MenACWY-CRM Vaccine or MenACWY-TT Vaccine. | Immunogenicity of one dose of MenACWY-CRM and comparator MenACWY-TT vaccine was assessed in subjects (12 to 15 months old) as measured by the percentages of subjects with four-fold increase in rSBA titer directed against N. meningitides serogroups A, C, W, and Y on Day 29 after vaccination. Persistence of immune response was measured by the percentages of subjects with four-fold increase in rSBA titer on Day 180 after vaccination. | Day 29 and Day 180 post-vaccination | 
| rSBA GMT Against N. Meningitidis Against Serogroups A, C, W, and Y After Receiving One Dose of Either MenACWY-CRM Vaccine or MenACWY-TT Vaccine. | Immunogenicity of one dose of MenACWY-CRM and comparator MenACWY-TT vaccine was assessed in subjects (12 to 15 months old) as measured by rSBA GMTs directed against N. meningitidis serogroups A, C, W, and Y on Day 29 after vaccination. Persistence of immune responses was measured by rSBA GMTs on Day 180. | Day 1, Day 29 and Day 180 post-vaccination | 
| Number of Subjects Reporting Solicited Adverse Events (AEs) After Receiving One Dose of Either MenACWY-CRM Vaccine or MenACWY-TT Vaccine. | Safety was assessed in terms of number of subjects (12 to 15 months old) reporting any and each of solicited local and systemic AEs reported from Day 1 to 7 after vaccination with one dose of either MenACWY-CRM or comparator MenACWY-TT vaccine. | Day 1 (6 hours) to Day 7 post-vaccination | 
| Number of Subjects Reporting Unsolicited (AEs) After Receiving One Dose of Either MenACWY-CRM Vaccine or MenACWY-TT Vaccine. | Safety was assessed in terms of number of subjects (12 to 15 months old) reporting unsolicited AEs (day 1 to day 29), SAEs, medically attended AEs, AEs leading to premature study withdrawal (Day 1 to Day 180) after vaccination with one dose of either MenACWY-CRM or comparator MenACWY-TT vaccine. | Day 1 to Day 29 or Day 1 to Day 180 post-vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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meningococcal disease, children, vaccination