Safety and Immune Response of Novartis MenACWY-CRM Conjugate Vaccine When Given to Healthy Toddlers

Study Overview
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Brief Summary
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Safety immune response of Novartis MenACWY-CRM conjugate vaccine when given to healthy toddlers

Official Title
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A Phase 3, Open-Label, Randomized, Multi-Center Study to Evaluate the Safety and Immunogenicity of MMRV Vaccine When Administered Concomitantly With Novartis Meningococcal ACWY Conjugate Vaccine to Healthy Toddlers

Conditions
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Meningococcal Infections

Intervention / Treatment
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* Biological: MenACWY-CRM + MMRV
* Biological: MMRV
* Biological: MenACWY-CRM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: who are healthy 7 to 9 months old or 12 months old (inclusive plus 14 days) and for whom, after the nature of the study has been explained, the parent or legal guardian has provided written informed consent; who have received complete primary vaccination with recommended licensed vaccines; who are available for all visits and telephone calls scheduled for the study; Exclusion Criteria: whose parent or legal guardian is unwilling or unable to give written informed assent consent who had a previous or suspected disease caused by N. meningitidis; who had previous or suspected infection with measles, mumps, rubella, varicella, and/or herpes zoster; who had household contact with and/or intimate exposure to an individual with culture-proven N. meningitidis infection within 60 days prior to enrollment; who had household contact with and/or intimate exposure to an individual with measles, mumps, rubella and/or varicella infection within 60 days prior to enrollment; who have previously been immunized with a meningococcal vaccine or vaccine containing meningococcal antigen(s) who have previously received any measles, mumps, rubella or varicella vaccine either alone or in any combination; who have received any investigational agents or vaccines within 90 days prior to enrollment or who expect to receive an investigational agent or vaccine prior to the completion of the study; who have any serious acute, chronic or progressive disease such as, cancer, diabetes, heart failure, malnutrition, epilepsy, HIV/AIDS, Guillain Barre Syndrome who have a history of anaphylaxis, serious vaccine reactions or allergy to any part of the vaccine, who have a known or suspected impairment/alteration of immune function, either congenital or acquired who have Down's syndrome or other known cytogenic disorders; bleeding diathesis

Ages Eligible for Study
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Minimum Age: 7 Months
Maximum Age: 1 Year

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MenACWY-CRM+ MMRV<br> | Biological: MenACWY-CRM + MMRV<br>* One injection of MenACWY-CRM vaccine at 7-9 months of age; the second injection of MenACWY-CRM vaccine concomitantly administered with MMRV (Measles, Mumps, Rubella and Varicella) vaccine at 12 months of age.<br>|
| Active Comparator: MMRV<br> | Biological: MMRV<br>* one injection of MMRV (Measles, Mumps, Rubella and Varicella) vaccine at 12 months of age<br>|
| Experimental: MenACWY-CRM<br> | Biological: MenACWY-CRM<br>* Two injections of MenACWY-CRM at 7-9 months and 12 months of age; one injection of MMRV (Measles, Mumps, Rubella and Varicella) at 13.5 months of age<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With a Seroresponse to Measles, Mumps, Rubella and Varicella Following Concomitant Administration of MMRV Vaccine With MenACWY-CRM Vaccine | Percentages of subjects with seroresponses to measles, mumps, rubella and varicella after one dose of MMRV vaccine (at 12 months) when given concomitantly with MenACWY-CRM vaccine compared to when MMRV vaccine was given alone, are reported. Seroresponse was defined as the percentage of initially seronegative subjects who show seroconversion to measles (≥255 mIU/mL), mumps (≥10 ELISA Ab units), rubella (≥10 IU/mL) and the percentage of initially seronegative subjects who show seroprotection (≥5 gp ELISA units/mL) for varicella. Immunogenicity to measles, mumps, rubella and varicella at 6 weeks after vaccination with one dose of MMRV given concomitantly with MenACWY-CRM was considered non-inferior to immunogenicity of MMRV administered alone if the lower limit of two-sided 95% CI of the difference in the percentage of subjects with seroconversion for measles, mumps, and rubella, and seroprotection for varicella was greater than -5% (measles, mumps and rubella) and -10% (varicella). | 6 weeks post vaccination | 
| Percentages of Subjects With Serum Bactericidal Titers ≥1:8 Following Concomitant Administration of MenACWY-CRM Vaccine With MMRV Vaccine. | Percentages of subjects with hSBA ≥1:8, against N.meningitidis serogroups A, C, W-135, and Y following two doses of MenACWY-CRM vaccine (at 7-9 months and 12 months) when concomitantly administered with MMRV vaccine (12 months) compared to when MenACWY-CRM vaccine was given alone, are reported. The serum bactericidal antibodies directed against N.meningitidis serogroups A, C, W-135, and Y, were measured by human complement Serum Bactericidal Assay (hSBA). The immune response of MenACWY-CRM given concomitantly with MMRV was considered non-inferior to the immunogenicity of MenACWY-CRM administered alone if the lower limit of the two-sided 95% CI around the difference of the percentage of subjects with hSBA ≥1:8 at 6 weeks after the second dose of MenACWY-CRM given to 12-month old toddlers {P MMRV+MenACWY minus P MenACWY} was greater than -10% for each serogroup. | 6 weeks post second dose | 
| Percentages of Subjects With hSBA ≥1:8 Following Two Doses of MenACWY-CRM Vaccine | The antibody response following two doses of MenACWY-CRM vaccine (at 7-9 months and 12 months) was considered adequate if the lower limit of the two-sided 95% CI for the percentage of subjects with hSBA ≥1:8, at 6 weeks following the second dose of MenACWY-CRM, was greater than 85% for serogroups C, W-135, or Y and greater than 65% for serogroup A. | 6 weeks post vaccine dose 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With hSBA ≥1:4 After Two Doses of MenACWY-CRM Vaccine | The percentages of subjects with hSBA ≥1:4 directed against N. meningitidis serogroups A, C, W-135, and Y following two doses of MenACWY-CRM vaccine (at 7-9 and 12 months of age) when given concomitantly with MMRV vaccine (at 12 months) compared to when MenACWY-CRM vaccine was given alone, are reported. | 6 weeks post vaccine dose 2 | 
| Geometric Mean Titers Against Serogroups A, C, W-135 and Y, Following Two Doses of MenACWY-CRM Vaccine | The geometric mean titers (GMTs) directed against N.meningitidis serogroups A, C, W-135 and Y, following two doses of MenACWY-CRM vaccine (at 7-9 months and 12 months of age), when given concomitantly with MMRV vaccine (at 12 months) compared to when MenACWY-CRM vaccine was given alone, are reported. | 6 weeks post vaccine dose 2 | 
| Geometric Mean Titers Against Measles, Mumps, Rubella and Varicella Following One Dose of MMRV Vaccine. | The GMTs directed against measles, mumps, rubella and varicella, following one dose of MMRV vaccine (at 12 months) when given concomitantly with MenACWY-CRM vaccine compared to when MMRV vaccine was given alone, are reported. | 6 weeks post vaccination | 
| Percentages of Subjects Showing Seroconversion Response to Varicella Following Concomitant Administration of MMRV With MenACWY-CRM Vaccine. | The percentages of subjects showing seroconversion response to varicella after concomitant administration of MMRV vaccine (at 12 months) with MenACWY-CRM vaccine compared to when MMRV vaccine is given alone, is reported . Seroconversion for varicella is defined as percentage of subjects who show pre-vaccination antibody titer <1.25 gp ELISA units/mL to a post-vaccination antibody titer ≥1.25 gp ELISA units/mL. | 6 weeks post vaccination | 
| Percentages of Subjects With hSBA ≥1:4 and hSBA ≥1:8 Following One Dose of MenACWY-CRM Vaccine | The percentages of subjects with hSBA ≥1:4 and hSBA ≥1:8 after one dose of MenACWY-CRM vaccine (at 7-9 months), are reported | 1 month post vaccine dose 1 | 
| Geometric Mean Titers After One Dose of MenACWY-CRM Vaccine | The immunogenicity of one dose of MenACWY-CRM vaccine given at 7 to 9 months of age was assessed in terms of GMTs directed against N.meningitidis serogroups A, C, W-135, and Y. | 1 month post vaccine dose 1 | 
| Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination | Safety and tolerability of MenACWY-CRM and MMRV vaccines when given concomitantly compared to when either MenACWY-CRM or MMRV vaccine was administered alone is reported in terms of the number of subjects with local and systemic adverse events after vaccination. Systemic reactions including axillary temperature reported during 28 days after vaccination at 12 months of age. These included the following systemic reactions: Measles-like rash, Rubella-like rash, Varicellalike rash, injection site rash, Mumps-like symptoms and axillary temperature. | upto 7 days after any vaccination | 
| Number of Subjects Reporting Unsolicited Adverse Events After Vaccination | The safety profile of MenACWY-CRM and MMRV vaccines when given concomitantly as compared to when MenACWY-CRM or MMRV was given alone is reported in terms of number of subjects reporting unsolicited adverse events (AEs), medically significant adverse events and serious adverse events (SAEs) after vaccination. | Day 1- Day 180 (Through out the study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, toddlers, healthy, meningitis, meningococcal, measles, mumps, rubella, varicella, Prevention of Meningococcal disease types ACWY