Immunogenicity and Safety of the Concomitant Administration of a Tdap Vaccine and Meningococcal ACWY Conjugate Vaccine in Healthy Subjects Aged 11-25 Years

Study Overview
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Brief Summary
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Immunogenicity and Safety of the Concomitant Administration of a Tdap Vaccine and Meningococcal ACWY Conjugate Vaccine in Healthy Subjects Aged 11-25 Years

Official Title
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A Phase 3, Multi-Center, Observer Blind, Controlled, Randomized Study to Compare the Immunogenicity and Safety of the Concomitant Administration of a Combined Tetanus, Reduced Diphtheria, and Acellular Pertussis (Tdap) Vaccine and Chiron (Now Novartis) Meningococcal ACWY Conjugate Vaccine, With Either One Dose of Acellular Pertussis (Tdap) Vaccine, or One Dose of Chiron (Now Novartis) Meningococcal ACWY Conjugate Vaccine, in Healthy Subjects Aged 11-25 Years

Conditions
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Meningococcal Disease, Meningococcal Meningitis

Intervention / Treatment
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* Biological: Meningococcal ACWY conjugate vaccine (MenACWY-CRM)
* Biological: Combined tetanus, reduced diphtheria and acellular pertussis vaccine (Tdap)
* Biological: saline placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female 11-25 years old healthy subjects; who had received the primary immunization with a vaccine containing DT or Tdap antigens and a T, Td, or Tdap booster injection at least 5 years prior to study entry Exclusion Criteria: previous ascertained or suspected disease caused by N. meningitidis previously been immunized with a meningococcal vaccine or vaccine containing meningococcal antigen(s) serious acute, chronic or progressive disease history of any anaphylaxis, serious vaccine reactions, or allergy to any vaccine component known or suspected impairment/alteration of immune function, either congenital or acquired

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 25 Years

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tdap + MenACWY-CRM<br>Subjects received Tdap and MenACWY-CRM vaccines concomitantly, in separate arms | Biological: Meningococcal ACWY conjugate vaccine (MenACWY-CRM)<br> <br> Biological: Combined tetanus, reduced diphtheria and acellular pertussis vaccine (Tdap)<br> <br> |
| Experimental: Tdap + saline<br>Subjects received Tdap vaccine and saline (placebo) concomitantly, in separate arms | Biological: Combined tetanus, reduced diphtheria and acellular pertussis vaccine (Tdap)<br> <br> Biological: saline placebo<br>* 4.5 mg sodium chloride per 0.5 ml dose<br>|
| Experimental: MenACWY-CRM + saline<br>Subjects received MenACWY-CRM vaccine and saline (placebo) concomitantly, in separate arms | Biological: Meningococcal ACWY conjugate vaccine (MenACWY-CRM)<br> <br> Biological: saline placebo<br>* 4.5 mg sodium chloride per 0.5 ml dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With an Immune Response Against Diphtheria, Tetanus and Pertussis, When Tdap is Concomitantly Administered With MenACWY-CRM Compared to Tdap Given Concomitantly With Saline Placebo | To demonstrate that the immunogenicity of one injection of Tdap vaccine, concomitantly administered with MenACWY-CRM vaccine, is not inferior to that of one injection of Tdap vaccine, concomitantly administered with saline placebo, in terms of the percentage of subjects with antibody levels against diphtheria toxin ≥ 1.0 IU/mL and against tetanus toxin ≥ 1.0 IU/mL and the percentage of subjects with at least 4 fold increase in antibody levels against pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) at 1 month after immunization, as measured by enzyme linked immunosorbent assay (ELISA). | 1 month after vaccination (Day 29) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Anti-diphtheria and Anti-tetanus Concentrations ≥ 0.1 IU/mL When Tdap is Administered Concomitantly With MenACWY-CRM Vaccine Compared to Tdap Given Concomitantly With Saline Placebo | The percentage of subjects with anti-diphtheria and anti-tetanus concentrations ≥ 0.1 IU/mL (as measured by ELISA) following concomitant administration of Tdap vaccine with MenACWY-CRM vaccine as compared to when Tdap was given concomitantly with saline placebo. | 1 month after vaccination (Day 29) | 
| Geometric Mean Concentrations (GMCs) of Antibodies Against Diphtheria,Tetanus and Pertussis Antigens After Concomitant Administration of Tdap With MenACWY-CRM Compared to Tdap Given Concomitantly With Saline Placebo | The geometric mean concentrations of antibodies ≥ 0.1 IU/mL against diphtheria, tetanus and pertussis (PT, FHA and PRN) antigens in subjects, as measured by ELISA, following concomitant administration of Tdap with MenACWY-CRM as compared to when Tdap given concomitantly with saline placebo. | 1 month after vaccination (Day 29) | 
| Geometric Mean Ratios of Antibody Concentrations Against Diphtheria,Tetanus and Pertussis Antigens When Tdap is Administered Concomitantly With MenACWY-CRM Vaccine Compared to Tdap Given Concomitantly With Saline Placebo | The geometric mean ratios (GMRs- day 29/day 1) of post-vaccination versus pre- vaccination antibody concentrations against diptheria, tetanus and pertussis (PT, FHA and PRN) antigens following concomitant administration of Tdap vaccine with MenACWY-CRM vaccine as compared to when Tdap was given concomitantly with saline placebo. | 1 month after vaccination (Day 29) | 
| Percentage of Subjects With Serum Bactericidal Antibody Titers ≥1:4 and ≥1:8, When MenACWY-CRM is Concomitantly Administered With Tdap Vaccine Compared to MenACWY-CRM Given Concomitantly With Saline Placebo | The percentage of subjects with serum bactericidal antibody titers(hSBA) ≥ 1:4 and ≥ 1:8 against Neisseria meningitidis serogroups A,C,W and Y,following concomitant administration of MenACWY-CRM vaccine with Tdap vaccine as compared to when MenACWY-CRM was given concomitantly with saline placebo. The serum bactericidal antibodies directed against N.meningitidis serogroup A, C, W and Y, are measured by human complement Serum Bactericidal Assay (hSBA). | 1 month after vaccination (Day 29) | 
| The hSBA Geometric Mean Titers Against N.Meningitidis Serogroups A,C,W and Y, When MenACWY-CRM is Concomitantly Administered With Tdap Vaccine Compared to MenACWY-CRM Given Concomitantly With Saline Placebo | The hSBA geometric mean titers (GMTs) against N.meningitidis serogroups A,C,W and Y, at baseline and at one month, following concomitant administration of MenACWY-CRM vaccine with Tdap vaccine, as compared to when MenACWY-CRM was given concomitantly with saline placebo. | 1 month after vaccination (Day 29) | 
| Geometric Mean Ratios of hSBA Titers Against N.Meningitidis Serogroups A,C,W and Y, When MenACWY-CRM is Concomitantly Administered With Tdap Compared to MenACWY-CRM Given Concomitantly With Saline Placebo | The geometric mean ratios (GMRs-day 29/day1)of post-vaccination versus pre- vaccination hSBA titers against N.meningitidis serogroups A,C,W and Y, when MenACWY-CRM vaccine is concomitantly administered with Tdap vaccine as compared to when MenACWY-CRM was given concomitantly with saline placebo. | 1 month after vaccination (Day 29) | 
| Percentage of Subjects With hSBA Seroresponse, When MenACWY-CRM is Concomitantly Administered With Tdap Compared to MenACWY-CRM Given Concomitantly With Saline Placebo | The percentage of subjects showing an hSBA seroresponse against N.meningitidis serogroups A,C,W and Y, following concomitant administration of MenACWY-CRM vaccine with Tdap vaccine as compared to when MenACWY-CRM was given concomitantly with saline placebo. Seroresponse to MenACWY-CRM is defined as a pre-vaccination hSBA titer < 1:4 to a post-vaccination hSBA titer of ≥ 1:8 or a pre-vaccination hSBA titer ≥ 1:4 to a post-vaccination titer of at least four times the baseline hSBA titer. | 1 month after vaccination (Day 29) | 
| Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap is Concomitantly Administered With MenACWY-CRM Compared to When MenACWY-CRM is Concomitantly Administered With Saline Placebo | The number of subjects reporting solicited local and systemic reactions following concomitant administration of MenACWY-CRM vaccine and Tdap vaccine as compared to when MenACWY-CRM vaccine was concomitantly administered with saline placebo. | Day 1-7 after any vaccination | 
| Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap is Concomitantly Administered With MenACWY-CRM Compared to When Tdap is Concomitantly Administered With Saline Placebo | The number of subjects reporting solicited local and systemic reactions following concomitant administration of MenACWY-CRM vaccine and Tdap vaccine as compared to when Tdap was concomitantly administered with saline placebo | Day 1-7 after any vaccination | 
| Number of Subjects With Unsolicited Adverse Events When Tdap is Concomitantly Administered With MenACWY-CRM Compared to MenACWY-CRM or Tdap Concomitantly Administered With Saline Placebo | The number of subjects reporting any unsolicited adverse events (AEs) when Tdap is concomitantly administered with MenACWY-CRM as compared to when MenACWY-CRM vaccine or Tdap vaccine was concomitantly administered with saline placebo. | Throughout the study (Day 1 to Day 181) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningitis, healthy subject, vaccine