Novartis Vaccine and Diagnostics Carriage Trial

Study Overview
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Brief Summary
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The purpose of this trial was to evaluate the effect of Novartis Vaccine's Meningococcal vaccines on carriage of Neisseria meningitidis in a young adult population.

Official Title
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A Phase 3 Observer Blind Randomized, Multi-center, Controlled Study to Evaluate the Effect of Novartis Vaccine's Meningococcal B Recombinant and MenACWY Conjugate Vaccines on Pharyngeal Carriage of N. Meningitidis in Young Adults

Conditions
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N. Meningitidis Carriage

Intervention / Treatment
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* Biological: Meningococcal B Recombinant + Outer Membrane Vesicle vaccine (rMenB+OMV NZ)
* Biological: MenACWY-CRM conjugate vaccine
* Biological: Japanese Encephalitis vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects, 18-24 years of age who provided written informed consent at the time of enrollment; Subjects who were available for all the visits scheduled in the study; Subjects who were in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator. Exclusion Criteria: History of any serogroup B meningococcal vaccine administration; Current or previous, confirmed or suspected disease caused by N. meningitidis; Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days of enrollment; Significant acute or chronic infection within the previous 7 days or fever (defined as oral temperature ≥38ºC) within the previous day; Antibiotics within 3 days (72 hours) prior to enrollment; Pregnancy or nursing (breastfeeding) mothers; Females of childbearing age who had not used or did not plan to use acceptable birth control measures, for the 12 months duration of the study. Oral, injected or implanted hormonal contraceptive, diaphragm, condom, intrauterine device or sexual abstinence were considered acceptable forms of birth control. If sexually active the subject must have been using one of the accepted birth control methods for at least 30 days prior to study entry; Any serious chronic or progressive disease (e.g., neoplasm, diabetes, cardiac disease, hepatic disease, progressive neurological disease or seizure disorder; autoimmune disease, human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), or blood dyscrasias or diathesis, signs of cardiac or renal failure or severe malnutrition); Known or suspected impairment/alteration of the immune system, immunosuppressive therapy, including use of corticosteroids in immunosuppressive doses or chronic use of inhaled high-potency corticosteroids within the previous 60 days. [Use of topical corticosteroids administered during the study in limited areas (i.e., eczema on knees or face or elbows) of the body were allowed]; use of immunostimulants; Receipt of blood, blood products and/or plasma derivatives, or a parenteral immunoglobulin preparation within the previous 90 days; History of severe allergic reactions after previous vaccinations or hypersensitivity to any vaccine component; Participation in another clinical trial within the last 90 days or planned for during study; Family members and household members of research staff; Any condition which in the opinion of the investigator and/or the Regional MD may interfere with the evaluation of the study objectives.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 24 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rMenB+OMV<br>Subjects (18-24 years) received two injections of rMenB+OMV NZ vaccine, one month apart | Biological: Meningococcal B Recombinant + Outer Membrane Vesicle vaccine (rMenB+OMV NZ)<br> <br> |
| Experimental: MenACWY<br>Subjects (18-24 years) received one injection of MenACWY-CRM vaccine followed by one injection of placebo, one month apart | Biological: MenACWY-CRM conjugate vaccine<br> <br> |
| Active Comparator: Control<br>Subjects (18-24 years) received two injections of a control vaccine (Japanese Encephalitis), one month apart | Biological: Japanese Encephalitis vaccine<br> <br> * Other names: IXIARO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With Carriage of Virulent Sequence Types (ST) of Neisseria Meningitidis Group B, One Month After Completion of rMenB+OMV NZ Vaccination | Percentages of subjects with carriage of virulent sequence types (ST) of Neisseria meningitidis group B, one month after completion of rMenB+OMV NZ vaccination. The carriage rate of virulent sequence types (ST) of N. meningitidis group B (genogroupable) in subjects, one month after receiving two doses of rMenB+OMV NZ, as compared to the control group, was reported. Virulent ST types are defined as Clonal Complex multi locus sequence typing (MLST) or ST type being the same compared to history data (Clonal Complexes MLST or ST types found to be virulent and causing diseases) from the years 2006 to 2010. | 61 days (31 days after receiving the second injection) | 
| Percentages of Subjects With Combined Carriage of N. Meningitidis Serogroups A, C, W and Y, One Month After MenACWY-CRM Vaccination | The percentage of subjects with combined carriage rate of N. meningitidis serogroups A, C, W and Y in subjects, one month after receiving a single dose of MenACWY-CRM conjugate vaccine as compared to the control group is reported. | 31 days after MenACWY-CRM injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With Carriage of All ST Types of N. Meningitidis B (Genogroupable) at Different Time Points Following rMenB+OMV NZ Vaccination | The percentage of subjects with carriage of all (virulent + non-virulent) ST types of N. meningitidis B (genogroupable) in subjects at different time points of the study after administration of two doses of rMenB+OMV NZ conjugate vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With Carriage of Virulent ST Types of N. Meningitidis Group B at Any Time Point After rMenB+OMV NZ Vaccination | Percentage of subjects with carriage of virulent ST types of N. meningitidis group B (genogroupable) in subjects at different time points of the study point after administration of two doses of rMenB+OMV NZ conjugate vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With Carriage of Nonvirulent ST Types of N. Meningitidis Group B at Any Time Point After rMenB+OMV NZ Vaccination | Percentage of subjects with carriage of nonvirulent ST types of N. meningitidis group B (genogroupable) in subjects at different time points of the study point after administration of two doses of rMenB+OMV NZ conjugate vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With Carriage of All N.Meningitidis Strain at Different Time Points After rMenB+OMV NZ Vaccination | Percentage of subjects with carriage of all N.meningitidis strains combined in subjects at different time points of the study after administration of two doses of rMenB+OMV NZ vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With Carriage of N.Meningitidis ABCWY Genogroups at Different Time Points After rMenB+OMV NZ Vaccination | Percentages of subjects with carriage of N.meningitidis ABCWY genogroups in subjects at different time points of the study after administration of two doses of rMenB+OMV NZ vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With Carriage of N.Meningitidis ACWY Genogroups at Different Time Points After rMenB+OMV NZ Vaccination | Percentages of subjects with carriage of N.meningitidis ACWY genogroups in subjects at different time points of the study after administration of two doses of rMenB+OMV NZ vaccine as compared to the control group is reported | Up to 361 days after vaccination | 
| Percentages of Subjects With Carriage of N.Meningitidis Serogroups A,C,W or Y at Different Time Points After rMenB+OMV NZ Vaccination | Percentages of subjects with carriage of N.meningitidis serogroups A,C,W or Y in subjects at different time points of the study after administration of two doses of rMenB+OMV NZ vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With Carriage of N.Meningitidis Genogroup Y at Different Time Points After rMenB+OMV NZ Vaccination | Percentages of subjects with carriage of N.meningitidis genogroup Y in subjects at different time points of the study after administration of two doses of rMenB+OMV NZ vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With Carriage of N.Meningitidis Serogroup Y at Different Time Points After rMenB+OMV NZ Vaccination | Percentages of subjects with carriage of N.meningitidis serogroup Y in subjects at different time points of the study after administration of two doses of rMenB+OMV NZ vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subject With Carriage of N. Meningitidis Genogroups ACWY at Different Time Points After MenACWY-CRM Vaccination | Percentages of subject with carriage of N. meningitidis genogroups ACWY in subjects at different time points of the study after administration of a single dose of MenACWY-CRM conjugate vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With Carriage of N. Meningitidis Serogroups ACWY at Different Time Points After MenACWY-CRM Vaccination | Percentages of subjects with carriage of N. meningitidis serogroups ACWY in subjects at different time points of the study after administration of a single dose of MenACWY-CRM conjugate vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With Carriage of N. Meningitidis Genogroup Y at Different Time Points After MenACWY-CRM Vaccination | Percentages of subjects with carriage of N. meningitidis genogroup Y in subjects at different time points of the study after administration of a single dose of MenACWY-CRM conjugate vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With Carriage of N. Meningitidis Serogroup Y at Different Time Points After MenACWY-CRM Vaccination | Percentages of subjects with carriage of N. meningitidis serogroup Y in subjects at different time points of the study after administration of a single dose of MenACWY-CRM conjugate vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With New Acquisition of Pharyngeal Carriage of All ST Types of N. Meningitidis Genogroup B at Different Time Points Following rMenB+OMV NZ Vaccination | The percentages of subjects with newly acquired pharyngeal carriage of all ST types of N. meningitidis genogroup B in subjects at different time points of the study after administration of two doses of rMenB+OMV NZ conjugate vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With New Acquisition of Pharyngeal Carriage of Virulent ST Types of N. Meningitidis Genogroup B at Different Time Points Following rMenB+OMV NZ Vaccination | The percentages of subjects with newly acquired pharyngeal carriage of virulent ST types of N. meningitidis genogroup B in subjects at different time points of the study after administration of two doses of rMenB+OMV NZ conjugate vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With New Acquisition of Pharyngeal Carriage of All N. Meningitidis at Different Time Points Following rMenB+OMV NZ Vaccination | The percentages of subjects with newly acquired pharyngeal carriage of all N. meningitidis in subjects at different time points of the study after administration of two doses of rMenB+OMV NZ conjugate vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With New Acquisition of Pharyngeal Carriage of N. Meningitidis Genogroups ABCWY at Different Time Points Following rMenB+OMV NZ Vaccination | The percentages of subjects with newly acquired pharyngeal carriage of N. meningitidis genogroups ABCWY in subjects at different time points of the study after administration of two doses of rMenB+OMV NZ conjugate vaccine as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With New Acquisition of Pharyngeal Carriage of N. Meningitidis Serogroups ACWY at Different Time-points After MenACWY-CRM Vaccination | The percentages of subjects with newly acquired pharyngeal carriage of N.meningitidis serogroups A,C, W or Y at different time-points in the study after MenACWY-CRM vaccination as compared to the control group is reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With New Acquisition of Pharyngeal Carriage of N. Meningitidis Serogroup Y at Different Time-points After MenACWY-CRM Vaccination | The percentages of subjects with newly acquired pharyngeal carriage of N.meningitidis serogroup Y at different time-points in the study after MenACWY-CRM vaccination as compared to the control group is reported. | Up to 361 days after vaccination | 
| The Duration of Any Carriage of N.Meningitidis Strains After Vaccination With rMenB+OMV | The duration of carriage of any N.meningitidis strains after receiving two doses of rMenB+OMV compared to that in the control group is reported. | Any post vaccination timepoint (the date of first observation of the carriage and the date of the last observation of the carriage) | 
| The Duration of Carriage of Any N. Meningitidis Strain After Vaccination With MenACWY-CRM | The duration of carriage of any N meningitidis strain after receiving one dose MenACWY-CRM as compared to that in control group is reported. | Any time post vaccination (the date of first observation of the carriage and the date of the last observation of the carriage) | 
| The Duration of Carriage After New Acquisition N.Meningitidis Strains Following Vaccination With rMenB+OMV Vaccine | The duration of carriage after new acquisition of N.meningitidis strains after receiving two doses of rMenB+OMV vaccine compared to that in the control group is reported. | Any post vaccination timepoint (the date of first observation of the carriage and the date of the last observation of the carriage) | 
| The Duration of Carriage After New Acquisition N.Meningitidis Strains Following Vaccination With MenACWY Vaccine | The duration of carriage after new acquisition of N.meningitidis strains after receiving one dose of MenACWY-CRM vaccine compared to that in the control group is reported. | Any post vaccination timepoint (the date of first observation of the carriage and the date of the last observation of the carriage) | 
| Percentages of Subjects With N. Meningitidis Carriage of Virulent ST of Group B, Stratified by Pre-vaccination hSBA Titer After rMenB+OMV NZ Vaccination | The percentages of subjects with N. meningitidis Virulent ST of serogroup B, at different time points of the study, in subjects stratified by pre-vaccination hSBA (<4 and ≥4) titers after administration of two doses of rMenB+OMV NZ vaccine as compared to the control group is reported. The serum bactericidal antibodies directed against N.meningitides serogroups, are measured by Serum Bactericidal Assay using human complement (hSBA). H44/76, 5/99 and NZ98/254 are strains in serogroup B. | Up to 361 days after vaccination | 
| Percentages of Subjects With N. Meningitidis Carriage of Serogroup Y After MenACWY-CRM Vaccination, Stratified by Pre-vaccination hSBA Titers | The prevalence of carriage of N. meningitidis serogroup Y, at different time points of the study, in subjects stratified by pre-vaccination hSBA (<8 and ≥8) titers, after administration of one dose of MenACWY-CRM vaccine as compared to the control group is reported. | Up to 12 months after vaccination | 
| Percentages of Subjects With hSBA Titers ≥1:4 Against N. Meningitidis Serogroup B After rMenB+OMV NZ or MenACWY-CRM Vaccination Compared to Control Group | The percentages of subjects with hSBA titers ≥1:4 against the three strains of N. meningitidis B, after rMenB+OMV NZ or MenACWY-CRM vaccination at different time points of the study as compared to the control group are reported. | Up to 361 days after vaccination | 
| The hSBA Geometric Mean Titers Against N. Meningitidis Serogroup B, After rMenB+OMV NZ or MenACWY-CRM Vaccination Compared to Control Group. | The hSBA Geometric Mean Titers (GMTs) against the three strains of N. meningitidis serogroup B, after rMenB+OMV NZ or MenACWY-CRM vaccination at different time points of the study as compared to the control group are reported. | Up to 361 days after vaccination | 
| Percentages of Subjects With hSBA Titers ≥1:8 Against N. Meningitidis Serogroup C and Y, After rMenB+OMV NZ or MenACWY-CRM Vaccination Compared to Control Group. | The percentages of subjects with hSBA titers ≥1:8 against N. meningitidis serogroups C and Y, after rMenB+OMV NZ or MenACWY-CRM vaccination at different time points of the study as compared to the control group are reported. As serogroup A and W strains were not detected in substantial proportion of subjects during pharyngeal carriage analysis, these serogroups were not tested. | Up to 361 days after vaccination | 
| The hSBA Geometric Mean Titers Against N. Meningitidis Serogroup C and Y, After rMenB+OMV NZ or MenACWY-CRM Vaccination Compared to Control Group. | The hSBA antibody titers against N. meningitidis serogroups C and Y after rMenB+OMV NZ or MenACWY-CRM vaccination at different time points of the study as compared to the control group, are reported as GMTs. Serogroups A and W were not analysed. | Up to 361 days after vaccination | 
| Percentages of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroups C and Y After Vaccination With rMenB+OMV NZ or MenACWY-CRM Compared to Control Group. | The percentages of subjects with hSBA seroresponse against N. meningitidis serogroups C and Y, after rMenB+OMV NZ or MenACWY-CRM vaccination as compared to the control group are reported. Seroresponse to N. meningitidis serogroups Cand Y is defined as :(1)for subjects with a pre-vaccination hSBA titer < 1:4 to a post-vaccination hSBA titer ≥ 1:8 or (2) for subjects with a pre-vaccination hSBA titer ≥ 1:4, an increase in hSBA titer of at least four times the pre-vaccination titer. Analysis was not done for serogroups A and W. | 61 days | 
| The hSBA Geometric Mean Titers Against N. Meningitidis Serogroups C and Y in Subjects (Who Have Received a Prior Dose of MenC Vaccine) After Vaccination With MenACWY-CRM in This Study Compared to Control Group | The hSBA geometric mean titers against the N. meningitidis serogroups C and Y in subjects (who have received a prior dose of MenC vaccine) after MenACWY-CRM vaccination at different time points of the study as compared to the control group are reported. Analysis was not done for serogroups A and W. | Up to 361 days after vaccination | 
| Percentages of Subjects (Who Have Received a Prior Dose of MenC Vaccine) With hSBA Titers ≥1:8 Against N. Meningitidis Serogroups C and Y After Vaccination With MenACWY-CRM in This Study Compared to Control Group. | The percentages of subjects (who have received a prior dose of MenC vaccine) with hSBA titers ≥1:8 against N. meningitidis serogroups C and Y after receiving MenACWY-CRM vaccination in this study as compared to the control group are reported. Analysis was not done for serogroups A and W. | Up to 361 days after vaccination | 
| Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Vaccination With rMenB+OMV NZ or MenACWY-CRM Compared to Control Group | The safety and tolerability of two doses of rMenB+OMV NZ vaccine (Group rMenB+OMV) and one dose of MenACWY-CRM vaccine (Group MenACWY) was assessed in terms of number of subjects with solicited local and systemic adverse events and other adverse events, following vaccination and compared to that of the control group. | 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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Meningococcal vaccines, Meningococcal B, Meningococcal ACWY serogroups