Back to resultsSafety and Immunogenicity of Different Meningitis Vaccine Formulations in Adolescents and Young Adults
Primary Purpose
Invasive Meningococcal Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Meningococcal (groups A, C, W, Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine + OMV.
Meningococcal (group B) multicomponent recombinant adsorbed vaccine plus OMV.
Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine.
Meningococcal (groups A, C, W, Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine + qOMV.
Sponsored by
About this trial
This is an interventional prevention trial for Invasive Meningococcal Disease focused on measuring Safety, Immunogenicity, Vaccine, Meningococcal, Seroresponse
Eligibility Criteria
Inclusion Criteria:
- Healthy adolescents aged 10 through 25 years of age inclusive at the time of enrollment.
Exclusion Criteria:
- History of any meningococcal vaccine administration;
- Current or previous, confirmed or suspected disease caused by N. meningitidis;
- Pregnant or nursing (breastfeeding) mothers;
- Females of childbearing age who have not used or do not plan to use acceptable birth control measures, for the duration of the study;
- Any serious, chronic, or progressive disease;
- Known or suspected impairment/alteration of the immune system;
- 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.
Sites / Locations
- Alabama Clinical Therapeutics, 806 St. Vincent's Drive, Suite 615
- Madera Family Medical Group,1111 West 4th Street
- Center for Clinical Trials LLC, 16660 Paramount Blvd, Suite 301
- Kentucky Pediatric/Adult Research, 201 south 5th street
- Bluegrass Clinical Research Inc.5512 Bardstown Road, Suite 2
- Ohio Pediatric Research Association, 7371 Brandt Pike, Suite C
- Ohio Pediatric Research Association, 1775 Delco Park Drive
- Focus Research Group,201 Signature Place
- Specjalistyczna Przychodnia Lekarska Internistyczno-Pediatryczna,,Juniperus"s.c, ul.Kościuszki 41
- NZOZ HIPOKRATES II.sp.zo.o, ul.Pachonskiego 12
- NZOZ PRAKTIMED Sp.zo.o, ul.Strzelców 15
- Klinika Pediatrii Centrum Medycznego Kształcenia PodyplomowegoSzpital Bielański, ul. Cegłowska 80
- Katedra i Klinika Pediatrii i Chorób Infekcyjnych, ul.O.Bujwida 44
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Active Comparator
Active Comparator
Arm Label
ABCWY+OMV
ABCWY+qOMV
rMenB+OMV
MenACWY
Arm Description
Subjects in this group received two doses of "Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine" plus Outer Membrane Vesicles (OMV) administered two months apart.
Subjects in this group received two doses of "Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine" plus one quarter dose of Outer Membrane Vesicles (qOMV) administered two months apart.
Subjects in this group received two doses of "Meningococcal (group B) multicomponent recombinant adsorbed vaccine",administered two months apart.
Subjects in this group received a dose of placebo followed by one dose of "Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine" administered two months later.
Outcomes
Primary Outcome Measures
Percentages of Subjects With a Seroresponse Against N.Meningitidis Serogroups A,C,W-135,Y, After Receiving Different Formulations of MenABCWY Combination Vaccine.
Non-inferiority of immune response of two doses of two different formulations of MenABCWY vaccine to a single dose of MenACWY vaccine as measured by the percentage of subjects with hSBA seroresponse against N.meningitidis serogroups A,C,W and Y.
Seroresponse is defined as:
For subjects with a pre-vaccination hSBA titer < 1:4, a post-vaccination hSBA titer ≥ 1:8;
For subjects with a pre-vaccination hSBA titer ≥ 1:4, an increase in hSBA titer of at least four times the prevaccination titer.
Functional bactericidal antibodies directed against serogroups A,C,W,Y meningococci were measured with a serum bactericidal activity assay using human serum as the source of exogenous complement (hSBA).
Desirability Index for Each Vaccine Group, Based on Immunogenicity and Reactogenicity Parameters.
The overall desirability index (DI) used to identify the optimal formulation of the combination vaccine was based on immunogenicity and reactogenicity parameters (on a scale of 0 to 1, with 0 for an undesirable response and 1 for a highly desirable response) as follows: Between-group ratios of hSBA GMTs were calculated, adjusted for prevaccination titer and center, against serogroups A, C, W, and Y (ABCWY+OMV group or ABCWY+qOMV group vs. Placebo/ACWY group) and against the 4 serogroup B test strains (ABCWY+OMV group or ABCWY+qOMV group vs. rMenB+OMV group). Reactogenicity was measured by the percentage of doses associated with severe local and systemic solicited AEs within 3 days following vaccination. Each immunogenicity and reactogenicity endpoint was assigned its own DI based on predefined desirability functions. The overall DI was calculated using the weighted geometric mean of the DI values of each of the ten parameters to derive an overall DI for each formulation.
Secondary Outcome Measures
Percentages of Subjects With hSBA Titers ≥ 1:8 Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.
Percentages of subjects with hSBA titers ≥ 1:8 against N.meningitidis serogroups A,C,W-135 and Y, after two doses of either ABCWY+OMV or ABCWY+qOMV combination vaccine or one dose of MenACWY vaccine.
The hSBA GMTs Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.
The hSBA GMTs against N.meningitidis serogroups A,C,W-135 and Y, after two doses of either ABCWY+OMV or ABCWY+qOMV combination vaccine, or one dose of MenACWY vaccine.
Percentages of Subjects With hSBA Titers ≥ 1:5 and ≥ 1:8 Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.
The percentages of subjects with hSBA titers ≥ 1:5 and ≥ 1:8 against four different strains of N.meningitidis serogroup B, after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV vaccine.
Percentages of Subjects With at Least 4-fold Increase in hSBA Titers Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.
The percentages of subjects with at least 4-fold increase in hSBA titers against four different strains of N.meningitidis serogroup B, after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV vaccine.
4-fold increase is defined as follows;
for subjects with a prevaccination hSBA < 1:2, a postvaccination hSBA ≥ 1:8, for subjects with a prevaccination hSBA ≥ 1:2, at least a 4-fold increase.
The hSBA GMTs Against N.Meningitidis serogroupB, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.
The hSBA GMTs against N.meningitidis serogroup B after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV vaccine.
The Geometric Mean Ratio of Post vs Pre Vaccination GMTs Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.
The geometric mean ratio (GMR) of post vaccination versus pre vaccination GMTs against N.meningitidis serogroup B after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV vaccine.
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study.
The number of subjects reporting solicited local and systemic adverse events and other indicators of reactogenicity after vaccination with ABCWY+OMV, ABCWY+qOMV or rMenB+OMV or MenACWY.
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study.
The number of subjects reporting unsolicited AEs after vaccination with ABCWY+OMV, ABCWY+qOMV, rMenB+OMV or MenACWY.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01272180
Brief Title
Safety and Immunogenicity of Different Meningitis Vaccine Formulations in Adolescents and Young Adults
Official Title
Phase 2, Observer Blinded, Controlled, Randomized Multi-Center Study in Adolescents and Young Adults to Evaluate Safety and Immunogenicity of Two Different rMenB With OMV + MenACWY Combination Vaccination Formulations
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
October 2011 (Actual)
Study Completion Date
September 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Vaccines
4. Oversight
5. Study Description
Brief Summary
This study will evaluate the safety and immunogenicity of combination vaccines as compared to the reference vaccines
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Invasive Meningococcal Disease
Keywords
Safety, Immunogenicity, Vaccine, Meningococcal, Seroresponse
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
484 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ABCWY+OMV
Arm Type
Experimental
Arm Description
Subjects in this group received two doses of "Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine" plus Outer Membrane Vesicles (OMV) administered two months apart.
Arm Title
ABCWY+qOMV
Arm Type
Experimental
Arm Description
Subjects in this group received two doses of "Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine" plus one quarter dose of Outer Membrane Vesicles (qOMV) administered two months apart.
Arm Title
rMenB+OMV
Arm Type
Active Comparator
Arm Description
Subjects in this group received two doses of "Meningococcal (group B) multicomponent recombinant adsorbed vaccine",administered two months apart.
Arm Title
MenACWY
Arm Type
Active Comparator
Arm Description
Subjects in this group received a dose of placebo followed by one dose of "Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine" administered two months later.
Intervention Type
Biological
Intervention Name(s)
Meningococcal (groups A, C, W, Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine + OMV.
Intervention Description
Two injections of a combined vaccine formulation, Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine plus OMV.
Intervention Type
Biological
Intervention Name(s)
Meningococcal (group B) multicomponent recombinant adsorbed vaccine plus OMV.
Intervention Description
Two injections of Meningococcal (group B) multicomponent recombinant adsorbed vaccine plus OMV.
Intervention Type
Biological
Intervention Name(s)
Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine.
Intervention Description
One injection of saline solution placebo and one of Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine.
Intervention Type
Biological
Intervention Name(s)
Meningococcal (groups A, C, W, Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine + qOMV.
Intervention Description
Two injections of a combined vaccine formulation, Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine plus a quarter dose of OMV.
Primary Outcome Measure Information:
Title
Percentages of Subjects With a Seroresponse Against N.Meningitidis Serogroups A,C,W-135,Y, After Receiving Different Formulations of MenABCWY Combination Vaccine.
Description
Non-inferiority of immune response of two doses of two different formulations of MenABCWY vaccine to a single dose of MenACWY vaccine as measured by the percentage of subjects with hSBA seroresponse against N.meningitidis serogroups A,C,W and Y.
Seroresponse is defined as:
For subjects with a pre-vaccination hSBA titer < 1:4, a post-vaccination hSBA titer ≥ 1:8;
For subjects with a pre-vaccination hSBA titer ≥ 1:4, an increase in hSBA titer of at least four times the prevaccination titer.
Functional bactericidal antibodies directed against serogroups A,C,W,Y meningococci were measured with a serum bactericidal activity assay using human serum as the source of exogenous complement (hSBA).
Time Frame
One month after the second vaccination (Day 91)
Title
Desirability Index for Each Vaccine Group, Based on Immunogenicity and Reactogenicity Parameters.
Description
The overall desirability index (DI) used to identify the optimal formulation of the combination vaccine was based on immunogenicity and reactogenicity parameters (on a scale of 0 to 1, with 0 for an undesirable response and 1 for a highly desirable response) as follows: Between-group ratios of hSBA GMTs were calculated, adjusted for prevaccination titer and center, against serogroups A, C, W, and Y (ABCWY+OMV group or ABCWY+qOMV group vs. Placebo/ACWY group) and against the 4 serogroup B test strains (ABCWY+OMV group or ABCWY+qOMV group vs. rMenB+OMV group). Reactogenicity was measured by the percentage of doses associated with severe local and systemic solicited AEs within 3 days following vaccination. Each immunogenicity and reactogenicity endpoint was assigned its own DI based on predefined desirability functions. The overall DI was calculated using the weighted geometric mean of the DI values of each of the ten parameters to derive an overall DI for each formulation.
Time Frame
One month after the second vaccination (Day 91)
Secondary Outcome Measure Information:
Title
Percentages of Subjects With hSBA Titers ≥ 1:8 Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.
Description
Percentages of subjects with hSBA titers ≥ 1:8 against N.meningitidis serogroups A,C,W-135 and Y, after two doses of either ABCWY+OMV or ABCWY+qOMV combination vaccine or one dose of MenACWY vaccine.
Time Frame
Day 1 and one month after second vaccination (Day 91)
Title
The hSBA GMTs Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.
Description
The hSBA GMTs against N.meningitidis serogroups A,C,W-135 and Y, after two doses of either ABCWY+OMV or ABCWY+qOMV combination vaccine, or one dose of MenACWY vaccine.
Time Frame
Day 1 and one month after the second vaccination (Day 91)
Title
Percentages of Subjects With hSBA Titers ≥ 1:5 and ≥ 1:8 Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.
Description
The percentages of subjects with hSBA titers ≥ 1:5 and ≥ 1:8 against four different strains of N.meningitidis serogroup B, after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV vaccine.
Time Frame
Day 1 and one month after the second vaccination (Day 91)
Title
Percentages of Subjects With at Least 4-fold Increase in hSBA Titers Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.
Description
The percentages of subjects with at least 4-fold increase in hSBA titers against four different strains of N.meningitidis serogroup B, after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV vaccine.
4-fold increase is defined as follows;
for subjects with a prevaccination hSBA < 1:2, a postvaccination hSBA ≥ 1:8, for subjects with a prevaccination hSBA ≥ 1:2, at least a 4-fold increase.
Time Frame
One month after the second vaccination (Day 91)
Title
The hSBA GMTs Against N.Meningitidis serogroupB, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.
Description
The hSBA GMTs against N.meningitidis serogroup B after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV vaccine.
Time Frame
Day 1 and one month after the second vaccination (Day 91)
Title
The Geometric Mean Ratio of Post vs Pre Vaccination GMTs Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.
Description
The geometric mean ratio (GMR) of post vaccination versus pre vaccination GMTs against N.meningitidis serogroup B after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV vaccine.
Time Frame
One month after the second vaccination/prevaccination (Day 91/day 1)
Title
The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study.
Description
The number of subjects reporting solicited local and systemic adverse events and other indicators of reactogenicity after vaccination with ABCWY+OMV, ABCWY+qOMV or rMenB+OMV or MenACWY.
Time Frame
Day 1 through day 7 after any vaccination
Title
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study.
Description
The number of subjects reporting unsolicited AEs after vaccination with ABCWY+OMV, ABCWY+qOMV, rMenB+OMV or MenACWY.
Time Frame
Throughout the study ( Day 1 to Day 241)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy adolescents aged 10 through 25 years of age inclusive at the time of enrollment.
Exclusion Criteria:
History of any meningococcal vaccine administration;
Current or previous, confirmed or suspected disease caused by N. meningitidis;
Pregnant or nursing (breastfeeding) mothers;
Females of childbearing age who have not used or do not plan to use acceptable birth control measures, for the duration of the study;
Any serious, chronic, or progressive disease;
Known or suspected impairment/alteration of the immune system;
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Vaccines
Organizational Affiliation
Novartis Vaccines
Official's Role
Study Chair
Facility Information:
Facility Name
Alabama Clinical Therapeutics, 806 St. Vincent's Drive, Suite 615
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35205
Country
United States
Facility Name
Madera Family Medical Group,1111 West 4th Street
City
Madera
State/Province
California
ZIP/Postal Code
93637
Country
United States
Facility Name
Center for Clinical Trials LLC, 16660 Paramount Blvd, Suite 301
City
Paramount
State/Province
California
ZIP/Postal Code
90723
Country
United States
Facility Name
Kentucky Pediatric/Adult Research, 201 south 5th street
City
Bardstown
State/Province
Kentucky
ZIP/Postal Code
40004
Country
United States
Facility Name
Bluegrass Clinical Research Inc.5512 Bardstown Road, Suite 2
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40291
Country
United States
Facility Name
Ohio Pediatric Research Association, 7371 Brandt Pike, Suite C
City
Huber Heights
State/Province
Ohio
ZIP/Postal Code
45424
Country
United States
Facility Name
Ohio Pediatric Research Association, 1775 Delco Park Drive
City
Kettering
State/Province
Ohio
ZIP/Postal Code
45420
Country
United States
Facility Name
Focus Research Group,201 Signature Place
City
Lebanon
State/Province
Tennessee
ZIP/Postal Code
37087
Country
United States
Facility Name
Specjalistyczna Przychodnia Lekarska Internistyczno-Pediatryczna,,Juniperus"s.c, ul.Kościuszki 41
City
Izabelin (Warszawa)
ZIP/Postal Code
05-080
Country
Poland
Facility Name
NZOZ HIPOKRATES II.sp.zo.o, ul.Pachonskiego 12
City
Kraków
ZIP/Postal Code
31-223
Country
Poland
Facility Name
NZOZ PRAKTIMED Sp.zo.o, ul.Strzelców 15
City
Kraków
ZIP/Postal Code
31-422
Country
Poland
Facility Name
Klinika Pediatrii Centrum Medycznego Kształcenia PodyplomowegoSzpital Bielański, ul. Cegłowska 80
City
Warszawa
ZIP/Postal Code
01-809
Country
Poland
Facility Name
Katedra i Klinika Pediatrii i Chorób Infekcyjnych, ul.O.Bujwida 44
City
Wrocław
ZIP/Postal Code
50-354
Country
Poland
12. IPD Sharing Statement
Citations:
PubMed Identifier
29329168
Citation
Szenborn L, Block SL, Jackowska T, Konior R, D'Agostino D, Smolenov I, Toneatto D, Welsch JA. Immune Responses to Booster Vaccination With Meningococcal ABCWY Vaccine After Primary Vaccination With Either Investigational or Licensed Vaccines: A Phase 2 Randomized Study. Pediatr Infect Dis J. 2018 May;37(5):475-482. doi: 10.1097/INF.0000000000001896.
Results Reference
derived
Learn more about this trial
Safety and Immunogenicity of Different Meningitis Vaccine Formulations in Adolescents and Young Adults
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