Immunogenicity, Safety and 1 Year Persistence of Antibodies After Either One or Two Doses of Meningococcal ACWY Conjugate Vaccine in Healthy Children 2 Through 10 Years of Age.
Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT01682876
Collaborator
(none)
715
19
4
19.7
37.6
1.9
Study Details
Study Description
Brief Summary
This study was designed to conduct a comparative trial to further evaluate the safety, immunogenicity and antibody persistence of two doses of Novartis MenACWY conjugate vaccine, given 2 months apart, versus one dose of Novartis MenACWY conjugate vaccine in children 2 through 10 years of age.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
715 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
A Phase 3b, Randomized, Observer-Blind, Placebo-Controlled Multi-Center Study Comparing Immunogenicity, Safety and 1 Year Persistence of Antibodies After Either One or Two Doses of Novartis Meningococcal ACWY Conjugate Vaccine, Administered to Healthy Children 2 to 10 Years of Age.
Actual Study Start Date
:
Oct 7, 2012
Actual Primary Completion Date
:
Jul 2, 2013
Actual Study Completion Date
:
May 30, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: 2 through 5 years (1 Vac) MenACWY-CRM 1 Subjects 2 through 5 years received one vaccination of MenACWY-CRM |
Biological: MenACWY-CRM
The investigational meningococcal (groups A, C, Y, and W-135 vaccine) oligosaccharide diphtheria CRM197 conjugate vaccine (MenACWY-CRM) was administered intramuscularly in the nondominant arm
|
| Active Comparator: 2 through 5 years (2 Vac) MenACWY-CRM 2 Subjects 2 through 5 years received two vaccinations of MenACWY-CRM |
Biological: MenACWY-CRM
The investigational meningococcal (groups A, C, Y, and W-135 vaccine) oligosaccharide diphtheria CRM197 conjugate vaccine (MenACWY-CRM) was administered intramuscularly in the nondominant arm
|
| Placebo Comparator: 6 through 10 years (1 Vac) MenACWY-CRM 3 Subjects 6 through 10 years received one vaccination of MenACWY-CRM |
Biological: MenACWY-CRM
The investigational meningococcal (groups A, C, Y, and W-135 vaccine) oligosaccharide diphtheria CRM197 conjugate vaccine (MenACWY-CRM) was administered intramuscularly in the nondominant arm
|
| Active Comparator: 6 through 10 years (2 Vac) MenACWY-CRM 4 Subjects 6 through 10 years received two vaccinations of MenACWY-CRM |
Biological: MenACWY-CRM
The investigational meningococcal (groups A, C, Y, and W-135 vaccine) oligosaccharide diphtheria CRM197 conjugate vaccine (MenACWY-CRM) was administered intramuscularly in the nondominant arm
|
Outcome Measures
Primary Outcome Measures
- Non-inferiority of Two Vaccinations Versus One Vaccination of MenACWY-CRM, by Age Cohort, as Measured by the Percentage of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroups A, C, W and Y, at 1 Month After Last Vaccination [One Month After Last Vaccination ( day 86)]
Immunogenicity was measured as the percentage of subjects with overall seroresponse and associated 2-sided 97.5% Clopper-Pearson confidence interval (CI), directed against N. meningitidis serogroups A, C, W and Y, by serum bactericidal assay using human complement (hSBA) at 1 month after one vaccination or two vaccinations of MenACWY-CRM given two months apart. Seroresponse is defined as: a. postvaccination hSBA titer ≥1:8 for subjects with a prevaccination hSBA titer <1:4; b. for subjects with a prevaccination hSBA ≥1:4, an increase of at least four times of the prevaccination hSBA titer.
- Superiority of Two Vaccinations Versus One Vaccination of MenACWY-CRM, by Age Cohort, as Measured by the Percentage of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroups A, C, W and Y, at 1 Month After Last Vaccination [One Month After Last Vaccination (day 86)]
Immunogenicity was measured as the percentage of subjects with overall seroresponse and associated 2-sided 95% CI, directed against N. meningitidis serogroups A, C, W and Y, by hSBA at 1 month after one vaccination or two vaccinations of MenACWY-CRM. Seroresponse -postvaccination hSBA titer ≥1:8 for subjects with a prevaccination hSBA titer <1:4 and for subjects with a prevaccination hSBA ≥1:4, an increase of at least four times of the prevaccination hSBA titer.
Secondary Outcome Measures
- Percentage of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Month After One or Two Vaccination(s) of MenACWY-CRM [One Month After Last Vaccination (day 86)]
Immunogenicity was measured as the percentage of subjects who achieved hSBA titer ≥1:8 and associated 95% CI, at one month after one vaccination or two vaccinations of MenACWY-CRM.
- Geometric Mean Titers of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Month After One or Two Vaccination(s) of MenACWY-CRM [One Month After Last Vaccination (day 86)]
Immunogenicity was measured as hSBA geometric mean titers (GMTs) and 95% CI against N. meningitidis serogroups A, C, W and Y, one month after one vaccination or two vaccinations of MenACWY-CRM.
- Percentage of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Year After One or Two Vaccination(s) of MenACWY-CRM [One year after one vaccination or two vaccinations (day 422).]
Immunogenicity was measured as the percentage of subjects with hSBA titer ≥1:8 and associated 95% CI at one year after one vaccination or two vaccinations of MenACWY-CRM.
- Geometric Mean Titers of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Year After One or Two Vaccination(s) of MenACWY-CRM [One year after one vaccination or two vaccinations (day 422).]
Immunogenicity was measured as hSBA GMTs and 95% CI against N. meningitidis serogroups A, C, W and Y at one year after one vaccination or two vaccinations of MenACWY-CRM.
- Number of 2 to 5 Years-Old Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination [From Days 1-7 after each vaccination]
Safety was assessed as the number of 2 to 5 years-old subjects who reported solicited local and systemic adverse events from day 1 up to and including day 7 after one or two vaccination(s) of MenACWY-CRM
- Numbers of 6 to 10 Years-Old Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination [From Days 1-7 after each vaccination]
Safety was assessed as the number of 6 to 10 years-old subjects who reported solicited local and systemic adverse events from day 1 up to and including day 7 after one or two vaccination(s) of MenACWY-CRM
- Number of Subjects Who Reported Selected AEs After Any Vaccination [Day 1 to Day 86]
Safety was assessed as the number subjects who reported Selected AEs from day 1 up to day 86 after one or two vaccination(s) of MenACWY-CRM
- Number of Subjects Who Reported Selected AEs After Any Vaccination [Day 1 to Day 422]
Safety was assessed as the number subjects who reported Selected AEs from day 1 up to day 422 after one or two vaccination(s) of MenACWY-CRM
Eligibility Criteria
Criteria
Ages Eligible for Study:
2 Years
to 10 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
- Healthy children, 2 to 10 years of age who have up to date routine childhood vaccination, according to U.S. ACIP recommendations
Exclusion Criteria:
-
Unwilling or unable to give written informed assent or consent to participate in the study.
-
Perceived to be unreliable or unavailable for the duration of the study period.
-
Previous confirmed or suspected disease caused by N. meningitidis.
-
Previously immunized with a meningococcal vaccine (licensed or investigational).
-
Receipt of any investigational or non-registered product within 30 days prior to enrolment or who expect to receive an investigational drug or vaccine prior to the completion of the study.
-
Receipt or plan to receive any vaccines within 30 days before and after administration of each dose of the study vaccine.
(certain exceptions influenza vaccines apply)
-
Significant acute infection within the 7 days prior to enrolment or body temperature of 38°C or greater within 3 days prior to enrolment.
-
Previous serious acute, chronic or progressive disease, epilepsy or any progressive neurological disease or history of Guillain-Barre syndrome.
-
History of any anaphylaxis, serious vaccine reactions, or allergy to any vaccine components
-
Impairment/alteration of immune function, either congenital or acquired or resulting from (for example):
-
receipt of immunosuppressive therapy,
-
receipt of immunostimulants,
-
receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives.
- Known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Birmingham | Alabama | United States | 35205 |
| 2 | GSK Investigational Site | Sacramento | California | United States | 95822 |
| 3 | GSK Investigational Site | Lake Mary | Florida | United States | 32746 |
| 4 | GSK Investigational Site | Marietta | Georgia | United States | 30062 |
| 5 | GSK Investigational Site | Woodstock | Georgia | United States | 30189 |
| 6 | GSK Investigational Site | Council Bluffs | Iowa | United States | 51503 |
| 7 | GSK Investigational Site | Louisville | Kentucky | United States | 40291 |
| 8 | GSK Investigational Site | Metairie | Louisiana | United States | 70006 |
| 9 | GSK Investigational Site | Niles | Michigan | United States | 49120 |
| 10 | GSK Investigational Site | Stevensville | Michigan | United States | 49127 |
| 11 | GSK Investigational Site | Bellevue | Nebraska | United States | 68005 |
| 12 | GSK Investigational Site | Fremont | Nebraska | United States | 68025 |
| 13 | GSK Investigational Site | Omaha | Nebraska | United States | 68134 |
| 14 | GSK Investigational Site | Johnson City | New York | United States | 13790 |
| 15 | GSK Investigational Site | Cleveland | Ohio | United States | 44121 |
| 16 | GSK Investigational Site | Cleveland | Ohio | United States | 44122 |
| 17 | GSK Investigational Site | Austin | Texas | United States | 78705 |
| 18 | GSK Investigational Site | Fort Worth | Texas | United States | 76135 |
| 19 | GSK Investigational Site | West Jordan | Utah | United States | 84088 |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01682876
Other Study ID Numbers:
- 205238
- V59_57
- 2011-004421-27
First Posted:
Sep 11, 2012
Last Update Posted:
Jun 14, 2019
Last Verified:
Jun 1, 2019
Keywords provided by GlaxoSmithKline
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Subjects were enrolled at 22 locations |
|---|---|
| Pre-assignment Detail | All enrolled subjects were included in the trial. |
| Arm/Group Title | 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) |
|---|---|---|---|---|
| Arm/Group Description | Subjects 2-5 years of age received two MenACWY-CRM vaccinations | Subjects 2-5 years of age received one MenACWY-CRM vaccination | Subjects 6-10 years of age received two MenACWY-CRM vaccinations | Subjects 6-10 years of age received one MenACWY-CRM vaccination |
| Period Title: Overall Study | ||||
| STARTED | 176 | 183 | 180 | 176 |
| COMPLETED | 155 | 163 | 169 | 157 |
| NOT COMPLETED | 21 | 20 | 11 | 19 |
Baseline Characteristics
| Arm/Group Title | 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Subjects 2-5 years of age received two MenACWY-CRM vaccinations | Subjects 2-5 years of age received one MenACWY-CRM vaccination | Subjects 6-10 years of age received two MenACWY-CRM vaccinations | Subjects 6-10 years of age received one MenACWY-CRM vaccination | Total of all reporting groups |
| Overall Participants | 176 | 183 | 180 | 176 | 715 |
| Age (year) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [year] |
3.5
(1.1)
|
3.6
(1.2)
|
7.8
(1.4)
|
7.8
(1.4)
|
5.7
(2.5)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
84
47.7%
|
88
48.1%
|
97
53.9%
|
87
49.4%
|
356
49.8%
|
| Male |
92
52.3%
|
95
51.9%
|
83
46.1%
|
89
50.6%
|
359
50.2%
|
Outcome Measures
| Title | Non-inferiority of Two Vaccinations Versus One Vaccination of MenACWY-CRM, by Age Cohort, as Measured by the Percentage of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroups A, C, W and Y, at 1 Month After Last Vaccination |
|---|---|
| Description | Immunogenicity was measured as the percentage of subjects with overall seroresponse and associated 2-sided 97.5% Clopper-Pearson confidence interval (CI), directed against N. meningitidis serogroups A, C, W and Y, by serum bactericidal assay using human complement (hSBA) at 1 month after one vaccination or two vaccinations of MenACWY-CRM given two months apart. Seroresponse is defined as: a. postvaccination hSBA titer ≥1:8 for subjects with a prevaccination hSBA titer <1:4; b. for subjects with a prevaccination hSBA ≥1:4, an increase of at least four times of the prevaccination hSBA titer. |
| Time Frame | One Month After Last Vaccination ( day 86) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on the primary per-protocol (PP) dataset, i.e. the subjects who received the vaccine correctly; provided evaluable serum samples at the relevant time points; and had no major protocol violations as defined prior to analysis. |
| Arm/Group Title | 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) |
|---|---|---|---|---|
| Arm/Group Description | Subjects 2-5 years of age received two MenACWY-CRM vaccinations | Subjects 2-5 years of age received one MenACWY-CRM vaccination | Subjects 6-10 years of age received two MenACWY-CRM vaccinations | Subjects 6-10 years of age received one MenACWY-CRM vaccination |
| Measure Participants | 136 | 144 | 153 | 142 |
| MenA(N=135,143,152,142) |
94
|
75
|
89
|
77
|
| MenC(N=131,140,149,142) |
92
|
65
|
93
|
73
|
| MenW(N=128,135,148,138) |
75
|
61
|
58
|
54
|
| MenY(N=128,133,148,142) |
91
|
64
|
89
|
60
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | Non-inferiority of seroresponse of two vaccinations vs.one vaccination for age cohort (2 to 5 years of age) for MenA | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Noninferiority was demonstrated for 2 to 5 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for MenA | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Group Differences at Day 86 |
| Estimated Value | 19 | |
| Confidence Interval |
(2-Sided) 97.5% 10 to 28.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | Non-inferiority of seroresponse of two vaccinations vs. one vaccination for age cohort (2 to 5 years of age) for MenC | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Noninferiority was demonstrated for 2 to 5 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for MenC | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Group Differences at Day 86 |
| Estimated Value | 27 | |
| Confidence Interval |
(2-Sided) 97.5% 16.9 to 37.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | Non-inferiority of seroresponse of two vaccinations vs. one vaccination for age cohort (2 to 5 years of age) for MenW | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Noninferiority was demonstrated for 2 to 5 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for MenW | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Group Differences at Day 86 |
| Estimated Value | 14 | |
| Confidence Interval |
(2-Sided) 97.5% 1.4 to 26.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | Non-inferiority of seroresponse of two vaccinations vs. one vaccination for age cohort (2 to 5 years of age) for MenY | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Noninferiority was demonstrated for 2 to 5 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for Men Y | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Group differences at Day 86 |
| Estimated Value | 27 | |
| Confidence Interval |
(2-Sided) 97.5% 15.6 to 37.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | 6 Through 10 Years (2 Vac), 6 Through 10 Years (1 Vac) |
|---|---|---|
| Comments | Non-inferiority of seroresponse of two vaccinations vs. one vaccination for age cohort (6 to 10 years of age) for MenA | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Noninferiority was demonstrated for 6 to 10 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for MenA | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccines Group Differences at Day 86 |
| Estimated Value | 11 | |
| Confidence Interval |
(2-Sided) 97.5% 1.7 to 21.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | 6 Through 10 Years (2 Vac), 6 Through 10 Years (1 Vac) |
|---|---|---|
| Comments | Non-inferiority of seroresponse of two vaccinations vs. one vaccination for age cohort (6 to 10 years of age) for MenC | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Noninferiority was demonstrated for 6 to 10 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for MenC | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccines Group differences at Day 86 |
| Estimated Value | 19 | |
| Confidence Interval |
(2-Sided) 97.5% 9.9 to 29.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | 6 Through 10 Years (2 Vac), 6 Through 10 Years (1 Vac) |
|---|---|---|
| Comments | Non-inferiority of seroresponse of two vaccinations vs. one vaccination for age cohort (6 to 10 years of age) for MenW | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Noninferiority was demonstrated for 6 to 10 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for MenW | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccines Group Differences at Day 86 |
| Estimated Value | 4 | |
| Confidence Interval |
(2-Sided) 97.5% -8.6 to 17.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | 6 Through 10 Years (2 Vac), 6 Through 10 Years (1 Vac) |
|---|---|---|
| Comments | Non-inferiority of seroresponse for two vaccinations vs. one vaccination for age cohort (6 to 10 years of age) for MenY | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Noninferiority was demonstrated for 6 to 10 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for MenY | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccines Group Differences at Day 86 |
| Estimated Value | 29 | |
| Confidence Interval |
(2-Sided) 97.5% 18.4 to 40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Superiority of Two Vaccinations Versus One Vaccination of MenACWY-CRM, by Age Cohort, as Measured by the Percentage of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroups A, C, W and Y, at 1 Month After Last Vaccination |
|---|---|
| Description | Immunogenicity was measured as the percentage of subjects with overall seroresponse and associated 2-sided 95% CI, directed against N. meningitidis serogroups A, C, W and Y, by hSBA at 1 month after one vaccination or two vaccinations of MenACWY-CRM. Seroresponse -postvaccination hSBA titer ≥1:8 for subjects with a prevaccination hSBA titer <1:4 and for subjects with a prevaccination hSBA ≥1:4, an increase of at least four times of the prevaccination hSBA titer. |
| Time Frame | One Month After Last Vaccination (day 86) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on the FAS dataset - All subjects in the exposed dataset who provided evaluable serum samples whose assay results were available for at least 1 serogroup on day 1 and 1 post baseline visit. |
| Arm/Group Title | 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) |
|---|---|---|---|---|
| Arm/Group Description | Subjects 2-5 years of age received two MenACWY-CRM vaccinations | Subjects 2-5 years of age received one MenACWY-CRM vaccination | Subjects 6-10 years of age received two MenACWY-CRM vaccinations | Subjects 6-10 years of age received one MenACWY-CRM vaccination |
| Measure Participants | 159 | 165 | 172 | 163 |
| MenA(N=158,163,171,163) |
95
|
77
|
89
|
79
|
| MenC(N=154,157,167,162) |
93
|
65
|
93
|
75
|
| MenW(N=150,154,167,159) |
75
|
61
|
57
|
52
|
| MenY(N=150,153,167,163) |
90
|
62
|
89
|
60
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | Superiority for age cohort (2 through 5 years of age) for MenA was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenA | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Group Differences at Day 86 |
| Estimated Value | 18 | |
| Confidence Interval |
(2-Sided) 98.75% 9.1 to 28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | Superiority for age cohort (2 through 5 years of age) for MenC was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenC | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Group Differences at Day 86 |
| Estimated Value | 28 | |
| Confidence Interval |
() 98.75% 17.1 to 38.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | Superiority for age cohort (2 through 5 years of age) for MenW was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenW | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Group differences at Day 86 |
| Estimated Value | 14 | |
| Confidence Interval |
(2-Sided) 98.75% 1 to 27.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | Superiority for age cohort (2 through 5 years of age) for MenY was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenY | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine groups Differences at Day 86 |
| Estimated Value | 28 | |
| Confidence Interval |
(2-Sided) 98.75% 16.2 to 39.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | 6 Through 10 Years (2 Vac), 6 Through 10 Years (1 Vac) |
|---|---|---|
| Comments | Superiority for age cohort (6 through 10 years of age) for MenA was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenA | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine groups differences at Day 86 |
| Estimated Value | 11 | |
| Confidence Interval |
(2-Sided) 98.75% 1 to 21.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | 6 Through 10 Years (2 Vac), 6 Through 10 Years (1 Vac) |
|---|---|---|
| Comments | Superiority for age cohort (6 through 10 years of age) for MenC was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenC | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Group differences at Day 86 |
| Estimated Value | 18 | |
| Confidence Interval |
(2-Sided) 97.5% 9.5 to 27.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | 6 Through 10 Years (2 Vac), 6 Through 10 Years (1 Vac) |
|---|---|---|
| Comments | Superiority for age cohort (6 through 10 years of age) for MenW was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenW | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Group Differences at Day 86 |
| Estimated Value | 5 | |
| Confidence Interval |
(2-Sided) 98.75% -8.4 to 18.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | 6 Through 10 Years (2 Vac), 6 Through 10 Years (1 Vac) |
|---|---|---|
| Comments | Superiority for age cohort (6 through 10 years of age) for MenY was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenY | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine group Differences at Day 86 |
| Estimated Value | 29 | |
| Confidence Interval |
(2-Sided) 98.75% 17 to 39.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Month After One or Two Vaccination(s) of MenACWY-CRM |
|---|---|
| Description | Immunogenicity was measured as the percentage of subjects who achieved hSBA titer ≥1:8 and associated 95% CI, at one month after one vaccination or two vaccinations of MenACWY-CRM. |
| Time Frame | One Month After Last Vaccination (day 86) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on the primary PP dataset. |
| Arm/Group Title | 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) |
|---|---|---|---|---|
| Arm/Group Description | Subjects 2-5 years of age received two MenACWY-CRM vaccinations | Subjects 2-5 years of age received one MenACWY-CRM vaccination | Subjects 6-10 years of age received two MenACWY-CRM vaccinations | Subjects 6-10 years of age received one MenACWY-CRM vaccination |
| Measure Participants | 136 | 144 | 153 | 142 |
| MenA(N=135,143,152,142) |
95
|
76
|
91
|
80
|
| MenC(N=131,140,149,142) |
98
|
76
|
99
|
89
|
| MenW(N=128,135,148,138) |
99
|
92
|
99
|
96
|
| MenY(N=128,133,148,142) |
96
|
69
|
96
|
73
|
| Title | Geometric Mean Titers of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Month After One or Two Vaccination(s) of MenACWY-CRM |
|---|---|
| Description | Immunogenicity was measured as hSBA geometric mean titers (GMTs) and 95% CI against N. meningitidis serogroups A, C, W and Y, one month after one vaccination or two vaccinations of MenACWY-CRM. |
| Time Frame | One Month After Last Vaccination (day 86) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on the primary PP dataset |
| Arm/Group Title | 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) |
|---|---|---|---|---|
| Arm/Group Description | Subjects 2-5 years of age received two MenACWY-CRM vaccinations | Subjects 2-5 years of age received one MenACWY-CRM vaccination | Subjects 6-10 years of age received two MenACWY-CRM vaccinations | Subjects 6-10 years of age received one MenACWY-CRM vaccination |
| Measure Participants | 136 | 144 | 153 | 142 |
| MenA(N=135,143,152,142) |
68
|
21
|
67
|
36
|
| MenC(N=131,140,149,142) |
146
|
22
|
165
|
67
|
| MenW(N=128,135,148,138) |
191
|
104
|
169
|
95
|
| MenY(N=128,133,148,142) |
70
|
15
|
76
|
26
|
| Title | Percentage of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Year After One or Two Vaccination(s) of MenACWY-CRM |
|---|---|
| Description | Immunogenicity was measured as the percentage of subjects with hSBA titer ≥1:8 and associated 95% CI at one year after one vaccination or two vaccinations of MenACWY-CRM. |
| Time Frame | One year after one vaccination or two vaccinations (day 422). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on the persistence PP dataset |
| Arm/Group Title | 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) |
|---|---|---|---|---|
| Arm/Group Description | Subjects 2-5 years of age received two MenACWY-CRM vaccinations | Subjects 2-5 years of age received one MenACWY-CRM vaccination | Subjects 6-10 years of age received two MenACWY-CRM vaccinations | Subjects 6-10 years of age received one MenACWY-CRM vaccination |
| Measure Participants | 136 | 144 | 153 | 142 |
| MenA(N=122,131,142,130) |
30
|
11
|
30
|
20
|
| MenC(N=123,128,141,130) |
61
|
41
|
81
|
55
|
| MenW(N=121,127,139,130) |
92
|
91
|
94
|
90
|
| MenY(N=121,122,140,130) |
67
|
57
|
75
|
65
|
| Title | Geometric Mean Titers of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Year After One or Two Vaccination(s) of MenACWY-CRM |
|---|---|
| Description | Immunogenicity was measured as hSBA GMTs and 95% CI against N. meningitidis serogroups A, C, W and Y at one year after one vaccination or two vaccinations of MenACWY-CRM. |
| Time Frame | One year after one vaccination or two vaccinations (day 422). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on the persistence PP dataset |
| Arm/Group Title | 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) |
|---|---|---|---|---|
| Arm/Group Description | Subjects 2-5 years of age received two MenACWY-CRM vaccinations | Subjects 2-5 years of age received one MenACWY-CRM vaccination | Subjects 6-10 years of age received two MenACWY-CRM vaccinations | Subjects 6-10 years of age received one MenACWY-CRM vaccination |
| Measure Participants | 136 | 144 | 153 | 142 |
| MenA(N=122,131,142,130) |
4.72
|
2.66
|
4.66
|
3.56
|
| MenC(N=123,128,141,130) |
10
|
7.03
|
24
|
15
|
| MenW(N=121,127,139,130) |
49
|
39
|
64
|
47
|
| MenY(N=121,122,140,130) |
14
|
9.88
|
20
|
13
|
| Title | Number of 2 to 5 Years-Old Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination |
|---|---|
| Description | Safety was assessed as the number of 2 to 5 years-old subjects who reported solicited local and systemic adverse events from day 1 up to and including day 7 after one or two vaccination(s) of MenACWY-CRM |
| Time Frame | From Days 1-7 after each vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on the safety dataset i.e. the subjects in the exposed population who provided postvaccination safety data. |
| Arm/Group Title | 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) |
|---|---|---|
| Arm/Group Description | Subjects 2-5 years of age received two MenACWY-CRM vaccinations | Subjects 2-5 years of age received one MenACWY-CRM vaccination |
| Measure Participants | 176 | 182 |
| Erythema(N=173,175) |
25
|
11
|
| Induration(N=173,175) |
19
|
7
|
| Tenderness (N=174,175) |
84
|
79
|
| Change in Eating Habits(N=173,175) |
26
|
30
|
| Sleepiness(N=173,175) |
49
|
46
|
| Irritability(N=173,175) |
51
|
50
|
| Body Temperature >=38.0(N=174,175) |
9
|
12
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced erythema in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 2.3 | |
| Confidence Interval |
(2-Sided) 95% 1.17 to 4.53 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced induration in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 2.75 | |
| Confidence Interval |
(2-Sided) 95% 1.18 to 6.36 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced tenderness in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.07 | |
| Confidence Interval |
(2-Sided) 95% 0.85 to 1.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced change in eating habits in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.88 | |
| Confidence Interval |
(2-Sided) 95% 0.54 to 1.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced sleepiness in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.08 | |
| Confidence Interval |
(2-Sided) 95% 0.76 to 1.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced irritability in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.03 | |
| Confidence Interval |
(2-Sided) 95% 0.74 to 1.43 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced fever (≥38 °C) in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.75 | |
| Confidence Interval |
(2-Sided) 95% 0.33 to 1.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Numbers of 6 to 10 Years-Old Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination |
|---|---|
| Description | Safety was assessed as the number of 6 to 10 years-old subjects who reported solicited local and systemic adverse events from day 1 up to and including day 7 after one or two vaccination(s) of MenACWY-CRM |
| Time Frame | From Days 1-7 after each vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on the safety dataset |
| Arm/Group Title | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) |
|---|---|---|
| Arm/Group Description | Subjects 6-10 years of age received two MenACWY-CRM vaccinations | Subjects 6-10 years of age received one MenACWY-CRM vaccination |
| Measure Participants | 180 | 175 |
| Erythema(N=178,166) |
23
|
15
|
| Induration(N=178,166) |
24
|
15
|
| Pain(N=178,166) |
106
|
78
|
| Loss of Appetite(N=177,166) |
27
|
14
|
| Nausea(N=177,165) |
29
|
21
|
| Fatigue(N=177,166) |
44
|
25
|
| Myalgia(N=177,165) |
63
|
43
|
| Arthralgia(N=177,165) |
20
|
9
|
| Headache(N=177,165) |
55
|
28
|
| Body Temperature>=38.0(N=178,166) |
11
|
9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced erythema in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.43 | |
| Confidence Interval |
(2-Sided) 95% 0.77 to 2.65 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced induration in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.49 | |
| Confidence Interval |
(2-Sided) 95% 0.81 to 2.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced pain in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.27 | |
| Confidence Interval |
(2-Sided) 95% 1.04 to 1.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced loss of appetite in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.81 | |
| Confidence Interval |
(2-Sided) 95% 0.98 to 3.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced nausea in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.29 | |
| Confidence Interval |
(2-Sided) 95% 0.77 to 2.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced fatigue in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.65 | |
| Confidence Interval |
(2-Sided) 95% 1.06 to 2.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced myalgia in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.37 | |
| Confidence Interval |
(2-Sided) 95% 0.99 to 1.89 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced arthralgia in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 2.07 | |
| Confidence Interval |
(2-Sided) 95% 0.97 to 4.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced headache in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.83 | |
| Confidence Interval |
(2-Sided) 95% 1.22 to 2.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | 2 Through 5 Years (2 Vac), 2 Through 5 Years (1 Vac) |
|---|---|---|
| Comments | The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced fever (≥38 °C) in the two doses versus in the one dose of MenACWY-CRM | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.14 | |
| Confidence Interval |
(2-Sided) 95% 0.48 to 2.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Subjects Who Reported Selected AEs After Any Vaccination |
|---|---|
| Description | Safety was assessed as the number subjects who reported Selected AEs from day 1 up to day 86 after one or two vaccination(s) of MenACWY-CRM |
| Time Frame | Day 1 to Day 86 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on Safety Set Unsolicited AEs |
| Arm/Group Title | 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) |
|---|---|---|---|---|
| Arm/Group Description | Subjects 2-5 years of age received two MenACWY-CRM vaccinations | Subjects 2-5 years of age received one MenACWY-CRM vaccination | Subjects 6-10 years of age received two MenACWY-CRM vaccinations | Subjects 6-10 years of age received one MenACWY-CRM vaccination |
| Measure Participants | 179 | 179 | 181 | 174 |
| SAEs |
1
|
0
|
0
|
0
|
| At least possibly related SAEs |
0
|
0
|
0
|
0
|
| Medically attended AEs |
50
|
55
|
46
|
46
|
| At least possibly related medically attended AEs |
0
|
3
|
1
|
1
|
| AEs resulting in premature withdrawal |
0
|
0
|
0
|
1
|
| Deaths |
0
|
0
|
0
|
0
|
| Title | Number of Subjects Who Reported Selected AEs After Any Vaccination |
|---|---|
| Description | Safety was assessed as the number subjects who reported Selected AEs from day 1 up to day 422 after one or two vaccination(s) of MenACWY-CRM |
| Time Frame | Day 1 to Day 422 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on safety set |
| Arm/Group Title | 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) |
|---|---|---|---|---|
| Arm/Group Description | Subjects 2-5 years of age received two MenACWY-CRM vaccinations | Subjects 2-5 years of age received one MenACWY-CRM vaccination | Subjects 6-10 years of age received two MenACWY-CRM vaccinations | Subjects 6-10 years of age received one MenACWY-CRM vaccination |
| Measure Participants | 179 | 179 | 181 | 174 |
| Medically attended AEs |
103
|
101
|
95
|
97
|
| At least possibly related medically attended AEs |
1
|
4
|
1
|
2
|
| AEs resulting in premature withdrawal |
0
|
0
|
0
|
1
|
| SAEs |
2
|
1
|
1
|
1
|
| Deaths |
0
|
0
|
0
|
0
|
Adverse Events
| Time Frame | Throughout study period | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Serious adverse events (SAEs) were collected from day 1 to study termination/early termination. | |||||||||
| Arm/Group Title | 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) | Total | |||||
| Arm/Group Description | Subjects 2-5 years of age received two MenACWY-CRM vaccinations | Subjects 2-5 years of age received one MenACWY-CRM vaccination | Subjects 6-10 years of age received two MenACWY-CRM vaccinations | Subjects 6-10 years of age received one MenACWY-CRM vaccination | Total Population | |||||
All Cause Mortality |
||||||||||
| 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) | Total | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||
Serious Adverse Events |
||||||||||
| 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) | Total | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/179 (1.1%) | 1/179 (0.6%) | 1/181 (0.6%) | 1/174 (0.6%) | 5/713 (0.7%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| IMMUNE THROMBOCYTOPENIC PURPURA | 0/179 (0%) | 1/179 (0.6%) | 0/181 (0%) | 0/174 (0%) | 1/713 (0.1%) | |||||
| Infections and infestations | ||||||||||
| OTITIS MEDIA | 1/179 (0.6%) | 0/179 (0%) | 0/181 (0%) | 0/174 (0%) | 1/713 (0.1%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| DEHYDRATION | 1/179 (0.6%) | 0/179 (0%) | 0/181 (0%) | 0/174 (0%) | 1/713 (0.1%) | |||||
| Nervous system disorders | ||||||||||
| PETIT MAL EPILEPSY | 1/179 (0.6%) | 0/179 (0%) | 0/181 (0%) | 0/174 (0%) | 1/713 (0.1%) | |||||
| Psychiatric disorders | ||||||||||
| INTERMITTENT EXPLOSIVE DISORDER | 0/179 (0%) | 0/179 (0%) | 0/181 (0%) | 1/174 (0.6%) | 1/713 (0.1%) | |||||
| OPPOSITIONAL DEFIANT DISORDER | 0/179 (0%) | 0/179 (0%) | 0/181 (0%) | 1/174 (0.6%) | 1/713 (0.1%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| ASTHMA | 0/179 (0%) | 0/179 (0%) | 1/181 (0.6%) | 0/174 (0%) | 1/713 (0.1%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| DERMATITIS ALLERGIC | 1/179 (0.6%) | 0/179 (0%) | 0/181 (0%) | 0/174 (0%) | 1/713 (0.1%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| 2 Through 5 Years (2 Vac) | 2 Through 5 Years (1 Vac) | 6 Through 10 Years (2 Vac) | 6 Through 10 Years (1 Vac) | Total | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 148/179 (82.7%) | 142/179 (79.3%) | 153/181 (84.5%) | 133/174 (76.4%) | 576/713 (80.8%) | |||||
| Gastrointestinal disorders | ||||||||||
| ABDOMINAL PAIN UPPER | 4/179 (2.2%) | 6/179 (3.4%) | 5/181 (2.8%) | 9/174 (5.2%) | 24/713 (3.4%) | |||||
| DIARRHOEA | 8/179 (4.5%) | 10/179 (5.6%) | 5/181 (2.8%) | 5/174 (2.9%) | 28/713 (3.9%) | |||||
| NAUSEA | 0/179 (0%) | 0/179 (0%) | 29/181 (16%) | 23/174 (13.2%) | 52/713 (7.3%) | |||||
| VOMITING | 19/179 (10.6%) | 19/179 (10.6%) | 15/181 (8.3%) | 11/174 (6.3%) | 64/713 (9%) | |||||
| General disorders | ||||||||||
| FATIGUE | 1/179 (0.6%) | 1/179 (0.6%) | 47/181 (26%) | 32/174 (18.4%) | 81/713 (11.4%) | |||||
| INJECTION SITE ERYTHEMA | 71/179 (39.7%) | 48/179 (26.8%) | 64/181 (35.4%) | 49/174 (28.2%) | 232/713 (32.5%) | |||||
| INJECTION SITE INDURATION | 54/179 (30.2%) | 39/179 (21.8%) | 60/181 (33.1%) | 40/174 (23%) | 193/713 (27.1%) | |||||
| INJECTION SITE PAIN | 93/179 (52%) | 91/179 (50.8%) | 120/181 (66.3%) | 88/174 (50.6%) | 392/713 (55%) | |||||
| PYREXIA | 29/179 (16.2%) | 34/179 (19%) | 26/181 (14.4%) | 26/174 (14.9%) | 115/713 (16.1%) | |||||
| Infections and infestations | ||||||||||
| CONJUNCTIVITIS | 7/179 (3.9%) | 11/179 (6.1%) | 1/181 (0.6%) | 3/174 (1.7%) | 22/713 (3.1%) | |||||
| EAR INFECTION | 15/179 (8.4%) | 6/179 (3.4%) | 5/181 (2.8%) | 3/174 (1.7%) | 29/713 (4.1%) | |||||
| NASOPHARYNGITIS | 2/179 (1.1%) | 11/179 (6.1%) | 4/181 (2.2%) | 4/174 (2.3%) | 21/713 (2.9%) | |||||
| OTITIS MEDIA | 19/179 (10.6%) | 24/179 (13.4%) | 7/181 (3.9%) | 8/174 (4.6%) | 58/713 (8.1%) | |||||
| PHARYNGITIS | 16/179 (8.9%) | 16/179 (8.9%) | 18/181 (9.9%) | 6/174 (3.4%) | 56/713 (7.9%) | |||||
| PHARYNGITIS STREPTOCOCCAL | 12/179 (6.7%) | 18/179 (10.1%) | 17/181 (9.4%) | 14/174 (8%) | 61/713 (8.6%) | |||||
| SINUSITIS | 8/179 (4.5%) | 12/179 (6.7%) | 6/181 (3.3%) | 8/174 (4.6%) | 34/713 (4.8%) | |||||
| UPPER RESPIRATORY TRACT INFECTION | 22/179 (12.3%) | 21/179 (11.7%) | 13/181 (7.2%) | 16/174 (9.2%) | 72/713 (10.1%) | |||||
| VIRAL INFECTION | 9/179 (5%) | 13/179 (7.3%) | 7/181 (3.9%) | 4/174 (2.3%) | 33/713 (4.6%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| DECREASED APPETITE | 1/179 (0.6%) | 1/179 (0.6%) | 27/181 (14.9%) | 16/174 (9.2%) | 45/713 (6.3%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| ARTHRALGIA | 0/179 (0%) | 0/179 (0%) | 22/181 (12.2%) | 13/174 (7.5%) | 35/713 (4.9%) | |||||
| MYALGIA | 0/179 (0%) | 0/179 (0%) | 66/181 (36.5%) | 48/174 (27.6%) | 114/713 (16%) | |||||
| Nervous system disorders | ||||||||||
| HEADACHE | 6/179 (3.4%) | 8/179 (4.5%) | 62/181 (34.3%) | 38/174 (21.8%) | 114/713 (16%) | |||||
| SOMNOLENCE | 54/179 (30.2%) | 48/179 (26.8%) | 0/181 (0%) | 1/174 (0.6%) | 103/713 (14.4%) | |||||
| Psychiatric disorders | ||||||||||
| EATING DISORDER | 26/179 (14.5%) | 30/179 (16.8%) | 0/181 (0%) | 0/174 (0%) | 56/713 (7.9%) | |||||
| IRRITABILITY | 55/179 (30.7%) | 51/179 (28.5%) | 1/181 (0.6%) | 1/174 (0.6%) | 108/713 (15.1%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| COUGH | 22/179 (12.3%) | 17/179 (9.5%) | 12/181 (6.6%) | 15/174 (8.6%) | 66/713 (9.3%) | |||||
| RHINITIS ALLERGIC | 2/179 (1.1%) | 10/179 (5.6%) | 3/181 (1.7%) | 1/174 (0.6%) | 16/713 (2.2%) | |||||
| RHINORRHOEA | 14/179 (7.8%) | 9/179 (5%) | 3/181 (1.7%) | 5/174 (2.9%) | 31/713 (4.3%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 877-379-3718 |
| GSKClinicalSupportHD@gsk.com |
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01682876
Other Study ID Numbers:
- 205238
- V59_57
- 2011-004421-27
First Posted:
Sep 11, 2012
Last Update Posted:
Jun 14, 2019
Last Verified:
Jun 1, 2019