Clinical Trial Results:
A phase III, open, randomized, controlled, primary vaccination study to demonstrate non-inferiority of GlaxoSmithKline (GSK) Biologicals’ meningococcal serogroup ACWY conjugate vaccine compared to licensed MenC-CRM197 conjugate vaccine when administered to healthy subjects aged 2 through 10 years.
Due to a system error, the data reported in v1 is not correct and has been removed from public view.
Summary
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EudraCT number |
2007-007837-38 |
Trial protocol |
DE FR |
Global end of trial date |
08 Jan 2009
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Results information
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Results version number |
v2 |
This version publication date |
08 Jun 2016
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First version publication date |
04 Apr 2015
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Other versions |
v1 (removed from public view) , v3 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
111414
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00674583 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GlaxoSmithKline Biologicals
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Sponsor organisation address |
Rue de l'Institut 89, Rixensart, Belgium, B-1330
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Public contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals , 044 2089904466, GSKClinicalSupportHD@gsk.com
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Scientific contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals , 044 2089904466, GSKClinicalSupportHD@gsk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000429-PIP01-01 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 May 2009
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 Sep 2008
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Jan 2009
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
One month after vaccination:
•To demonstrate non-inferiority of the MenACWY-TT conjugate vaccine compared to the licensed conjugate vaccine (MenC-CRM197) in terms of serum bactericidal antibody vaccine response to N. meningitidis serogroup C (MenC).
Criterion for assessment of non-inferiority for serogroup C:
The lower limit of the two-sided standardized asymptotic 95% confidence interval (CI) for the group difference (MenACWY-TT Group minus MenC-CRM Group) in the percentages of subjects with vaccine response to meningococcal polysaccharide C serum based on a bactericidal assay using baby rabbit complement (rSBA-MenC) is greater than or equal to the pre-defined clinical limit of –10%.
The vaccine response to MenC is defined as post-vaccination rSBA-MenC titer ≥ 1:32 for initially seronegative subjects (i.e. rSBA-MenC titer < 1:8) and at least a 4-fold increase in rSBA-MenC titers from pre to post-vaccination for initially seropositive (i.e. rSBA-MenC titer ≥ 1:8) subjects.
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Protection of trial subjects |
Written informed consent was obtained from each subject’s parent/guardian prior to the performance of any study-specific procedures.The investigator was required to notify GSK Biologicals’ Study Contact for Serious Adverse Event by fax, within 24 hours of his/her becoming aware of the SAE. After the initial AE/SAE report, the investigator was required to proactively follow each subject and provide further information to GSK Biologicals on the subject’s condition.
All AEs and SAEs documented at a previous visit/contact and designated as not recovered/not resolved or recovering/resolving were reviewed at subsequent visits/contacts.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 May 2008
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 259
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Country: Number of subjects enrolled |
France: 155
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Worldwide total number of subjects |
414
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EEA total number of subjects |
414
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
414
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||
Pre-assignment
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Screening details |
During the screening the following steps occurred: check for inclusion/exclusion criteria,contraindications/precautions, medical history of the subjects and signing informed consent forms | |||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Nimenrix Group | |||||||||
Arm description |
Subjects received 1 dose of Nimenrix vaccine administered intramuscularly in the non-dominant deltoid/thigh region at Day 0. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Nimenrix
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Investigational medicinal product code |
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Other name |
MenACWY-TT, Meningococcal vaccine GSK134612
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Pharmaceutical forms |
Powder and solvent for solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
1 dose by intramuscular administration in the non-dominant deltoid/thigh region at Day 0.
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Arm title
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Menjugate Group | |||||||||
Arm description |
Subjects received 1 dose of Menjugate vaccine administered intramuscularly in the non-dominant deltoid/thigh region at Day 0. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Menjugate
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Investigational medicinal product code |
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Other name |
MenC-CRM197
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Pharmaceutical forms |
Powder and solvent for solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
1 dose by intramuscular administration in the non-dominant deltoid/thigh region at Day 0.
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Baseline characteristics reporting groups
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Reporting group title |
Nimenrix Group
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Reporting group description |
Subjects received 1 dose of Nimenrix vaccine administered intramuscularly in the non-dominant deltoid/thigh region at Day 0. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Menjugate Group
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Reporting group description |
Subjects received 1 dose of Menjugate vaccine administered intramuscularly in the non-dominant deltoid/thigh region at Day 0. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Nimenrix Group
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Reporting group description |
Subjects received 1 dose of Nimenrix vaccine administered intramuscularly in the non-dominant deltoid/thigh region at Day 0. | ||
Reporting group title |
Menjugate Group
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Reporting group description |
Subjects received 1 dose of Menjugate vaccine administered intramuscularly in the non-dominant deltoid/thigh region at Day 0. |
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End point title |
Number of subjects with vaccine response to rSBA-MenC antibody | ||||||||||||
End point description |
Vaccine response to MenC was defined as the number of subjects with post-vaccination rSBA-MenC titer ≥ 1:32 for initially seronegative subjects (i.e. rSBA-MenC titer < 1:8) and at least a 4-fold increase in rSBA-MenC titers from pre to post-vaccination for initially seropositive (i.e. rSBA-MenC titer ≥ 1:8) subjects.
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End point type |
Primary
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End point timeframe |
One month after the vaccination
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Statistical analysis title |
Difference in % of subjects with vaccine response | ||||||||||||
Statistical analysis description |
To demonstrate the non-inferiority of the Nimenrix group compared to the Menjugate group, two-sided standardized asymptotic 95% CI for the groups difference [Nimenrix group minus Menjugate group] in the percentages of subjects with bactericidal vaccine response to MenC was computed.
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Comparison groups |
Nimenrix Group v Menjugate Group
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Number of subjects included in analysis |
360
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||
Method |
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Parameter type |
Difference in percentage | ||||||||||||
Point estimate |
-0.88
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-5.25 | ||||||||||||
upper limit |
5.75 | ||||||||||||
Notes [1] - For MenC serogroup, the two-sided standardized asymptotic 95% CI for the group difference (Nimenrix Group minus Menjugate Group) in the percentages of subjects with bactericidal vaccine response was computed. |
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End point title |
Meningococcal serogroups rSBA antibody titers | ||||||||||||||||||||||||||||||||||||
End point description |
Antibody titers were expressed as geometric mean titers (GMTs).
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End point type |
Secondary
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End point timeframe |
Prior to and one month after vaccination
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No statistical analyses for this end point |
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End point title |
Anti-meningococcal serotype polysaccharide (anti-PS) antibody concentrations | ||||||||||||||||||||||||||||||||||||
End point description |
Antibody concentrations were expressed as geometric mean concentrations (GMCs) and tabulated as micrograms per milliliter (μg/mL).
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End point type |
Secondary
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End point timeframe |
Prior to and one month after vaccination
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No statistical analyses for this end point |
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End point title |
Number of subjects between 2 and 5 years of age with any solicited local symptoms | ||||||||||||||||||
End point description |
Solicited symptoms assessed were: pain, redness and swelling. Any = occurrence of any local symptom regardless of their intensity grade.
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End point type |
Secondary
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End point timeframe |
During the 4-day (Day 0-Day 3) follow-up period after vaccination
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No statistical analyses for this end point |
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End point title |
Number of subjects between 6 and 10 years of age with any solicited local symptoms | ||||||||||||||||||
End point description |
Solicited symptoms assessed were: pain, redness and swelling. Any = occurrence of any local symptom regardless of their intensity grade.
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End point type |
Secondary
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End point timeframe |
During the 4-day (Days 0-3) post-vaccination period
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No statistical analyses for this end point |
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End point title |
Number of subjects between 2 and 5 years of age with any solicited general symptoms | |||||||||||||||||||||
End point description |
Solicited general symptoms assessed were drowsiness, fever, irritability and loss of appetite. Any = occurrence of the general symptom regardless of intensity grade and relationship to vaccination. Any fever = oral temperature ≥ 37.5°C.
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End point type |
Secondary
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End point timeframe |
During the 4-day (Days 0-3) post-vaccination period
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No statistical analyses for this end point |
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End point title |
Number of subjects between 6 and 10 years of age with any solicited general symptoms | |||||||||||||||||||||
End point description |
Solicited general symptoms assessed were fatigue, fever, gastrointestinal and headache. Any = occurrence of the general symptom regardless of intensity grade and relationship to vaccination. Any fever = oral temperature ≥ 37.5°C
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End point type |
Secondary
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End point timeframe |
During the 4-day (Days 0-3) post-vaccination period
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No statistical analyses for this end point |
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End point title |
Number of subjects reporting specific adverse events | ||||||||||||||||||
End point description |
Specific AEs include:
− rash (hives, idiopathic thrombocytopenic purpura, petechiae),
− new onset of chronic illness(es) (NOCI) (e.g. autoimmune disorders, asthma, type I diabetes and allergies),
and/or
− conditions prompting emergency room (ER) visits.
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End point type |
Secondary
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End point timeframe |
Up to 6 months after vaccination
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No statistical analyses for this end point |
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End point title |
Number of subjects reporting any unsolicited adverse events (AEs) | ||||||||||||
End point description |
Unsolicited symptom covers any symptom reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
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End point type |
Secondary
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End point timeframe |
Up to one month (Day 0-Day 30) after vaccination
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No statistical analyses for this end point |
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End point title |
Number of subjects reporting any serious adverse events (SAEs) | ||||||||||||
End point description |
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
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End point type |
Secondary
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End point timeframe |
From Day 0 up to 6 months after vaccination
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Serious adverse events: from Day 0 up to 6 months after vaccination. Solicited symptoms: during the 4-day (Day 0-Day 3) follow-up period after vaccination. Unsolicited adverse events: Up to one month (Day 0-Day 30) after vaccination.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.1
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Reporting groups
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Reporting group title |
Menjugate Group
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Reporting group description |
Subjects received 1 dose of Menjugate vaccine administered intramuscularly in the non-dominant deltoid/thigh region at Day 0. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Nimenrix Group
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Reporting group description |
Subjects received 1 dose of Nimenrix vaccine administered intramuscularly in the non-dominant deltoid/thigh region at Day 0. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Notes [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheets completed. [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheets completed. [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheets completed. [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheets completed. [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheets completed. [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheets completed. [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheets completed. [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheets completed. [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheets completed. [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheets completed. [11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheets completed. [12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheets completed. [13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheets completed. [14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheets completed. |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |