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.
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 |
v3(current) |
This version publication date |
08 Oct 2021
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First version publication date |
04 Apr 2015
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Other versions |
v1 (removed from public view) , v2 |
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 |
France: 155
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Country: Number of subjects enrolled |
Germany: 259
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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 |
Healthy male or female subjects between, and including 2 and 10 years of age, intramuscularly received 1 dose of Nimenrix vaccine into the non-dominant deltoid 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 |
Healthy male or female subjects between, and including 2 and 10 years of age, intramuscularly received 1 dose of Menjugate vaccine into the non-dominant 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 |
Healthy male or female subjects between, and including 2 and 10 years of age, intramuscularly received 1 dose of Nimenrix vaccine into the non-dominant deltoid region, at Day 0. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Menjugate Group
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Reporting group description |
Healthy male or female subjects between, and including 2 and 10 years of age, intramuscularly received 1 dose of Menjugate vaccine into the non-dominant 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 |
Healthy male or female subjects between, and including 2 and 10 years of age, intramuscularly received 1 dose of Nimenrix vaccine into the non-dominant deltoid region, at Day 0. | ||
Reporting group title |
Menjugate Group
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Reporting group description |
Healthy male or female subjects between, and including 2 and 10 years of age, intramuscularly received 1 dose of Menjugate vaccine into the non-dominant thigh region, at Day 0. |
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End point title |
Number of subjects with vaccine response to meningococcal serogroup C serum based on a bactericidal assay using baby rabbit complement (rSBA-MenC) antibody | ||||||||||||
End point description |
Vaccine response to MenC was defined as: -for initially seronegative subjects [i.e. rSBA-MenC titer below (<) 1:8], antibody titer greater than or equal to (≥) 1:32; -for initially seropositive (i.e. rSBA-MenC titer ≥ 1:8), antibody titer post-vaccination ≥ 4-fold the pre-vaccination antibody titer.
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End point type |
Primary
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End point timeframe |
One month after the vaccination (Month 1)
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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% confidence interval (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 serogroup A (rSBA) antibody titers by serogroup | ||||||||||||||||||||||||||||||||||||
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 (Month 0) and one month after vaccination (Month 1)
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No statistical analyses for this end point |
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End point title |
Anti-meningococcal serogroup polysaccharide (anti-PS) antibody concentrations | ||||||||||||||||||||||||||||||||||||
End point description |
Anti-PSA, anti-PSC, anti-PSW-135 and anti-PSY 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 (Month 0) and one month after vaccination (Month 1)
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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 and Grade 3 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. Grade 3 Pain = cried when limb was moved/spontaneously painful. Grade 3 Redness and Swelling= redness/swelling spreading beyond (>) 30 millimeters (mm).
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End point type |
Secondary
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End point timeframe |
During the 4-day (Day 0-Day 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 and Grade 3 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. Grade 3 Pain = pain that prevented normal activity. Grade 3 Redness and Swelling= redness/swelling spreading beyond (>) 50 millimeters (mm).
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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, Grade 3 and related solicited general symptoms | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited general symptoms assessed were drowsiness, fever[defined as oral temperature ≥ 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of the general symptom regardless of intensity grade and relationship to vaccination. Grade 3 Symptom = symptom that prevented normal activity. Grade 3 Loss of appetite = did not eat at all. Grade 3 Fever = fever > 39.5°C. Related = general symptoms assessed by the investigator as causally related to vaccination.
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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, Grade 3 and related solicited general symptoms | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited general symptoms assessed were fatigue, fever(defined as oral temperature ≥ 37.5 °C), gastrointestinal and headache. Any = occurrence of the general symptom regardless of intensity grade and relationship to vaccination. Grade 3 Symptom = symptom that prevented normal activity. Grade 3 Loss of appetite = did not eat at all. Grade 3 Fever = fever > 39.5°C. Related = general symptoms assessed by the investigator as causally related to vaccination.
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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(AEs) | ||||||||||||||||||
End point description |
Specific AEs included: - rash (hives, idiopathic thrombocytopenic purpura, petechiae); - new onset of chronic illness(es) (NOCI) (e.g. autoimmune disorders, asthma, type I diabetes and allergies); - 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 (Month 6)
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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 |
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
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End point type |
Secondary
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End point timeframe |
Up to one month (Day 0-Day 30) 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 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 |
Up to six months after vaccination (Month 6)
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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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Adverse event reporting additional description |
The solicited local and general symptoms were only collected from those subjects who filled in their symptom sheets.
The number of occurrences reported for solicited symptoms, AEs, and SAEs was not available for posting. The number of subjects affected by each specific event was indicated as the number of occurrences.
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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 solicited local and general symptoms were only collected from those subjects who filled in their symptom sheets. [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 solicited local and general symptoms were only collected from those subjects who filled in their symptom sheets. [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 solicited local and general symptoms were only collected from those subjects who filled in their symptom sheets. [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 solicited local and general symptoms were only collected from those subjects who filled in their symptom sheets. This solicited general symptom was assessed only for subjects between 2 to 5 years of age, from the two groups. [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 solicited local and general symptoms were only collected from those subjects who filled in their symptom sheets. [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 solicited local and general symptoms were only collected from those subjects who filled in their symptom sheets. This solicited general symptom was assessed only for subjects between 2 to 5 years of age, from the two groups. [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 solicited local and general symptoms were only collected from those subjects who filled in their symptom sheets. This solicited general symptom was assessed only for subjects between 2 to 5 years of age, from the two groups. [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 solicited local and general symptoms were only collected from those subjects who filled in their symptom sheets. This solicited general symptom was assessed only for subjects between 6 to 10 years of age, from the two groups. [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 solicited local and general symptoms were only collected from those subjects who filled in their symptom sheets. This solicited general symptom was assessed only for subjects between 6 to 10 years of age, from the two groups. [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 solicited local and general symptoms were only collected from those subjects who filled in their symptom sheets. This solicited general symptom was assessed only for subjects between 6 to 10 years of age, from the two groups. |
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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 |