Clinical Trial Results:
A phase III, open, controlled study to assess the persistence of antibodies after one dose of GlaxoSmithKline Biologicals’ meningococcal serogroup ACWY conjugate vaccine (MenACWY-TT) given intramuscularly versus one dose of Mencevax™ ACWY given subcutaneously to healthy subjects aged 11 through 17 years in the primary study 109069 (MenACWY-TT-036)
Summary
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EudraCT number |
2012-005641-21 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
17 May 2013
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Results information
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Results version number |
v2(current) |
This version publication date |
07 Apr 2016
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First version publication date |
17 Jul 2015
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Other versions |
v1 |
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 |
112148
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00974363 | ||
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 2089-904466, GSKClinicalSupportHD@gsk.com
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Scientific contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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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 |
30 Jun 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 May 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
17 May 2013
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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 |
At 24, 36, 48, and 60 months after primary vaccination of adolescents with Nimenrix™ or Mencevax™ ACWY vaccine:
• To evaluate the persistence of meningococcal antibodies in terms of percentage of subjects with serum bactericidal antibodies using baby rabbit complement (rSBA) titres ≥ 1:8 for each of the 4 serogroups.
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Protection of trial subjects |
Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects that had no contraindications to any components of the vaccines.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Sep 2009
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
5 Years | ||
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 |
Philippines: 388
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Country: Number of subjects enrolled |
India: 309
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Worldwide total number of subjects |
697
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EEA total number of subjects |
0
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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) |
0
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Adolescents (12-17 years) |
697
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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. | |||||||||
Pre-assignment period milestones
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Number of subjects started |
697 | |||||||||
Number of subjects completed |
689 | |||||||||
Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
No vaccination received: 8 | |||||||||
Period 1
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Period 1 title |
Month 24 (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 vaccinated with a single dose of MenACWY-TT vaccine, in the primary study 109069 (NCT00464815). | |||||||||
Arm type |
No Intervention | |||||||||
Investigational medicinal product name |
Nimenrix™
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Investigational medicinal product code |
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Other name |
MenACWY-TT
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Pharmaceutical forms |
Injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
MenACWY-TT vaccine was administered by intramuscular injection in the deltoid region of the nondominant
arm.
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Arm title
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Mencevax Group | |||||||||
Arm description |
Subjects vaccinated with a single dose of MenACWY vaccine, in the primary study 109069 (NCT00464815). | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: No vaccination was received for 8 subjects, hence they were excluded from the study. |
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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 vaccinated with a single dose of MenACWY-TT vaccine, in the primary study 109069 (NCT00464815). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Mencevax Group
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Reporting group description |
Subjects vaccinated with a single dose of MenACWY vaccine, in the primary study 109069 (NCT00464815). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 vaccinated with a single dose of MenACWY-TT vaccine, in the primary study 109069 (NCT00464815). | ||
Reporting group title |
Mencevax Group
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Reporting group description |
Subjects vaccinated with a single dose of MenACWY vaccine, in the primary study 109069 (NCT00464815). |
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End point title |
Number of subjects with Meningitis A antibody titres by serum bactericidal assay (using rabbit complement) (rSBA-MenA) ≥1:8 [1] | |||||||||||||||||||||
End point description |
These analyses were performed by the Public Health England (PHE) laboratory and by GSK Biologicals’ laboratory
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End point type |
Primary
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End point timeframe |
At months 24, 36, 48 and 60 post primary dose
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted. |
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No statistical analyses for this end point |
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End point title |
Number of subjects with rSBA-MenC antibody titres ≥1:8 [2] | |||||||||||||||||||||
End point description |
These analyses were performed by the Public Health England (PHE) laboratory and by GSK Biologicals’ laboratory
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End point type |
Primary
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End point timeframe |
At months 24, 36, 48 and 60 post primary dose
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted. |
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No statistical analyses for this end point |
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End point title |
Number of subjects with rSBA-MenW-135 antibody titres ≥1:8 [3] | |||||||||||||||||||||
End point description |
These analyses were performed by the Public Health England (PHE) laboratory and by GSK Biologicals’ laboratory
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End point type |
Primary
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End point timeframe |
At months 24, 36, 48 and 60 post primary dose
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted. |
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No statistical analyses for this end point |
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End point title |
Number of subjects with rSBA-MenY antibody titres ≥1:8 [4] | |||||||||||||||||||||
End point description |
These analyses were performed by the Public Health England (PHE) laboratory and by GSK Biologicals’ laboratory
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End point type |
Primary
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End point timeframe |
At months 24, 36, 48 and 60 post primary dose
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted. |
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No statistical analyses for this end point |
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End point title |
Number of subjects with rSBA-MenA antibody titres ≥1:128 | |||||||||||||||||||||
End point description |
These analyses were performed by the Public Health England (PHE) laboratory and by GSK Biologicals’ laboratory
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End point type |
Secondary
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End point timeframe |
At months 24, 36, 48 and 60 post primary dose
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No statistical analyses for this end point |
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End point title |
Number of subjects with rSBA-MenC antibody titres ≥1:128 | |||||||||||||||||||||
End point description |
These analyses were performed by the Public Health England (PHE) laboratory and by GSK Biologicals’ laboratory
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End point type |
Secondary
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End point timeframe |
At months 24, 36, 48 and 60 post primary dose
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No statistical analyses for this end point |
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End point title |
Number of subjects with rSBA-MenW-135 antibody titres ≥1:128 | |||||||||||||||||||||
End point description |
These analyses were performed by the Public Health England (PHE) laboratory and by GSK Biologicals’ laboratory
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End point type |
Secondary
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End point timeframe |
At months 24, 36, 48 and 60 post primary dose
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No statistical analyses for this end point |
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End point title |
Number of subjects with rSBA-MenY antibody titres ≥1:128 | |||||||||||||||||||||
End point description |
These analyses were performed by the Public Health England (PHE) laboratory and by GSK Biologicals’ laboratory
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End point type |
Secondary
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End point timeframe |
At months 24, 36, 48 and 60 post primary dose
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No statistical analyses for this end point |
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End point title |
Antibody titers for rSBA-MenA | ||||||||||||||||||||||||
End point description |
These analyses were performed by the Public Health England (PHE) laboratory and by GSK Biologicals’ laboratory
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End point type |
Secondary
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End point timeframe |
At months 24, 36, 48 and 60 post primary dose
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No statistical analyses for this end point |
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End point title |
Antibody titers for rSBA-MenC | ||||||||||||||||||||||||
End point description |
These analyses were performed by the Public Health England (PHE) laboratory and by GSK Biologicals’ laboratory
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End point type |
Secondary
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End point timeframe |
At months 24, 36, 48 and 60 post primary dose
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No statistical analyses for this end point |
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End point title |
Antibody titers for rSBA-MenW-135 | ||||||||||||||||||||||||
End point description |
These analyses were performed by the Public Health England (PHE) laboratory and by GSK Biologicals’ laboratory
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End point type |
Secondary
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End point timeframe |
At months 24, 36, 48 and 60 post primary dose
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No statistical analyses for this end point |
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End point title |
Antibody titers for rSBA-MenY | ||||||||||||||||||||||||
End point description |
These analyses were performed by the Public Health England (PHE) laboratory and by GSK Biologicals’ laboratory
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End point type |
Secondary
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End point timeframe |
At months 24, 36, 48 and 60 post primary dose
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No statistical analyses for this end point |
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End point title |
Number of subjects with anti-polysaccharide A (anti-PSA), anti-polysaccharide C (anti-PSC), anti-polysaccharide W-135 (anti-PSW-135) and anti-polysaccharide Y (anti-PSY) antibody concentrations equal to or above the cut-off values | |||||||||||||||||||||||||||||||||
End point description |
These analyses were performed by the GSK Biologicals’ laboratory
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End point type |
Secondary
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End point timeframe |
At month 24
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No statistical analyses for this end point |
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End point title |
Concentrations of anti-PSA, anti-PSC, anti-PSW-135 and anti-PSY antibodies | ||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At month 24
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No statistical analyses for this end point |
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End point title |
Number of subjects with serious adverse events (SAEs) | |||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At months 24, 36, 48 and 60
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Serious adverse events (SAEs): up to Month 24, 36, 48 and 60.
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Assessment type |
Non-systematic | |||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||
Dictionary version |
18.0
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Reporting groups
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Reporting group title |
Mencevax Group
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Reporting group description |
Subjects vaccinated with a single dose of MenACWY vaccine. | |||||||||||||||
Reporting group title |
Nimenrix Group
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Reporting group description |
Subjects vaccinated with a single dose of MenACWY-TT vaccine. | |||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||
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Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No information about unsolicited AEs was collected during this study as no product was administered. |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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15 Dec 2011 |
The primary objective of the study was to evaluate the persistence of meningococcal antibodies in terms of the percentage of subjects with rabbit serum bactericidal assay (rSBA) titres ≥1:8 for each of the four serogroups (rSBA-MenA, rSBA-MenC, rSBA-MenW-135, rSBA-MenY) at 24, 36, 48 and 60 months after primary vaccination of adolescents with MenACWY-TT or Mencevax™ ACWY vaccine.
To support the data obtained by rSBA testing, antibody concentrations against meningococcal polysaccharides are planned to be assessed by ELISA (anti-polysaccharides [PS] testing) at 24, 36, 48 and 60 months after primary vaccination with MenACWY-TT. The anti-PS testing will be performed at 24 months after vaccine administration, but the sponsor decided not to perform the anti-PS testing at 36, 48 and 60 months after vaccine administration for the following reasons:
•the World Health Organisation (WHO) considers SBA the primary means of assessing immune response to meningococcal conjugate vaccines [WHO, 2006; WHO, 1999].
•circulating bactericidal antibodies are more critical for persistent protection against meningococcal disease than non-functional antibodies against meningococcal polysaccharides [Centres for Disease Control (CDC), 2011; WHO, 2006].
Although antibody concentrations will not be determined by ELISA at 36, 48 and 60 months after primary vaccination with MenACWY-TT or, all subjects will be informed of their rSBA antibody titres at each immunogenicity time point when statistical analyses at that time point have been completed.
In addition:
•The protocol amendment clarifies in which laboratory the different assays will be performed.
•The introduction has been updated with the current licensing status of competitor vaccines and the current recommendations for meningococcal vaccines. The rationale for the study has been updated according to this new information.
•The list of abbreviations and reference list have been updated according to changes in the clinical study team. |
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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 |