Clinical Trial Results:
A phase III, randomized, open, controlled, multicenter primary vaccination study to demonstrate the non inferiority of the immunogenicity of GSK Biologicals’ meningococcal serogroup ACWY conjugate vaccine when given as one dose with Twinrix versus GSK Biologicals’ meningococcal serogroup ACWY conjugate vaccine alone and versus Twinrix alone in healthy subjects aged 11 through 17 years
Summary
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EudraCT number |
2006-005999-41 |
Trial protocol |
SE DK |
Global end of trial date |
28 Apr 2008
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Results information
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Results version number |
v2(current) |
This version publication date |
25 May 2018
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First version publication date |
26 Feb 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 |
109063
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00465816 | ||
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,
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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) |
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 |
23 Jan 2009
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
28 Apr 2008
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Apr 2008
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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 |
To demonstrate the non-inferiority of the MenACWY-TT conjugate vaccine co-administered with Twinrix as compared to the MenACWY-TT conjugate vaccine administered alone with respect to the serum bactericidal antibody geometric mean titres as measured using baby rabbit complement (rSBA GMTs) for N. meningitidis serogroups A, C, W-135 and Y.
To demonstrate the non-inferiority of the MenACWY-TT conjugate vaccine co-administered with Twinrix as compared to Twinrix administered alone with respect to the percentage of seroconversion for hepatitis A and percentage of seroprotection for hepatitis B.
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Protection of trial subjects |
All subjects were supervised for 30 min after vaccination with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 Apr 2007
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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 |
Sweden: 337
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Country: Number of subjects enrolled |
Denmark: 274
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Worldwide total number of subjects |
611
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EEA total number of subjects |
611
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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) |
611
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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 was performed: informed consent was obtained and signed from parents or guardians of subjects, check for inclusion/exclusion criteria and contraindications/precautions was performed, and medical history of subjects was collected. | ||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (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 + Twinrix Group | ||||||||||||||||||||
Arm description |
Subjects received 1 dose of Nimenrix vaccine at Month 0 and 1 dose of Twinrix vaccine at Months 0, 1 and 6. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Nimenrix (Meningococcal vaccine 134612)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Single dose intramuscular injection
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Investigational medicinal product name |
Twinrix
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
3-dose intramuscular injection.
Twinrix Adult will be administered to subjects aged 16 years and above and Twinrix Junior will be administered to subjects aged from 11 years up to and including 15 years of age.
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Arm title
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Nimenrix Group | ||||||||||||||||||||
Arm description |
Subjects received 1 dose of Nimenrix vaccine at Month 0. | ||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||
Investigational medicinal product name |
Nimenrix (Meningococcal vaccine 134612)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Single dose intramuscular injection
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Arm title
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Twinrix Group | ||||||||||||||||||||
Arm description |
Subjects received 1 dose of Twinrix vaccine at Months 0, 1 and 6. | ||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||
Investigational medicinal product name |
Twinrix
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
3-dose intramuscular injection.
Twinrix Adult will be administered to subjects aged 16 years and above and Twinrix Junior will be administered to subjects aged from 11 years up to and including 15 years of age.
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Baseline characteristics reporting groups
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Reporting group title |
Nimenrix + Twinrix Group
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Reporting group description |
Subjects received 1 dose of Nimenrix vaccine at Month 0 and 1 dose of Twinrix vaccine at Months 0, 1 and 6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Nimenrix Group
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Reporting group description |
Subjects received 1 dose of Nimenrix vaccine at Month 0. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Twinrix Group
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Reporting group description |
Subjects received 1 dose of Twinrix vaccine at Months 0, 1 and 6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Nimenrix + Twinrix Group
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Reporting group description |
Subjects received 1 dose of Nimenrix vaccine at Month 0 and 1 dose of Twinrix vaccine at Months 0, 1 and 6. | ||
Reporting group title |
Nimenrix Group
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Reporting group description |
Subjects received 1 dose of Nimenrix vaccine at Month 0. | ||
Reporting group title |
Twinrix Group
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Reporting group description |
Subjects received 1 dose of Twinrix vaccine at Months 0, 1 and 6. |
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End point title |
Antibody titers for meningococcal polysaccharide serum bactericidal assay using baby rabbit complement (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) [1] | ||||||||||||||||||||||||
End point description |
The rSBA titers were expressed as geometric mean titers.
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End point type |
Primary
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End point timeframe |
At 1 month after vaccination with Nimenrix vaccine (Month 1)
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Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
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Statistical analysis title |
Non-inferiority in term of rSBA-MenC GMT | ||||||||||||||||||||||||
Statistical analysis description |
To assess the Non-inferiority of the Nimenrix+Twinrix group compared to Nimenrix one, Two-sided 95% CI from ANCOVA model on the GMTs ratio (Nimenrix+Twinrix group over Nimenrix group) was computed. The model was adjusted for age strata and baseline titre.
The lower limit of the two-sided 95% CI on the ratio of rSBA-MenA GMTs between Nimenrix + Twinrix group and (over) Nimenrix group was ≥ 0.5.
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Comparison groups |
Nimenrix + Twinrix Group v Nimenrix Group
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Number of subjects included in analysis |
475
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||||||||
Method |
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Parameter type |
Adjusted GMT ratio | ||||||||||||||||||||||||
Point estimate |
0.91
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.68 | ||||||||||||||||||||||||
upper limit |
1.21 | ||||||||||||||||||||||||
Statistical analysis title |
Non-inferiority in term of rSBA-MenC GMT | ||||||||||||||||||||||||
Statistical analysis description |
To assess the Non-inferiority of the Nimenrix+Twinrix group compared to Nimenrix one, Two-sided 95% CI from ANCOVA model on the GMTs ratio (Nimenrix+Twinrix group over Nimenrix group) was computed. The model was adjusted for age strata and baseline titre.
The lower limit of the two-sided 95% CI on the ratio of rSBA-MenC GMTs between Nimenrix + Twinrix group and (over) Nimenrix group was ≥ 0.5.
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Comparison groups |
Nimenrix + Twinrix Group v Nimenrix Group
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Number of subjects included in analysis |
475
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||||||||
Method |
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Parameter type |
Adjusted GMT ratio | ||||||||||||||||||||||||
Point estimate |
0.91
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.68 | ||||||||||||||||||||||||
upper limit |
1.21 | ||||||||||||||||||||||||
Statistical analysis title |
Non-inferiority in term of rSBA-MenW-135 GMT | ||||||||||||||||||||||||
Statistical analysis description |
To assess the Non-inferiority of the Nimenrix+Twinrix group compared to Nimenrix one, Two-sided 95% CI from ANCOVA model on the GMTs ratio (Nimenrix+Twinrix group over Nimenrix group) was computed. The model was adjusted for age strata and baseline titre.
The lower limit of the two-sided 95% CI on the ratio of rSBA-MenW-135 GMTs between Nimenrix + Twinrix group and (over) Nimenrix group was ≥ 0.5.
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Comparison groups |
Nimenrix Group v Nimenrix + Twinrix Group
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Number of subjects included in analysis |
475
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||||||||
Method |
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Parameter type |
Adjusted GMT ratio | ||||||||||||||||||||||||
Point estimate |
1.02
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.87 | ||||||||||||||||||||||||
upper limit |
1.19 | ||||||||||||||||||||||||
Statistical analysis title |
Non-inferiority in term of rSBA-MenY GMT | ||||||||||||||||||||||||
Statistical analysis description |
To assess the Non-inferiority of the Nimenrix+Twinrix group compared to Nimenrix one, Two-sided 95% CI from ANCOVA model on the GMTs ratio (Nimenrix+Twinrix group over Nimenrix group) was computed. The model was adjusted for age strata and baseline titre.
The lower limit of the two-sided 95% CI on the ratio of rSBA-MenY GMTs between Nimenrix + Twinrix group and (over) Nimenrix group was ≥ 0.5.
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Comparison groups |
Nimenrix + Twinrix Group v Nimenrix Group
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Number of subjects included in analysis |
475
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||||||||
Method |
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Parameter type |
Adjusted GMT ratio | ||||||||||||||||||||||||
Point estimate |
1.01
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.85 | ||||||||||||||||||||||||
upper limit |
1.19 |
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End point title |
Number of subjects seroconverted for hepatitis A [2] | ||||||||||||
End point description |
A seroconverted subject was defined as a subject with anti-Hepatitis A virus (HAV) antibody concentration greater than or equal to 15 milli-International Units per Milliliter (mIU/mL) in previously seronegative subjects.
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End point type |
Primary
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End point timeframe |
At 1 month after the third dose of Twinrix vaccine (Month 7)
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Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
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Statistical analysis title |
Non-inferiority in term of seroconversion rate | ||||||||||||
Comparison groups |
Nimenrix + Twinrix Group v Twinrix Group
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Number of subjects included in analysis |
416
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | ||||||||||||
Method |
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Parameter type |
Percentage difference | ||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.19 | ||||||||||||
upper limit |
3.9 | ||||||||||||
Notes [3] - To assess the Non-inferiority of the Nimenrix+Twinrix group compared to Twinrix one, two-sided standardized asymptotic 95% CI for the difference in seroconversion rates for hepatitis A (Nimenrix+Twinrix group minus Twinrix group) was computed. The lower limit of the two-sided standardised asymptotic 95% CI for group difference (Nimenrix+Twinrix group minus Twinrix group) in the percentage of subjects with vaccine seroconversion was ≥ pre-defined clinical limit of -10%. |
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End point title |
Number of subjects seroprotected for hepatitis B [4] | ||||||||||||
End point description |
A seroprotected subject was defined as a subject with anti-Hepatitis B surface antigen (HBs) antibody concentration greater than or equal to 10 milli-International Units per Milliliter (mIU/mL).
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End point type |
Primary
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End point timeframe |
At 1 month after the third dose of Twinrix vaccine (Month 7)
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Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
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Statistical analysis title |
Non-inferiority in term of seroprotection rate | ||||||||||||
Comparison groups |
Twinrix Group v Nimenrix + Twinrix Group
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Number of subjects included in analysis |
427
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [5] | ||||||||||||
Method |
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Parameter type |
Percentage difference | ||||||||||||
Point estimate |
-0.91
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-2.64 | ||||||||||||
upper limit |
2.92 | ||||||||||||
Notes [5] - To assess the Non-inferiority of the Nimenrix+Twinrix group compared to the Twinrix one, two-sided standardized asymptotic 95% CI for the difference in seroprotection rates for hepatitis B (Nimenrix+Twinrix group minus Twinrix group) was computed. The lower limit of the two-sided standardised asymptotic 95% CI for group difference (Nimenrix+Twinrix group minus Twinrix group) in the percentage of subjects with vaccine seroconversion was ≥ pre-defined clinical limit of -10%. |
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End point title |
Number of subjects with a vaccine response to MenA, MenC, MenY and MenW-135 [6] | |||||||||||||||||||||
End point description |
Vaccine response is defined as an rSBA titer of at least 1:32 in subjects initially seronegative [rSBA titer below1:8] and as a 4-fold increase in titer in subjects initially seropositive [rSBA titre greater than or equal to 1:8].
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End point type |
Secondary
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End point timeframe |
At 1 month after vaccination with Nimenrix vaccine (Month 1)
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Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
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No statistical analyses for this end point |
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End point title |
Number of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titers above predefined cut-off values [7] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The cut-off values assessed were greater than or equal to (≥) 1:8 and ≥ 1:128.
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End point type |
Secondary
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End point timeframe |
Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1)
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Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
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No statistical analyses for this end point |
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End point title |
Anti-PSA (polysaccharide A), anti-PSC (polysaccharide C), anti-PSW-135 (polysaccharide W-135), and anti-PSY (polysaccharide Y) antibody concentrations [8] | ||||||||||||||||||||||||||||||||||||
End point description |
Concentrations were provided as Geometric Mean Concentrations expressed as micrograms per milliliter (µg/mL).
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End point type |
Secondary
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End point timeframe |
Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1)
|
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Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects with Anti-PSA, anti-PSC, anti-PSW-135, and anti-PSY antibody concentrations above pre-defined cut-off values [9] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The cut-off values assessed include greater than or equal to (≥) 0.3 micrograms per milliliter (µg/mL) and ≥ 2.0 µg/mL.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Anti-Tetanus toxoid (TT) antibody concentrations [10] | ||||||||||||||||||
End point description |
Concentrations were provided as Geometric Mean Concentrations expressed as International Units per milliliter (IU/mL).
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1)
|
||||||||||||||||||
Notes [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
|||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of subjects with anti-tetanus toxoid antibody concentrations above the pre-defines cut-off value [11] | |||||||||||||||
End point description |
The cut-off value assessed was greater than or equal to 0.1 International Units per milliliter (IU/mL).
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1)
|
|||||||||||||||
Notes [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
||||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titers at Month 7 [12] | ||||||||||||||||||||||||
End point description |
The rSBA titers were expressed as geometric mean titers.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
At 7 months after vaccination with Nimenrix (At Month 7)
|
||||||||||||||||||||||||
Notes [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Number of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titers above predefined cut-off values at Month 7 [13] | |||||||||||||||||||||||||||||||||
End point description |
The cut-off values assessed were greater than or equal to (≥) 1:8 and ≥ 1:128.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
At 7 months after vaccination with Nimenrix (At Month 7)
|
|||||||||||||||||||||||||||||||||
Notes [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Anti-PSA, anti-PSC, anti-PSW-135 and anti-PSY antibody concentrations at Month 7 [14] | ||||||||||||||||||||||||
End point description |
Concentrations were provided as Geometric Mean Concentrations expressed as micrograms per milliliter (µg/mL).
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
At 7 months after vaccination with Nimenrix (At Month 7)
|
||||||||||||||||||||||||
Notes [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Number of subjects with anti-PSA, anti-PSC, anti-PSW-135 and anti-PSY antibody concentrations above pre-defined cut-off values at Month 7 [15] | |||||||||||||||||||||||||||||||||
End point description |
The cut-off values assessed include greater than or equal to (≥) 0.3 micrograms per milliliter (µg/mL) and ≥ 2.0 µg/mL.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
At 7 months after vaccination with Nimenrix (At Month 7)
|
|||||||||||||||||||||||||||||||||
Notes [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Immunoglobulin G (IgG) anti-HAV antibody concentrations [16] | ||||||||||||||||||
End point description |
Concentrations are given as Geomatric Mean Concentrations expressed as milli-Internatinal Units per Milliliter (mIU/mL).
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Prior to the first dose (Month 0) and 1 month after the third dose of Twinrix vaccine (Month 7)
|
||||||||||||||||||
Notes [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
|||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of subjects with IgG anti-HAV antibody concentrations above the pre-defined cut-off value [17] | |||||||||||||||
End point description |
The cut-off value assessed was greater than or equal to 15 milli-Internatinal Units per Milliliter (mIU/mL).
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Prior to the first dose (Month 0) and 1 month after the third dose of Twinrix vaccine (Month 7)
|
|||||||||||||||
Notes [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
||||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
IgG anti-HBs antibody concentrations [18] | ||||||||||||||||||
End point description |
Concentrations are given as Geomatric Mean Concentrations expressed as milli-Internatinal Units per Milliliter (mIU/mL).
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Prior to the first dose (Month 0) and 1 month after the third dose of Twinrix vaccine (Month 7)
|
||||||||||||||||||
Notes [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
|||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of subjects with IgG anti-HB antibody concentrations above the pre-defined cut-off value [19] | |||||||||||||||
End point description |
The cut-off value assessed was greater than or equal to 10 milli-Internatinal Units per Milliliter (mIU/mL).
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Prior to the first dose (Month 0) and 1 month after the third dose of Twinrix vaccine (Month 7)
|
|||||||||||||||
Notes [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
||||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Number of subjects reporting any solicited local symptoms post-meningococcal vaccination [20] | ||||||||||||||||||
End point description |
Solicited local symptoms assessed include pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
During a 4-day period (Days 0-3) after Nimenrix vaccination
|
||||||||||||||||||
Notes [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
|||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects reporting any solicited local symptoms post-Twinrix vaccination [21] | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited local symptoms assessed include pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.
|
|||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
During a 4-day period (Days 0-3) after each Twinrix vaccination, and across doses
|
|||||||||||||||||||||||||||||||||||||||||||||
Notes [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||
End point title |
Number of subjects reporting any solicited general symptoms | ||||||||||||||||||||||||||||
End point description |
Solicited general symptoms assessed include fatigue, fever (axillary temperature greater than or equal to 37.5 degrees Celcius), gastrointestinal symptoms and headache. Any = occurrence of the symptom regardless of intensity grade. Dose 1 = post-Nimenrix and post-Twinrix for the Nimenrix + Twinrix Group, post-Twinrix for the Twinrix Group and post-Nimenrix for the Nimenrix Group.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
During a 4-day period (Days 0-3) after first vaccine dose (Dose 1)
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Number of subjects reporting any unsolicited adverse events (AEs) | ||||||||||||||||
End point description |
Unsolicited AE covers any AE 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.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to 1 month post Dose 1 period
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Number of subjects reporting any specific AEs of new onset of chronic illnesses | ||||||||||||||||
End point description |
Specific AEs of new onset of chronic illnesses include e.g. autoimmune disorders, asthma, type I diabetes and allergies.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
During the entire study (up to Month 7)
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Number of subjects reporting any rash | ||||||||||||||||
End point description |
Rashes include e.g. hives, idiopathic thrombocytopenic purpura, petechiae.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
During the entire study (up to Month 7)
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Number of subjects reporting any conditions prompting emergency room visits | ||||||||||||||||
End point description |
|||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
During the entire study (up to Month 7)
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
During the entire study (up to Month 7)
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects reporting any solicited general symptoms [22] | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited general symptoms assessed include fatigue, fever (axillary temperature greater than or equal to 37.5 degrees Celcius), gastrointestinal symptoms and headache. Any = occurrence of the symptom regardless of intensity grade. Dose 2 (D2), 3 (D3)and Across doses (AD)= post-Twinrix for the Nimenrix + Twinrix Group and for the Twinrix Group.
|
|||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
During a 4-day period (Days 0-3) after second (Dose 2), third (Dose 3) Twinrix vaccine dose and across doses
|
|||||||||||||||||||||||||||||||||||||||||||||
Notes [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of subjects reporting any unsolicited adverse events (AEs) [23] | |||||||||||||||
End point description |
Unsolicited AE covers any AE 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.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Up to 1 month post Dose 2 (D2) and post Dose 3 (D3) Twinrix vaccine
|
|||||||||||||||
Notes [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The results in this study were tabulated by the type of vaccine administered. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, who received the vaccine mentioned in the time frame, while the results for multiple endpoints account for all baseline groups. |
||||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Serious Adverse Events were reported throughout the entire study period (up to Month 7). Unsolicited Adverse Events (AE) were reported up to one month after each vaccine dose.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Other Frequent (non-serious) Adverse Events were reported during a 4-day follow-up period only for those subjects who received the vaccination and completed their symptom sheet.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Nimenrix + Twinrix Group
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received 1 dose of Nimenrix vaccine at Month 0 and 1 dose of Twinrix vaccine at Months 0, 1 and 6. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Nimenrix Group
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received 1 dose of Nimenrix vaccine at Month 0. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Twinrix Group
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received 1 dose of Twinrix vaccine at Months 0, 1 and 6. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: This solicited local symptom was only collected from 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: This solicited local symptom was only collected from 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: This solicited local symptom was only collected from 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: This solicited general symptom was only collected from 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: This solicited general symptom was only collected from 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: This solicited general symptom was only collected from 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 |