Clinical Trial Results:
The Polysaccharide Antibody Response Study: Typhim Vi response and allohemagglutinins versus Pneumo 23 vaccine response in the diagnosis of Specific Polysaccharide Antibody Deficiency.
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Summary
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EudraCT number |
2014-003007-29 |
Trial protocol |
BE |
Global end of trial date |
20 Aug 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Jul 2024
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First version publication date |
28 Jul 2024
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Other versions |
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Summary report(s) |
SPAD definition summary SPAD in patients |
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 |
2014-0087054
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
KU Leuven
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Sponsor organisation address |
Krakenstraat, Leuven, Belgium, 3000
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Public contact |
Clinical Trial Center, KU Leuven - University Hospitals Leuven, 32 1634 19 98, ctc@uzleuven.be
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Scientific contact |
Clinical Trial Center, KU Leuven - University Hospitals Leuven, 32 1634 19 98, ctc@uzleuven.be
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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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Aug 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Aug 2018
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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 |
The purpose of this study is to assess the diagnostic value of the Typhim antibody response and allohemagglutinin titers as an alternative to the Pneumovax 23 response to detect polysaccharide specific antibody deficiency.
Primary objective:
• To establish whether antibody response to Typhim in patients with suspected PID (1) and in healthy adults (2) is non-inferior relative to the antibody response to Pneumovax 23.
• To assess the correlation between Typhim antibody response and the pneumococcal antibody response.
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Protection of trial subjects |
The protocol was evaluated and approved by the Ethics Committee of the University Hospitals Leuven. The study was carried out in accordance with protocol regulations and written informed consent was obtained from all subjects / their parents or legal guardians, in accordance with the Declaration of Helsinki.
The included patients were treated in routine clinical care.
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
02 Mar 2015
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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 |
Belgium: 199
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Worldwide total number of subjects |
199
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EEA total number of subjects |
199
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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) |
70
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Adolescents (12-17 years) |
19
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Adults (18-64 years) |
110
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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 |
Healthy volunteers will be recruited through posters ad valvas in the KU Leuven buildings and through advertisement on UZ Leuven intranet . In addition, persons presenting at the travel consultation will be recruited. Patients necessitating humoral immunodeficiency will be recruited. | ||||||||||||
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Pre-assignment
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Screening details |
Healthy volunteers: 100 screened and recruited. Patients: 99 were recruited. Five did not conclude study: 3 did not receive Thypimvi vaccine, to withdrew as they wished to no longer participate. | ||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
199 | ||||||||||||
Number of subjects completed |
199 | ||||||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Vaccination | ||||||||||||
Arm description |
All patients and HC received Pneumovax and Tymphimvi. Blood sample (serum) is obtained prior to and 4 w after vaccination. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Pneumovax
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled syringe
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Pneumovax and Typhimvi were adminstered IM at two distinc sites right and left deltoid muscle (unless contraindication for IM administration)
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Investigational medicinal product name |
Typhim Vi
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Intramuscular use
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Dosage and administration details |
all subjects to receive IM Pneumovax and Typhim vi at two distinct sites, deltoid R and L, unless contraindication
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Subjects for analysis
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Subject analysis set type |
Per protocol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Healthy volunteers and patients evaluated for humoral immunodeficiency received the UPV vaccine and polysacharide typhim vi vaccine and were analysed by blood sample prior to and 4 weeks after vaccination.
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End points reporting groups
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Reporting group title |
Vaccination
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Reporting group description |
All patients and HC received Pneumovax and Tymphimvi. Blood sample (serum) is obtained prior to and 4 w after vaccination. | ||
Subject analysis set title |
Subjects for analysis
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Healthy volunteers and patients evaluated for humoral immunodeficiency received the UPV vaccine and polysacharide typhim vi vaccine and were analysed by blood sample prior to and 4 weeks after vaccination.
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End point title |
polysaccharide vaccine response - primary endpoint [1] | ||||||||||||
End point description |
1. Pearson correlations between the pneumococcal antibody response and Typhim Vi antibody response.
• Time: at inclusion of minimum 82 subjects per cohort and at trial end
• Level of clinical significance: correlation index greater than 0.65 with p < 0.05
• Data set: all subjects, two cohorts separately
2. Sensitivity, specificity, PPV, NPV and likelihood ratios of Typhim Vi response and AHA with Pneumovax 23 response used as a reference standard to define polysaccharide antibody deficient subjects.
• Time: at inclusion of 82 subjects per cohort and at trial end
• Data set: all subjects, two cohorts separately
3. Multiple logistic regression analysis will be used to study association of low test results with clinical characteristics of pneumococcal antibody deficiency.
• Time: at inclusion of 82 subjects per cohort and at trial end
• Level of significance: Odd’s ratio ≠ 1 with p <0.05
• Data set: all subjects, two cohorts separately
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End point type |
Primary
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End point timeframe |
Response measured 4 weeks after vaccination.
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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: This study is in fact a single arm study design in which we measure the response to two vaccines in order to establish "normal values" and in order to test the correlation between the responses to the two vaccines in the same individuals. As such, this is a single arm trial and there is no comparison group. |
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Attachments |
Healthy subjects responses patient responses Statistics |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
correlation UPV and typhim vi | |||||||||
End point description |
correlation y.n
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End point type |
Primary
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End point timeframe |
after visit 2
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| Notes [2] - withdrawal of consent 2 - protocol deviation 3 [3] - 5 patients excluded based on withdrawal (2) or protocol deviation( 3) |
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Statistical analysis title |
Analysis of correlation | |||||||||
Statistical analysis description |
correlation between response to upv and typhimvi
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Comparison groups |
Vaccination v Subjects for analysis
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Number of subjects included in analysis |
393
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Analysis specification |
Pre-specified
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Analysis type |
other [4] | |||||||||
P-value |
< 0.05 | |||||||||
Method |
1. Pearson correlations between the pneu | |||||||||
Confidence interval |
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| Notes [4] - Pearson Correlation |
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Adverse events information
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Timeframe for reporting adverse events |
All subjects questioned and physically examined for AE to the vaccine on both study visits (pre-vaccintion sample, and vaccination at visit 1 - post- vaccination sample at visit 2).
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Adverse event reporting additional description |
Adverse events will be recorded in the Case Report Form at first visit (immediate adverse events) and at the second visit (adverse events between the first and the second visit). In case of any adverse event the principal investigator has to be notified.
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Assessment type |
Systematic | ||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
SNOMED CT | ||||||||||||||||
Dictionary version |
CT
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Reporting groups
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Reporting group title |
Evaluation group
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Reporting group description |
HC and patients receiving both vaccines and samples available for evaluation. | ||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/31705452 http://www.ncbi.nlm.nih.gov/pubmed/28553290 |
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