Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Phase III, randomized, double-blind, multicentre clinical trial on clinical efficacy and safety of platelet concentrates treated with the THERAFLEX UV-Platelets procedure in comparison to conventional platelet components (Capture).

    Summary
    EudraCT number
    		 2015-001035-20
    Trial protocol
    		 DE  
    Global end of trial date
    11 Mar 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 Aug 2021
    First version publication date
    20 Aug 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    PIPL002a
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    DRK Blood Service NSTOB
    Sponsor organisation address
    Eldagsener Strasse 38, Springe, Germany, 31832
    Public contact
    R&D Department, Clinical Trial Group, DRK-Blood Service NSTOB, +49 5041 772 310, SekretariatFuE@bsd-nstob.de
    Scientific contact
    R&D Department, Clinical Trial Group, DRK-Blood Service NSTOB, +49 5041 772 310, SekretariatFuE@bsd-nstob.de
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Jun 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 Mar 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Mar 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the trial was to demonstrate the non-inferiority of UVC-treated plasma reduced platelet concentrates (synonym: UVC-PLT in comparison to standard untreated plasma reduced platelet concentrates (synonym: Control PLT) stored for up to 5 days in adult patients with hematologic or oncologic diseases and thrombocytopenia. The non-inferiority was met if the mean 1-hour Corrected Count Increment (1-hour CCI) between the control and UVC-PLT group was not more than 30% below the control.
    Protection of trial subjects
    The trial was conducted according to ICH-GCP guidelines, the applicable local laws and regulations, and in accordance with the ethical principles that have their origins in the Declaration of Helsinki. Regulatory authorities were notified of the trial as required by national regulations, and where necessary relevant authorization was obtained. An IDMC was involved in order to monitore safety data at regular intervals, making recommendations related to safety relevant issues (i.e. continuing/stopping the trial). In particular, the IDMC assessed and approved the safety data during the stepwise enrolment of patients in terms of increasing risk for the development of TA-GvHD at the beginning of the study. In step 1 only patients not at risk for the development of transfusion associated graft versus host disease (TA-GvHD) were enrolled, in step 2 patients at risk for TA-GvHD exluding patients with allogeneic stem cell transplantation, and in step 3 also patients with allogeneic stem cell transplantation were enrolled into the study.
    Background therapy
    		 There were no prohibited concomitant therapies. The patients received concomitant therapy following medical instructions.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Oct 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 175
    Worldwide total number of subjects
    175
    EEA total number of subjects
    175
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    127
    From 65 to 84 years
    48
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 175 patients were randomized at 10 sites in Germany.

    Pre-assignment
    Screening details
    		 177 patients were screened, whereas 175 patients were enrolled. Two patients in each arm were excluded because no PLT transfusion was performed within the specified time period of 6 weeks after randomisation. Hence, a total of 171 patients received as minimum one PLT Transfusion (n=87 in the UVC-PLT arm and n=84 in the Control-PLT arm).

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst
    Blinding implementation details
    The only health care professionals that knew the treatment that a patient received were the transfusion medicine staff from the manufacturing sites. The IDMC was unblinded when medically indicated.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 UVC-PLT
    Arm description
    		 Patients received pathogen-reduced platelet concentrates prepared by apheresis or buffy coat procedure (UVC-PLT) stored for up to 5 days before transfusion. Pathogen reduction was performed by UVC-irradiation using the THERAFLEX UV-Platelets procedure. UVC-PLTs were not gamma-irradiated because UVC treament is sufficient to prevent TA-GvHD. The treatment period started on the day of the first study PLT transfusion and continued for a maximum of 8 PLT transfusion episode within 28 days. Baseline characteristics were evaluated for all patients who received at least one UVC-PLT transfusion (ITT-set, n=87). A complete safety follow-up period of 30 days was performed in 71 patients.
    Arm type
    		 Experimental

    Investigational medicinal product name
    THERAFLEX UV-Platelets
    Investigational medicinal product code
    Other name
    Pathogen-reduced, plasma-reduced platelet concentrates stored in SSP+additive solution
    Pharmaceutical forms
    Concentrate and solvent for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    After randomisation patients received prophylactic or therapeutic PLT transfusions in accordance to the German cross section guideline for therapy with blood components. Typically, one or more platelet units were transfused when the PLT count was 10E9/L or lower. However, the dose and frequency of administration also depended on the individual decision by the attending physician. In this clinical trial a mean of 3.7 PLT units (about 350 ml, 3.5 x 10E11 PLTs, each) were transfused during the treatment period of 28 days. UVC-PLTs were not gamma-irradiated, because UVC-treatment is sufficient to prevent TA-GvHD.

    Arm title
    		 Control-PLT
    Arm description
    		 Patients received standard plasma-reduced platelet concentrates prepared by apheresis or buffy coat procedure (Control-PLT) stored for up to 5 days before transfusion. In contrast to UVC-PLTs, Control-PLTs were gamma-irradiated for TA-GvHD prophylaxis, when medically indicated. The treatment period started on the day of the first study PLT transfusion and continued for a maximum of 8 platelet transfusion episodes within 28 days. Baseline characteristics were evaluated for all patients who received at least one Control-PLT transfusion (ITT-set, n=84 patients). A complete safety follow-up period of 30 days was performed in 69 patients.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Untreated plasma reduced platelet concentrates stored in SSP+ additive solution
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    After randomisation patients received prophylactic or therapeutic PLT transfusions in accordance to the German cross section guideline for therapy with blood components. Typically, one or more platelet units were transfused when the PLT count was 10E9/L or lower. However, the dose and frequency of administration also depended an the individual decision by the attending physician. In this clinical trial a mean of 3.0 PLT units (about 350 ml, 3.5 x 10E11 PLT, each) were transfused during the treatment period of 28 days.

    Number of subjects in period 1 [1]
    		UVC-PLT Control-PLT
    Started
    87
    84
    Completed
    71
    69
    Not completed
    16
    15
         Adverse event, serious fatal
    2
    1
         Consent withdrawn by subject
    2
    -
         Exclusion criteria were met
    -
    2
         other reasons
    -
    1
         Transfusion of routine PLT units or from other arm
    12
    11
    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: 177 patients were screened, whereas 175 patients were enrolled. Two patients in each arm were excluded because no PLT transfusion was performed within the specified time period of 6 weeks after randomisation. Hence, a total of 171 patients received as minimum one PLT Transfusion (n=87 in the UVC-PLT arm and n=84 in the Controi-PLT arm).

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    UVC-PLT
    Reporting group description
    		 Patients received pathogen-reduced platelet concentrates prepared by apheresis or buffy coat procedure (UVC-PLT) stored for up to 5 days before transfusion. Pathogen reduction was performed by UVC-irradiation using the THERAFLEX UV-Platelets procedure. UVC-PLTs were not gamma-irradiated because UVC treament is sufficient to prevent TA-GvHD. The treatment period started on the day of the first study PLT transfusion and continued for a maximum of 8 PLT transfusion episode within 28 days. Baseline characteristics were evaluated for all patients who received at least one UVC-PLT transfusion (ITT-set, n=87). A complete safety follow-up period of 30 days was performed in 71 patients.

    Reporting group title
    Control-PLT
    Reporting group description
    		 Patients received standard plasma-reduced platelet concentrates prepared by apheresis or buffy coat procedure (Control-PLT) stored for up to 5 days before transfusion. In contrast to UVC-PLTs, Control-PLTs were gamma-irradiated for TA-GvHD prophylaxis, when medically indicated. The treatment period started on the day of the first study PLT transfusion and continued for a maximum of 8 platelet transfusion episodes within 28 days. Baseline characteristics were evaluated for all patients who received at least one Control-PLT transfusion (ITT-set, n=84 patients). A complete safety follow-up period of 30 days was performed in 69 patients.

    Reporting group values
    		 UVC-PLT Control-PLT Total
    Number of subjects
    		 87 84 171
    Age categorical
    Units: Subjects
        Adults (18 to 80 years)
    		 87 84 171
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 57 ± 14 55 ± 12 -
    Gender categorical
    Units: Subjects
        Female
    		 32 32 64
        Male
    		 55 52 107
    Primary diagnosis
    Units: Subjects
        Acute lymphoblastic leukemia
    		 7 2 9
        Acute myeloid leukemia
    		 40 30 70
        Chronic leukemia
    		 1 0 1
        Multiple myeloma
    		 22 26 48
        Non-Hodgkin's Iymphoma
    		 9 16 25
        Hodgkin's Iymphoma
    		 0 3 3
        Other
    		 8 7 15
    Body Surface area
    Units: qm
        arithmetic mean (standard deviation)
    		 1.95 ± 0.20 1.97 ± 0.23 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    UVC-PLT
    Reporting group description
    		 Patients received pathogen-reduced platelet concentrates prepared by apheresis or buffy coat procedure (UVC-PLT) stored for up to 5 days before transfusion. Pathogen reduction was performed by UVC-irradiation using the THERAFLEX UV-Platelets procedure. UVC-PLTs were not gamma-irradiated because UVC treament is sufficient to prevent TA-GvHD. The treatment period started on the day of the first study PLT transfusion and continued for a maximum of 8 PLT transfusion episode within 28 days. Baseline characteristics were evaluated for all patients who received at least one UVC-PLT transfusion (ITT-set, n=87). A complete safety follow-up period of 30 days was performed in 71 patients.

    Reporting group title
    Control-PLT
    Reporting group description
    		 Patients received standard plasma-reduced platelet concentrates prepared by apheresis or buffy coat procedure (Control-PLT) stored for up to 5 days before transfusion. In contrast to UVC-PLTs, Control-PLTs were gamma-irradiated for TA-GvHD prophylaxis, when medically indicated. The treatment period started on the day of the first study PLT transfusion and continued for a maximum of 8 platelet transfusion episodes within 28 days. Baseline characteristics were evaluated for all patients who received at least one Control-PLT transfusion (ITT-set, n=84 patients). A complete safety follow-up period of 30 days was performed in 69 patients.

    Primary: Camparison of the mean 1-hour CCI between patients transfused with UVC-PLTs and patients transfused with Control-PLTs

    		 Close Top of page
    End point title
    		 Camparison of the mean 1-hour CCI between patients transfused with UVC-PLTs and patients transfused with Control-PLTs
    End point description
    The primary endpoint of PLT therapeutic efficacy was assessed by calculating the post-transfusion 1- hour CCI for the first 8 PLT transfusion episodes. The CCI measures the count increase (CI) of the PLTs after PLT transfusion, corrected for the patients blood volume and number of platelets transfused. Platelet counts were measured max. 24-hours before and 1-hour (10 to 90 min.) after PLT transfusion. The ITT set included 87 patients in the UVC-PLT arm and 84 in the Control-PLT arm. A total of 568 PLT units were transfused (320 in the UVC-PLT arm and, 248 in the Control-PLT arm). Descriptive statistics (mean, 95% Cl of the mean, standard deviation, median, 25% and 75% quartiles, minimum and maximum) were performed. Non-inferiority was concluded if the lower Iimit of the 95% CI calculated on the mean CCI of the UVC­ PCs group was not below the lower Iimit of the zone of non-inferiority (up to a 30% reduction in CCI was considered as not inferior).
    End point type
    Primary
    End point timeframe
    1-hour CCI (time range: 10 to 90 min.) after each PLT transfusion measured for up to the first 8 PLT transfusion episodes within the treatment period of 28 days.
    End point values
    		 UVC-PLT Control-PLT
    Number of subjects analysed
    87
    84
    Units: 1-hour CCI
        arithmetic mean (confidence interval 95%)
    12.70 (11.42 to 13.97)
    15.53 (14.18 to 16.88)
    Statistical analysis title
    		 1-hour CCI non-inferiority analysis
    Statistical analysis description
    For analysis the 1-hour CCI, each patient's mean was calculated separately first since the collected data from several measurements can be expected to be linked to the respective individual. Non- inferiority was concluded if the lower limit of the 95% CI calculated on the mean CCI of the UVC-PCs group was not below the lower Iimit of the zone of non-inferiority (up to a 30% reduction in CCI was considered as not inferior).
    Comparison groups
    UVC-PLT v Control-PLT
    Number of subjects included in analysis
    171
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Diff. Mean-Control vs. lower CI UVC (%)
    Point estimate
    12.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.4
         upper limit
    		 14
    Variability estimate
    Standard deviation

    Secondary: Comparison of the mean 24-hour CCI between patients transfused with UVC-PLTs and patients transfused with Control­-PLTs.

    		 Close Top of page
    End point title
    		 Comparison of the mean 24-hour CCI between patients transfused with UVC-PLTs and patients transfused with Control­-PLTs.
    End point description
    For 24-hours CCI evaluation platelet counts were measured 24-hours after PLT transfusion. Descriptive statistics were performed (mean, 95% Cl of the mean, standard deviation, median, 25% and 75% quartiles, minimum and maximum). In this report the mean and standard deviaton are shown.
    End point type
    Secondary
    End point timeframe
    24-hours (18 to 30 hours) were evaluated after each PLT transfusion up to the first 8 PLT transfusion episodes within the treatment period of 28 days.
    End point values
    		 UVC-PLT Control-PLT
    Number of subjects analysed
    87
    84
    Units: 24-hours CCI
        arithmetic mean (standard deviation)
    8.77 ± 5.52
    10.85 ± 6.16
    No statistical analyses for this end point

    Secondary: Comparison of the mean 1-hour Count Increment (CI) between patients transfused with UVC-PLTs and patients transfused with Control-PLTs.

    		 Close Top of page
    End point title
    		 Comparison of the mean 1-hour Count Increment (CI) between patients transfused with UVC-PLTs and patients transfused with Control-PLTs.
    End point description
    Like the CCI, the Count Increment (CI) measures the response to platelet transfusion but do not "correct" for the patient's blood volume and the number of platelets transfused. For CI-evaluation platelet counts were measured max. 24h before and 1-hour (10 to 90 min.) after PLT transfusion. Descriptive statistics (mean, 95% Cl of the mean, standard deviation, median, 25% and 75% quartiles, minimum and maximum) was performed. In this report the mean and standard deviation are shown.
    End point type
    Secondary
    End point timeframe
    1-hour CI (30 to 90 min.) after each PLT transfusion up to the first 8 PLT transfusion episods within the treatment period of 28 days.
    End point values
    		 UVC-PLT Control-PLT
    Number of subjects analysed
    87
    84
    Units: 24-hour CCI
        arithmetic mean (standard deviation)
    22.05 ± 11.35
    27.06 ± 12.25
    No statistical analyses for this end point

    Secondary: Comparison of the mean 24-hour CI between patients transfused with UVC-PLTs and patients transfused with Control-PLTs

    		 Close Top of page
    End point title
    		 Comparison of the mean 24-hour CI between patients transfused with UVC-PLTs and patients transfused with Control-PLTs
    End point description
    Continuous data were summarized using the number of observations, mean, 95% Cl of the mean, standard deviation, median, 25% and 75% quartiles, minimum and maximum. In this report the mean and standard deviation are shown.
    End point type
    Secondary
    End point timeframe
    24-hours CI (18 to 30 hours) were evaluated after each PLT transfusion up to the first 8 PLT transfusion episodes within the treatment period of 28 days.
    End point values
    		 UVC-PLT Control-PLT
    Number of subjects analysed
    87
    84
    Units: 24-hour CI
        arithmetic mean (standard deviation)
    15.07 ± 9.65
    18.94 ± 11.69
    No statistical analyses for this end point

    Secondary: Comparison of the mean number of PLT transfusions between patients transfused with UVC-PLTs and patients transfused with Control-PLTs

    		 Close Top of page
    End point title
    		 Comparison of the mean number of PLT transfusions between patients transfused with UVC-PLTs and patients transfused with Control-PLTs
    End point description
    Comparison of the number of PLT transfusions required in both study arms for the treatment of patient´s thrombocytopenia provides evidence of the efficacy of the tested platelets. Descriptive statistics were performed (number of observations, mean, 95% Cl of the mean, standard deviation, median, 25% and 75% quartiles, minimum and maximum). In this report the mean and standard deviation are shown. Comparisons of both arms were performed using Student's t-test.
    End point type
    Secondary
    End point timeframe
    First PLT transfusion up to the first 8 PLT transfusion episodes within the treatment period of 28 days.
    End point values
    		 UVC-PLT Control-PLT
    Number of subjects analysed
    87
    84
    Units: Numbers
        arithmetic mean (standard deviation)
    3.68 ± 2.38
    2.95 ± 2.22
    Statistical analysis title
    		 p-Value
    Comparison groups
    UVC-PLT v Control-PLT
    Number of subjects included in analysis
    171
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.041
    Method
    		 t-test, 2-sided
    Confidence interval

    Secondary: Comparison of the mean interval between PLT transfusions in patients transfused with UVC-PLTs and patients transfused with Control-PLTs

    		 Close Top of page
    End point title
    		 Comparison of the mean interval between PLT transfusions in patients transfused with UVC-PLTs and patients transfused with Control-PLTs
    End point description
    Comparison of the number of PLT transfusions required in both study arms for the treatment of patient´s thrombocytopenia provides evidence of the efficacy of the tested platelets. Descriptive statistics were performed (number of observations, mean, 95% Cl of the mean, standard deviation, median, 25% and 75% quartiles, minimum and maximum). In this report the mean and standard deviation are shown. Comparisons of both arms were performed using Student's t-test.
    End point type
    Secondary
    End point timeframe
    First PLT transfusion up to the first 8 PLT transfusion episodes within the treatment period of 28 days.
    End point values
    		 UVC-PLT Control-PLT
    Number of subjects analysed
    87
    84
    Units: days
        arithmetic mean (confidence interval 95%)
    2.62 (2.20 to 3.04)
    2.80 (2.26 to 3.34)
    Statistical analysis title
    		 p-Value
    Comparison groups
    UVC-PLT v Control-PLT
    Number of subjects included in analysis
    171
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.59
    Method
    		 t-test, 2-sided
    Confidence interval

    Secondary: Comparison of the number of Red Blood Cell (RBC) transfusions in patients transfused with UVC-PLTs and patients transfused with Control-PLTs.

    		 Close Top of page
    End point title
    		 Comparison of the number of Red Blood Cell (RBC) transfusions in patients transfused with UVC-PLTs and patients transfused with Control-PLTs.
    End point description
    Comparison of the number of Red Blood Cells (RBC) transfusion support in both study arms provides evidence for the efficacy of UVC-PLTs. Descriptive statistics were performed (number of observations, mean, 95% Cl of the mean, standard deviation, median, 25% and 75% quartiles, minimum and maximum). In this report, the mean and standard deviation are shown. Comparisons of both arms were performed using Student's t-test.
    End point type
    Secondary
    End point timeframe
    First PLT transfusion up to the first 8 PLT transfusion episodes within the treatment period of 28 days.
    End point values
    		 UVC-PLT Control-PLT
    Number of subjects analysed
    87
    84
    Units: Number per patient
        arithmetic mean (standard deviation)
    2.71 ± 2.39
    2.20 ± 2.37
    Statistical analysis title
    		 p-Value
    Comparison groups
    UVC-PLT v Control-PLT
    Number of subjects included in analysis
    171
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.16
    Method
    		 t-test, 2-sided
    Confidence interval

    Secondary: Comparison of the rate of clinical refractoriness in patients transfused with UVC-PLTs and patients transfused with Control-PLTs

    		 Close Top of page
    End point title
    		 Comparison of the rate of clinical refractoriness in patients transfused with UVC-PLTs and patients transfused with Control-PLTs
    End point description
    The number of patients with clinical refractoriness to PLT transfusions in the UVC-arm vs. the number of patients with clinical refractoriness to PLT transfusions in the Control-PLT arm were determined. Comparison between both arms was performed using the Fisher's exact test. Episodes of "clinical" refractoriness, defined as two consecutive transfusions, each with a 1-hour CCI lower than 7.5.
    End point type
    Secondary
    End point timeframe
    First PLT transfusion up to the first 8 PLT transfusion episodes within the treatment period of 28 days.
    End point values
    		 UVC-PLT Control-PLT
    Number of subjects analysed
    87
    84
    Units: Number
    15
    6
    Statistical analysis title
    		 p-Value
    Comparison groups
    UVC-PLT v Control-PLT
    Number of subjects included in analysis
    171
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.055
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Comparison of the rate of immunologic refractoriness in patients transfused with UVC-PLTs and patients transfused with Control-PLTs

    		 Close Top of page
    End point title
    		 Comparison of the rate of immunologic refractoriness in patients transfused with UVC-PLTs and patients transfused with Control-PLTs
    End point description
    Number of patients with immunologic refractoriness to PLT transfusions in the UVC-PLT arm vs. Control-PLT arm. Comparison between both arms were performed using Fisher's exact test. Immunologic refractoriness defined as two consecutive transfusions with a CCI lower then 7.5 and serologic conversion to positive tests for HLA and/or allo antibodies or for antibodies to UVC related neoantigens.
    End point type
    Secondary
    End point timeframe
    First PLT transfusion up to the first 8 PLT transfusion episodes within the treatment period of 28 days.
    End point values
    		 UVC-PLT Control-PLT
    Number of subjects analysed
    87 [1]
    84 [2]
    Units: Numbers
    0
    0
    Notes
    [1] - No immunologic refractoriness due to serologic conversion was reported.
    [2] - No immunologic refractoriness due to serologic conversion was reported.
    No statistical analyses for this end point

    Secondary: Comparison of the number of WHO Grad 3 and 4 bleeding in patients transfused with UVC-PLTs and patients transfused with Control-PLTs

    		 Close Top of page
    End point title
    		 Comparison of the number of WHO Grad 3 and 4 bleeding in patients transfused with UVC-PLTs and patients transfused with Control-PLTs
    End point description
    The grade of bleeding was determined using the WHO bleeding scale. The number of cases with severe grade 3 and 4 bleeding were recorded for all patients of the ITT set during the treatment period. Comparison between both arms was performed using either the Chi-Square test or the Fisher's exact test, depending on the data distribution.
    End point type
    Secondary
    End point timeframe
    First PLT transfusion until the end of follow up period.
    End point values
    		 UVC-PLT Control-PLT
    Number of subjects analysed
    87 [3]
    84
    Units: Number
    0
    1
    Notes
    [3] - No grade 3 or 4 bleeding was recorded.
    No statistical analyses for this end point

    Secondary: Comparison of alloimmunisation to UVC-related neoantigens on PLTs

    		 Close Top of page
    End point title
    		 Comparison of alloimmunisation to UVC-related neoantigens on PLTs
    End point description
    The number of patients with alloimmunisation to possible UVC-related neoantigens on PLTs alter transfusion of UVC- PLTs and Control-PLTs, were analyzed. For the evaluation of alloimmunisation blood samples for alloantibody screening were taken before the First PLT transfusion and at the end of the safety follow-up period. Additional samples were taken in case of suspected refractoriness to platelet transfusions. Comparison between both arms was performed using either the Chi-Squaretest or the Fisher's exact test.
    End point type
    Secondary
    End point timeframe
    Overall study period.
    End point values
    		 UVC-PLT Control-PLT
    Number of subjects analysed
    87 [4]
    84 [5]
    Units: Numbers
    0
    0
    Notes
    [4] - No alloimmunisation to UVC-related neoantigens was recorded.
    [5] - No alloimmunisation to UVC-related neoantigenswas recorded
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    First PLT transfusion until 30 days after the last dose of study drug.
    Adverse event reporting additional description
    All safety analysiswas based on ITT population who received at least one PLT transfusion.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    UVC-PLT
    Reporting group description
    		 Patients received UVC-irradiated, plasma reduced, platelet concentrates stored in SSP+ additive solution, manufactured with the THERAFLEX UV-Platelets procedure (UVC-PLTs).

    Reporting group title
    Control-PLT
    Reporting group description
    		 Patients received untreated plasma reduced platelet concentrates stored in SSP+ additive solution. Control-PLTs were gamma-irradiated for TA-GvHD prophylaxis, when medically indicated.

    Serious adverse events
    		 UVC-PLT Control-PLT
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 87 (11.49%)
    8 / 84 (9.52%)
         number of deaths (all causes)
    1
    3
         number of deaths resulting from adverse events
    1
    3
    Investigations
    Sepsis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasma benign, malignant and unspecified,other, Progression of lymphoma
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Paroxysmal atrial tachycardia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 87 (0.00%)
    2 / 84 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fever
         subjects affected / exposed
    1 / 87 (1.15%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    soft tissue infectioncervical with dysphagia
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Immune system disorders-Other GVHD after allogeneic stem cell transplantation; Diarrhea
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Infections and Infestations-other, CMV-infection
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    resp.failure/pneumonia/lung infection (RSV)
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sepsis with organ involvement (CNC, kidney liver) V.a meninigitis, encephalitis
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Catheter related infection
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial infection
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestatations-other, Influenca A infection
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 UVC-PLT Control-PLT
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    85 / 87 (97.70%)
    80 / 84 (95.24%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    8 / 87 (9.20%)
    2 / 84 (2.38%)
         occurrences all number
    9
    2
    Hypertension
         subjects affected / exposed
    9 / 87 (10.34%)
    4 / 84 (4.76%)
         occurrences all number
    12
    6
    Hypotension
         subjects affected / exposed
    2 / 87 (2.30%)
    5 / 84 (5.95%)
         occurrences all number
    2
    5
    General disorders and administration site conditions
    Chilis
         subjects affected / exposed
    4 / 87 (4.60%)
    5 / 84 (5.95%)
         occurrences all number
    6
    5
    Face oedema
         subjects affected / exposed
    3 / 87 (3.45%)
    1 / 84 (1.19%)
         occurrences all number
    3
    1
    Injection site erythema
         subjects affected / exposed
    15 / 87 (17.24%)
    4 / 84 (4.76%)
         occurrences all number
    17
    5
    Oedema peripheral
         subjects affected / exposed
    13 / 87 (14.94%)
    8 / 84 (9.52%)
         occurrences all number
    13
    9
    Pain
         subjects affected / exposed
    8 / 87 (9.20%)
    3 / 84 (3.57%)
         occurrences all number
    9
    5
    Pyrexia
         subjects affected / exposed
    47 / 87 (54.02%)
    44 / 84 (52.38%)
         occurrences all number
    64
    64
    Fatigue
         subjects affected / exposed
    3 / 87 (3.45%)
    9 / 84 (10.71%)
         occurrences all number
    3
    9
    Localised oedema
         subjects affected / exposed
    2 / 87 (2.30%)
    3 / 84 (3.57%)
         occurrences all number
    3
    3
    Non-cardiac ehest pain
         subjects affected / exposed
    3 / 87 (3.45%)
    1 / 84 (1.19%)
         occurrences all number
    3
    1
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    4 / 87 (4.60%)
    2 / 84 (2.38%)
         occurrences all number
    5
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    7 / 87 (8.05%)
    11 / 84 (13.10%)
         occurrences all number
    7
    11
    Dyspnoea
         subjects affected / exposed
    9 / 87 (10.34%)
    7 / 84 (8.33%)
         occurrences all number
    10
    7
    Epistaxis
         subjects affected / exposed
    10 / 87 (11.49%)
    8 / 84 (9.52%)
         occurrences all number
    14
    9
    Oropharyngeal pain
         subjects affected / exposed
    6 / 87 (6.90%)
    4 / 84 (4.76%)
         occurrences all number
    7
    4
    Productive cough
         subjects affected / exposed
    3 / 87 (3.45%)
    3 / 84 (3.57%)
         occurrences all number
    3
    4
    Dysphonia
         subjects affected / exposed
    1 / 87 (1.15%)
    3 / 84 (3.57%)
         occurrences all number
    10
    7
    Pleural effusion
         subjects affected / exposed
    2 / 87 (2.30%)
    2 / 84 (2.38%)
         occurrences all number
    3
    2
    Psychiatric disorders
    Hallucination
         subjects affected / exposed
    0 / 87 (0.00%)
    3 / 84 (3.57%)
         occurrences all number
    0
    3
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    4 / 87 (4.60%)
    4 / 84 (4.76%)
         occurrences all number
    4
    4
    C-reactive protein increased
         subjects affected / exposed
    9 / 87 (10.34%)
    9 / 84 (10.71%)
         occurrences all number
    9
    9
    Platelet count decreased
         subjects affected / exposed
    7 / 87 (8.05%)
    10 / 84 (11.90%)
         occurrences all number
    14
    21
    White blood cell count decreased
         subjects affected / exposed
    10 / 87 (11.49%)
    7 / 84 (8.33%)
         occurrences all number
    10
    7
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 87 (1.15%)
    5 / 84 (5.95%)
         occurrences all number
    1
    5
    Blood bilirubin increased
         subjects affected / exposed
    0 / 87 (0.00%)
    4 / 84 (4.76%)
         occurrences all number
    0
    5
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 87 (0.00%)
    4 / 84 (4.76%)
         occurrences all number
    0
    4
    Injury, poisoning and procedural complications
    Refractoriness to platelet transfusion
         subjects affected / exposed
    14 / 87 (16.09%)
    4 / 84 (4.76%)
         occurrences all number
    14
    4
    Cardiac disorders
    Atrial tachycardia
         subjects affected / exposed
    3 / 87 (3.45%)
    2 / 84 (2.38%)
         occurrences all number
    3
    2
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    5 / 87 (5.75%)
    3 / 84 (3.57%)
         occurrences all number
    7
    3
    Headache
         subjects affected / exposed
    17 / 87 (19.54%)
    13 / 84 (15.48%)
         occurrences all number
    22
    14
    Tremor
         subjects affected / exposed
    3 / 87 (3.45%)
    1 / 84 (1.19%)
         occurrences all number
    3
    1
    Dysgeusia
         subjects affected / exposed
    1 / 87 (1.15%)
    4 / 84 (4.76%)
         occurrences all number
    1
    4
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    29 / 87 (33.33%)
    20 / 84 (23.81%)
         occurrences all number
    29
    20
    Febrile neutropenia
         subjects affected / exposed
    9 / 87 (10.34%)
    12 / 84 (14.29%)
         occurrences all number
    11
    14
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    4 / 87 (4.60%)
    2 / 84 (2.38%)
         occurrences all number
    4
    2
    Abdominal pain
         subjects affected / exposed
    4 / 87 (4.60%)
    2 / 84 (2.38%)
         occurrences all number
    4
    5
    Abdominal pain upper
         subjects affected / exposed
    5 / 87 (5.75%)
    9 / 84 (10.71%)
         occurrences all number
    5
    10
    Constipation
         subjects affected / exposed
    10 / 87 (11.49%)
    3 / 84 (3.57%)
         occurrences all number
    15
    4
    Diarrhoea
         subjects affected / exposed
    25 / 87 (28.74%)
    27 / 84 (32.14%)
         occurrences all number
    28
    31
    Dysphagia
         subjects affected / exposed
    3 / 87 (3.45%)
    2 / 84 (2.38%)
         occurrences all number
    5
    2
    Nausea
         subjects affected / exposed
    20 / 87 (22.99%)
    25 / 84 (29.76%)
         occurrences all number
    24
    29
    Stomatitis
         subjects affected / exposed
    22 / 87 (25.29%)
    22 / 84 (26.19%)
         occurrences all number
    22
    22
    Vomiting
         subjects affected / exposed
    15 / 87 (17.24%)
    12 / 84 (14.29%)
         occurrences all number
    19
    13
    Dyspepsia
         subjects affected / exposed
    3 / 87 (3.45%)
    2 / 84 (2.38%)
         occurrences all number
    3
    2
    Enteritis
         subjects affected / exposed
    4 / 87 (4.60%)
    0 / 84 (0.00%)
         occurrences all number
    4
    0
    Haemorrhoids
         subjects affected / exposed
    3 / 87 (3.45%)
    2 / 84 (2.38%)
         occurrences all number
    3
    2
    Asthenia
         subjects affected / exposed
    3 / 87 (3.45%)
    3 / 84 (3.57%)
         occurrences all number
    3
    3
    Proctalgia
         subjects affected / exposed
    3 / 87 (3.45%)
    0 / 84 (0.00%)
         occurrences all number
    3
    0
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    5 / 87 (5.75%)
    1 / 84 (1.19%)
         occurrences all number
    5
    1
    Petechia
         subjects affected / exposed
    9 / 87 (10.34%)
    8 / 84 (9.52%)
         occurrences all number
    9
    9
    Pruritus
         subjects affected / exposed
    6 / 87 (6.90%)
    0 / 84 (0.00%)
         occurrences all number
    6
    0
    Rash
         subjects affected / exposed
    7 / 87 (8.05%)
    7 / 84 (8.33%)
         occurrences all number
    8
    7
    Rash maculo-papular
         subjects affected / exposed
    5 / 87 (5.75%)
    5 / 84 (5.95%)
         occurrences all number
    5
    5
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    6 / 87 (6.90%)
    3 / 84 (3.57%)
         occurrences all number
    6
    3
    Bone pain
         subjects affected / exposed
    3 / 87 (3.45%)
    3 / 84 (3.57%)
         occurrences all number
    3
    3
    Myalgia
         subjects affected / exposed
    3 / 87 (3.45%)
    0 / 84 (0.00%)
         occurrences all number
    3
    0
    Pain in extremity
         subjects affected / exposed
    7 / 87 (8.05%)
    1 / 84 (1.19%)
         occurrences all number
    7
    1
    Infections and infestations
    Device related infection
         subjects affected / exposed
    8 / 87 (9.20%)
    1 / 84 (1.19%)
         occurrences all number
    8
    1
    Enterococcal infection
         subjects affected / exposed
    3 / 87 (3.45%)
    3 / 84 (3.57%)
         occurrences all number
    3
    3
    Nasapharyngitis
         subjects affected / exposed
    3 / 87 (3.45%)
    4 / 84 (4.76%)
         occurrences all number
    3
    4
    Bronchitis
         subjects affected / exposed
    3 / 87 (3.45%)
    2 / 84 (2.38%)
         occurrences all number
    3
    2
    Infection
         subjects affected / exposed
    3 / 87 (3.45%)
    1 / 84 (1.19%)
         occurrences all number
    4
    1
    Injection site infection
         subjects affected / exposed
    1 / 87 (1.15%)
    3 / 84 (3.57%)
         occurrences all number
    1
    3
    Lung infection
         subjects affected / exposed
    5 / 87 (5.75%)
    5 / 84 (5.95%)
         occurrences all number
    5
    5
    Weight increased
         subjects affected / exposed
    6 / 87 (6.90%)
    2 / 84 (2.38%)
         occurrences all number
    6
    2
    Sepsis
         subjects affected / exposed
    0 / 87 (0.00%)
    3 / 84 (3.57%)
         occurrences all number
    0
    3
    Staphylococcal infection
         subjects affected / exposed
    4 / 87 (4.60%)
    0 / 84 (0.00%)
         occurrences all number
    4
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    10 / 87 (11.49%)
    6 / 84 (7.14%)
         occurrences all number
    10
    6
    Hypokalaemia
         subjects affected / exposed
    8 / 87 (9.20%)
    5 / 84 (5.95%)
         occurrences all number
    9
    5

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Jul 2016
    Study protocol V3, dated 15.06.2016: Personnel-related changes; Further clarification on definitions and handling, Changes in the observation period for the endpoint "clinical refractoriness" and time point for temperature measurements. Patient Information and consent form V3, dated 15.06.2016: Implementation of genetic tests in case of expected TA-GvHD.
    22 Nov 2016
    Patient Information and consent form V4, dated 25.10.2016 were updated.
    07 Dec 2016
    Study protocol V4, dated 07.11.2016: Addition of new manufacturing site and trial sites. Further clarification on protocol definitions.
    12 Dec 2016
    Patient Information and consent form V5, dated 06.12.2016: Reimbursement of travel costs up to 50 €.
    23 Jan 2018
    Study protocol V5, dated 02.10.2017: Addition of manufacturing of apheresis derived PC at the manufacturing site in Frankfurt; Patients with planned allogeneic stem cell transplantation could be enrolled and treated with IMP until starting of the conditioning regime (Step 3); Personnel-related changes; Further clarification on study protocol definitions.
    19 Oct 2018
    Patient Information and consent form V6, dated 18.07.2018: Update in accordance to the new EU general data protection regulation.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat May 04 08:15:27 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA