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   43845   clinical trials with a EudraCT protocol, of which   7282   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:
    Intravitreal Aflibercept (Eylea®) for therapy of choroidal neovascularization and fibrovascular proliferation in patients with Pseudoxanthoma elasticum

    Summary
    EudraCT number
    		 2014-005263-33
    Trial protocol
    		 DE  
    Global end of trial date
    02 Jul 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Feb 2022
    First version publication date
    09 Feb 2022
    Other versions
    Summary report(s)
    		 Publication

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    AUG-201202-EyNeP
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02537054
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Universitätsklinikum Bonn
    Sponsor organisation address
    Venusberg-Campus 1, Bonn, Germany,
    Public contact
    Dr. med. Christoph Coch, Studienzentrale SZB, 0049 22828716040, ccoch@uni-bonn.de
    Scientific contact
    Dr. med. Christoph Coch, Studienzentrale SZB, 0049 22828716040, ccoch@uni-bonn.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
    19 Nov 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    02 Jul 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Jul 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to determine whether Aflibercept (Eylea) is effective in the treatment of choroidal neovascularization and fibrovascular proliferation in patients with pseudoxanthoma elasticum (PXE) in terms of preservation or improvement of visual acuity.
    Protection of trial subjects
    The study medication was authorized for the treatment of various retinal diseases before. Each patient was informed about the study in detail, the patient and the investigation signed the informed consent form. A patient's insurance was in place. Adverse events were documented regularly.
    Background therapy
    		 -
    Evidence for comparator
    		 The development of intravitreal anti-vascular endothelial growth factor (VEGF) agents has significantly improved the visual prognosis of patients with PXE-related CNV. Good evidence exists for the efficacy of intravitreal bevacizumab and ranibizumab. Another intravitreal VEGF inhibitor is aflibercept, which is a fusion protein of the extracellular domains of the VEGF receptor 1 and 2 and the Fc fragment of human IgG potentially blocking all isoforms of VEGF A and placental growth factor. The efficacy of intravitreal aflibercept is proven for CNV secondary to AMD and myopia. Evidence for efficacy for the treatment of CNV secondary to angioid streaks in PXE patients is limited to a few case reports. In addition, there is one small prospective study on ranibizumab-pretreated patients with a CNV secondary to angioid streaks reporting favorable outcomes, which, however, was not specific for PXE patients. Therefore, it was the aim of this study to prospectively investigate the use of intravitreal aflibercept for treatment-naïve and pretreated CNV in patients with PXE.
    Actual start date of recruitment
    01 May 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 15
    Worldwide total number of subjects
    15
    EEA total number of subjects
    15
    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)
    14
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patients were recruited between September 2015 and July 2017 at the Department of Ophthalmology, University of Bonn, which is a tertiary referral center for patients with PXE in Germany.

    Pre-assignment
    Screening details
    		 The inclusion criteria were the diagnosis of an active CNV secondary to PXE and age between 18 and 65 years. The diagnosis of PXE was based on typical ophthalmologic findings and confirmed by genetic testing.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Prospective, open-label, uncontrolled, non-randomized interventional clinical trial.

    Arms
    Arm title
    		 Single Arm
    Arm description
    		 This was a prospective, open-label, uncontrolled, non-randomized interventional clinical trial.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Aflibercept (2 mg)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    Intravitreal injection of 2 mg aflibercept

    Number of subjects in period 1
    		Single Arm
    Started
    15
    Completed
    15

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial Total
    Number of subjects
    		 15 15
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 14 14
        From 65-84 years
    		 1 1
        85 years and over
    		 0 0
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    		 53 (22 to 65) -
    Gender categorical
    Units: Subjects
        Female
    		 10 10
        Male
    		 5 5
    Subject analysis sets

    Subject analysis set title
    Full analysis
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The primary endpoint was change of BCVA after 12 months compared to baseline. Secondary outcomes were change compared to baseline of central retinal thickness, leakage from CNV, retinal sensitivity, and vision-related quality of life.

    Subject analysis sets values
    		 Full analysis
    Number of subjects
    15
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
    14
        From 65-84 years
    1
        85 years and over
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    53 (22 to 65)
    Gender categorical
    Units: Subjects
        Female
    10
        Male
    5

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Single Arm
    Reporting group description
    		 This was a prospective, open-label, uncontrolled, non-randomized interventional clinical trial.

    Subject analysis set title
    Full analysis
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The primary endpoint was change of BCVA after 12 months compared to baseline. Secondary outcomes were change compared to baseline of central retinal thickness, leakage from CNV, retinal sensitivity, and vision-related quality of life.

    Primary: Change of BCVA compared to baseline

    		 Close Top of page
    End point title
    		 Change of BCVA compared to baseline
    End point description
    End point type
    Primary
    End point timeframe
    12 months
    End point values
    		 Single Arm Full analysis
    Number of subjects analysed
    15
    15
    Units: Whole
    15
    15
    Attachments
    		 Untitled (Filename: EyNep.pdf)
    Statistical analysis title
    		 Statistical analysis
    Statistical analysis description
    Continuous outcome measures (BCVA, central retinal thickness, retinal sensitivity, and quality of life) at baseline and month 12 are described using means and standard deviations (SD). Mean differences between baseline and month 12 were calculated along with 95% confidence intervals. The measures at the two points in time were compared using Wilcoxon rank-sum tests. A two-sided p < 0.05 was considered significant.
    Comparison groups
    Single Arm v Full analysis
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.05
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Change of central retinal thickness, leakage from CNV, retinal sensitivity, vision-related quality of life

    		 Close Top of page
    End point title
    		 Change of central retinal thickness, leakage from CNV, retinal sensitivity, vision-related quality of life
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Single Arm Full analysis
    Number of subjects analysed
    15
    15
    Units: Whole
    15
    15
    Attachments
    		 Untitled (Filename: EyNep.pdf)
    Statistical analysis title
    		 Statistical analysis
    Statistical analysis description
    Continuous outcome measures (BCVA, central retinal thickness, retinal sensitivity, and quality of life) at baseline and month 12 are described using means and standard deviations (SD). Mean differences between baseline and month 12 were calculated along with 95% confidence intervals. The measures at the two points in time were compared using Wilcoxon rank-sum tests. A two-sided p < 0.05 was considered significant.
    Comparison groups
    Single Arm v Full analysis
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.05
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Statistical analysis
    Statistical analysis description
    Continuous outcome measures (BCVA, central retinal thickness, retinal sensitivity, and quality of life) at baseline and month 12 are described using means and standard deviations (SD). Mean differences between baseline and month 12 were calculated along with 95% confidence intervals. The measures at the two points in time were compared using Wilcoxon rank-sum tests. A two-sided p < 0.05 was considered significant.
    Comparison groups
    Single Arm v Full analysis
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.05
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Statistical analysis
    Statistical analysis description
    Continuous outcome measures (BCVA, central retinal thickness, retinal sensitivity, and quality of life) at baseline and month 12 are described using means and standard deviations (SD). Mean differences between baseline and month 12 were calculated along with 95% confidence intervals. The measures at the two points in time were compared using Wilcoxon rank-sum tests. A two-sided p < 0.05 was considered significant.
    Comparison groups
    Single Arm v Full analysis
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.05
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Statistical analysis
    Statistical analysis description
    Differences regarding leakage from a CNV on FA were compared using a McNemar test.
    Comparison groups
    Single Arm v Full analysis
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.05
    Method
    		 Mcnemar
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    September 2015 - July 2017
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Entire Cohort
    Reporting group description
    		 -

    Serious adverse events
    		 Entire Cohort
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 15 (13.33%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    Surgical and medical procedures
    Intracardiac catheter after an ST-elevation on ERG examination
    Additional description: The causality with the study medication/procedure was graded as unlikely.
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Surgery for an umbilical hernia
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Entire Cohort
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 15 (33.33%)
    Eye disorders
    Ocular adverse events
    Additional description: 5 ocular adverse events were documented that were likely associated with the study medication/procedure (increased intraocular pressure in 2 participants, mild conjunctival hemorrhage in 2 participants and foreign body sensation after injection in 1.
         subjects affected / exposed
    5 / 15 (33.33%)
         occurrences all number
    5

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/31863395
    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-Fri Apr 19 00:15:25 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA