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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   35513   clinical trials with a EudraCT protocol, of which   5839   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).
     
    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:
    Open-label Phase-4 study to examine the change of vision-related quality of life in subjects with diabetic macular edema (DME) during treatment with intravitreal injections of 2 mg aflibercept according to EU label for the first year of treatment

    Summary
    EudraCT number
    2014-005119-17
    Trial protocol
    HU   CZ   SK   IT   LT   ES   PT   FR   DE   AT   GB  
    Global end of trial date
    09 Aug 2017

    Results information
    Results version number
    v1(current)
    This version publication date
    12 Aug 2018
    First version publication date
    12 Aug 2018
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    BAY86-5321/17850
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02581995
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Bayer AG
    Sponsor organisation address
    Kaiser-Wilhelm-Allee, D-51368 Leverkusen, Germany,
    Public contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
    Scientific contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
    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
    09 Aug 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Aug 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to evaluate the change in vision-related quality of life (VRQoL) (National Eye Institute Visual Function Questionnaire-25 [NEI VFQ-25] total score) in subjects with diabetic macular edema (DME) during the first year of treatment with aflibercept according to the european union product information (EU-PI) for treatment of DME.
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Council for Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all subjects. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    19 Nov 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
    Canada: 20
    Country: Number of subjects enrolled
    Czech Republic: 42
    Country: Number of subjects enrolled
    Austria: 10
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 21
    Country: Number of subjects enrolled
    Hungary: 127
    Country: Number of subjects enrolled
    Italy: 36
    Country: Number of subjects enrolled
    Lithuania: 14
    Country: Number of subjects enrolled
    Poland: 94
    Country: Number of subjects enrolled
    Portugal: 30
    Country: Number of subjects enrolled
    Slovakia: 87
    Country: Number of subjects enrolled
    Spain: 53
    Country: Number of subjects enrolled
    Switzerland: 5
    Country: Number of subjects enrolled
    United Kingdom: 18
    Worldwide total number of subjects
    560
    EEA total number of subjects
    535
    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)
    272
    From 65 to 84 years
    285
    85 years and over
    3

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Study was conducted at multiple study centers in 14 countries, between 19 November 2015 (first subject first visit) and 09 August 2017 (last subject last visit).

    Pre-assignment
    Screening details
    Overall, 676 subjects were screened. Of them, 116 subjects did not complete screening: 100 failed screening; 8 withdrew, 1 had an adverse event, 1 subject was lost to follow-up and 6 were not assigned to treatment for other reasons. A total of 560 subjects were assigned to treatment and 31 subjects discontinued the study prematurely.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Aflibercept
    Arm description
    Subjects were treated according to the EU-PI for treatment of DME for the first year of treatment and received 1 dose of 2 mg aflibercept injected intravitreally (IVT) every 4 weeks for 5 consecutive doses, followed by dosing every 8 weeks thereafter until the end of the 52 week treatment period.
    Arm type
    Experimental

    Investigational medicinal product name
    Aflibercept
    Investigational medicinal product code
    BAY86-5321
    Other name
    Eylea
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    Subjects were treated according to the EU-PI for treatment of DME for the first year of treatment and received 1 dose of 2 mg aflibercept injected IVT every 4 weeks for 5 consecutive doses, followed by dosing every 8 weeks thereafter until the end of the 52 week treatment period.

    Number of subjects in period 1
    Aflibercept
    Started
    560
    Completed
    529
    Not completed
    31
         Death
    4
         Other
    3
         Physician decision
    1
         Adverse event
    6
         Withdrawal by subject
    12
         Lost to follow-up
    5

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Aflibercept
    Reporting group description
    Subjects were treated according to the EU-PI for treatment of DME for the first year of treatment and received 1 dose of 2 mg aflibercept injected intravitreally (IVT) every 4 weeks for 5 consecutive doses, followed by dosing every 8 weeks thereafter until the end of the 52 week treatment period.

    Reporting group values
    Aflibercept Total
    Number of subjects
    560 560
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    64.3 ± 9.3 -
    Sex: Female, Male
    Units: Subjects
        Female
    224 224
        Male
    336 336
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0
        Asian
    4 4
        Native Hawaiian or Other Pacific Islander
    0 0
        Black or African American
    3 3
        White
    519 519
        More than one race
    0 0
        Unknown or Not Reported
    34 34
    DRSS (Diabetic retinopathy severity score)
    The following severities are possible. 10 = Diabetic retinopathy (DR) absent, 14 = DR questionable, 15 = DR questionable, 20 = Microaneurysms only, 35 = Mild Non-proliferative diabetic retinopathy (NPDR), 43 = Moderate NPDR, 47 = Moderately severe NPDR, 53 = Severe NPDR, 61 = Mild Proliferative diabetic retinopathy (PDR), 65 = Moderate PDR, 71 = High-risk PDR, 75 = High-risk PDR, 81 = Advanced PDR: fundus partially obscured, center of macula attached, 85 = Advanced PDR: posterior fundus obscured, or center of macula detached, 90 = cannot grade, even sufficiently for level 81 or 85.
    Units: Subjects
        10 - DR absent
    0 0
        15 - DR questionable
    2 2
        35 - Mild NPDR
    148 148
        43 - Moderate NPDR
    185 185
        47 - Moderately severe NPDR
    153 153
        53 - Severe NPDR
    48 48
        61 - Mild PDR
    8 8
        65 - Moderate PDR
    8 8
        71 - High-risk PDR
    2 2
        90 - Cannot grade
    6 6
    Central Retinal Thickness (CRT)
    The CRT was recorded at the study eye only. Subjects received active treatment (intravitreal aflibercept) for the study eye and received close medical supervision.
    Units: microns
        arithmetic mean (standard deviation)
    464.81 ± 136.21 -
    Best Corrected Visual Acuity (BCVA)
    The BCVA was recorded at the study eye only. Subjects received active treatment (intravitreal aflibercept) for the study eye and received close medical supervision.
    Units: score on a scale
        arithmetic mean (standard deviation)
    61.5 ± 10.9 -
    NEI VFQ-25 total score
    The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. In this format scores represent the achieved percentage of the total possible score, example: a score of 50 represents 50% of the highest possible score.
    Units: score on a scale
        arithmetic mean (standard deviation)
    70.122 ± 19.243 -
    NEI VFQ-25 near activities subscale
    Items within each sub-scale are averaged together to create the 12 sub-scale Scores. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Sub-scales with at least one item answered can be used to generate a sub-scale score. Hence, scores represent the average for all items in the subscale that the respondent answered. Evaluating this parameter included subjects from the full analysis set (N= 553).
    Units: score on a scale
        arithmetic mean (standard deviation)
    62.967 ± 23.479 -
    NEI VFQ-25 distant activities subscale
    Items within each sub-scale are averaged together to create the 12 sub-scale Scores. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Sub-scales with at least one item answered can be used to generate a sub-scale score. Hence, scores represent the average for all items in the subscale that the respondent answered. Evaluating this parameter included subjects from the full analysis set (N= 553).
    Units: score on a scale
        arithmetic mean (standard deviation)
    71.964 ± 23.973 -
    Pre-injection Intraocular Pressure
    Units: millimeter of mercury (mmHg)
        arithmetic mean (standard deviation)
    16.2 ± 3.0 -
    Systolic Blood Pressure
    Units: millimeter of mercury (mmHg)
        arithmetic mean (standard deviation)
    138.1 ± 13.6 -
    Diastolic Blood Pressure
    Units: millimeter of mercury (mmHg)
        arithmetic mean (standard deviation)
    77.7 ± 9.4 -
    Heart Rate
    Units: beats per minute (beats/min)
        arithmetic mean (standard deviation)
    75.1 ± 10.1 -
    Body Temperature
    Units: celsius
        arithmetic mean (standard deviation)
    36.37 ± 0.38 -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Aflibercept
    Reporting group description
    Subjects were treated according to the EU-PI for treatment of DME for the first year of treatment and received 1 dose of 2 mg aflibercept injected intravitreally (IVT) every 4 weeks for 5 consecutive doses, followed by dosing every 8 weeks thereafter until the end of the 52 week treatment period.

    Subject analysis set title
    Full Analysis Set (FAS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    FAS included all subjects who received at least one injection of study drug and completed the baseline and at least one post-baseline NEI VFQ-25 questionnaire (N= 553).

    Subject analysis set title
    Safety analysis set (SAF)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    SAF included all subjects who received at least 1 injection of study drug (N= 560).

    Primary: Change from Baseline to Week 52 in NEI VFQ-25 Total Score

    Close Top of page
    End point title
    Change from Baseline to Week 52 in NEI VFQ-25 Total Score [1]
    End point description
    National eye institute 25-item visual function questionnaire (NEI VFQ-25) is a condition-specific measure which was designed to capture the specific impact of vision loss on health-related quality of life (HRQoL). The calculation for NEI VFQ-25 sub-scale scores and total score was performed according to the “NEI VFQ-25 Scoring Algorithm – August 2000”. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. In this format scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score.
    End point type
    Primary
    End point timeframe
    Baseline, Week 52
    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: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    Aflibercept
    Number of subjects analysed
    553 [2]
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    6.106 (5.303 to 6.909)
    Notes
    [2] - FAS
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 52 in the NEI VFQ 25 Near Activities Subscale

    Close Top of page
    End point title
    Change from Baseline to Week 52 in the NEI VFQ 25 Near Activities Subscale
    End point description
    NEI VFQ-25 is a condition-specific measure which was designed to capture the specific impact of vision loss on HRQoL. The calculation for NEI VFQ-25 sub-scale scores and total score was performed according to the “NEI VFQ-25 Scoring Algorithm – August 2000”. Items within each sub-scale are averaged together to create the 12 sub-scale Scores. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Sub-scales with at least one item answered can be used to generate a sub-scale score. Hence, scores represent the average for all items in the subscale that the respondent answered.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    Aflibercept
    Number of subjects analysed
    553 [3]
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    11.370 (10.108 to 12.632)
    Notes
    [3] - FAS
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 52 in the NEI VFQ 25 Distant Activities Subscale

    Close Top of page
    End point title
    Change from Baseline to Week 52 in the NEI VFQ 25 Distant Activities Subscale
    End point description
    NEI VFQ-25 is a condition-specific measure which was designed to capture the specific impact of vision loss on HRQoL. The calculation for NEI VFQ-25 sub-scale scores and total score was performed according to the “NEI VFQ-25 Scoring Algorithm – August 2000”. Items within each sub-scale are averaged together to create the 12 sub-scale Scores. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Sub-scales with at least one item answered can be used to generate a sub-scale score. Hence, scores represent the average for all items in the subscale that the respondent answered.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    Aflibercept
    Number of subjects analysed
    553 [4]
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    7.331 (6.118 to 8.545)
    Notes
    [4] - FAS
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 52 in Best Corrected Visual Acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] letter score])

    Close Top of page
    End point title
    Change from Baseline to Week 52 in Best Corrected Visual Acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] letter score])
    End point description
    Visual function was assessed using the ETDRS protocol (Early Treatment Diabetic Retinopathy Study Research Group 1985) starting at 4 meters. The values might range from 0 to 100. A higher score represents better functioning.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    Aflibercept
    Number of subjects analysed
    553 [5]
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    10.0 (9.5 to 10.6)
    Notes
    [5] - FAS
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 52 in Central Retinal Thickness (CRT) Measured by Optical Coherence Tomography (OCT)

    Close Top of page
    End point title
    Change from Baseline to Week 52 in Central Retinal Thickness (CRT) Measured by Optical Coherence Tomography (OCT)
    End point description
    The CRT was recorded at the study eye only. Subjects received active treatment (intravitreal aflibercept) for the study eye and received close medical supervision. Retinal and lesion characteristics were evaluated using spectral domain optical coherence tomography (OCT). For all visits where the OCT procedure was scheduled, images were captured and read by the investigator. All OCTs were electronically archived at the study sites as part of the source documentation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    Aflibercept
    Number of subjects analysed
    553 [6]
    Units: microns
        arithmetic mean (confidence interval 95%)
    -175.38 (-184.93 to -165.82)
    Notes
    [6] - FAS
    No statistical analyses for this end point

    Secondary: Proportion of Subjects Progressing to Greater or Equal to (>=) 61 on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) as Assessed by Fundus Photography (FP)

    Close Top of page
    End point title
    Proportion of Subjects Progressing to Greater or Equal to (>=) 61 on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) as Assessed by Fundus Photography (FP)
    End point description
    The ETDRS DRSS was assessed by FP according to the following scale for both eyes. The following severities are possible. 10 = Diabetic retinopathy (DR) absent, 14 = DR questionable, 15 = DR questionable, 20 = Micro-aneurysms only, 35 = Mild Non-proliferative diabetic retinopathy (NPDR), 43 = Moderate NPDR, 47 = Moderately severe NPDR, 53 = Severe NPDR, 61 = Mild Proliferative diabetic retinopathy (PDR), 65 = Moderate PDR, 71 = High-risk PDR, 75 = High-risk PDR, 81 = Advanced PDR: fundus partially obscured, center of macula attached, 85 = Advanced PDR: posterior fundus obscured, or center of macula detached, 90 = cannot grade, even sufficiently for level 81 or 85.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    Aflibercept
    Number of subjects analysed
    489 [7]
    Units: percentage of subjects
        number (not applicable)
    0.4
    Notes
    [7] - Subjects in the FAS with gradable baseline and Week 52 FP and a DRSS of less than (<) 61 at baseline
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in Pre-injection Intraocular Pressure for Study Eye Every 4 Weeks

    Close Top of page
    End point title
    Change from Baseline in Pre-injection Intraocular Pressure for Study Eye Every 4 Weeks
    End point description
    Intraocular pressure (IOP) was measured using applanation tonometry Goldmann, Tonopen or approved alternative). The same method of intraocular pressure measurement was used in each participant throughout the study. For the measurement of intraocular pressure, a local anesthetic combined with fluorescein was applied topically to the eye being tested (example: one drop of oxybuprocain plus fluorescein). In the below table, pre-injection intraocular pressure for study eye was reported and ‘n’ signifies number od subjects who were evaluable for this measure at given time point.
    End point type
    Other pre-specified
    End point timeframe
    Baseline, Weeks 4, 8, 12, 16, 24, 32, 40, 48, 52
    End point values
    Aflibercept
    Number of subjects analysed
    560 [8]
    Units: millimeter of mercury (mmHg)
    arithmetic mean (standard deviation)
        Change at Week 4 (n= 552)
    -0.4 ± 2.9
        Change at Week 8 (n= 545)
    -0.3 ± 2.9
        Change at Week 12 (n= 547)
    -0.5 ± 2.9
        Change at Week 16 (n= 548)
    -0.3 ± 2.9
        Change at Week 24 (n= 542)
    -0.2 ± 3.0
        Change at Week 32 (n= 541)
    -0.1 ± 3.0
        Change at Week 40 (n= 533)
    0.0 ± 3.0
        Change at Week 48 (n= 532)
    0.0 ± 3.0
        Change at Week 52 (n= 527)
    0.1 ± 3.1
    Notes
    [8] - SAF
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in Diastolic Blood Pressure at Week 52

    Close Top of page
    End point title
    Change from Baseline in Diastolic Blood Pressure at Week 52
    End point description
    Diastolic blood pressure was measured in a consistent and standardized way according to locally established practice.
    End point type
    Other pre-specified
    End point timeframe
    Baseline, Week 52
    End point values
    Aflibercept
    Number of subjects analysed
    560 [9]
    Units: millimeter of mercury (mmHg)
        arithmetic mean (standard deviation)
    -0.3 ± 9.9
    Notes
    [9] - SAF
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in Systolic Blood Pressure at Week 52

    Close Top of page
    End point title
    Change from Baseline in Systolic Blood Pressure at Week 52
    End point description
    Systolic blood pressure was measured in a consistent and standardized way according to locally established practice.
    End point type
    Other pre-specified
    End point timeframe
    Baseline, Week 52
    End point values
    Aflibercept
    Number of subjects analysed
    560 [10]
    Units: millimeter of mercury (mmHg)
        arithmetic mean (standard deviation)
    -0.1 ± 15.1
    Notes
    [10] - SAF
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in Heart Rate at Week 52

    Close Top of page
    End point title
    Change from Baseline in Heart Rate at Week 52
    End point description
    Heart rate was measured in a consistent and standardized way according to locally established practice.
    End point type
    Other pre-specified
    End point timeframe
    Baseline, Week 52
    End point values
    Aflibercept
    Number of subjects analysed
    560 [11]
    Units: beats per minute (beats/min)
        arithmetic mean (standard deviation)
    -1.0 ± 9.5
    Notes
    [11] - SAF
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in Body Temperature at Week 52

    Close Top of page
    End point title
    Change from Baseline in Body Temperature at Week 52
    End point description
    Temperature was measured in a consistent and standardized way according to locally established practice.
    End point type
    Other pre-specified
    End point timeframe
    Baseline, Week 52
    End point values
    Aflibercept
    Number of subjects analysed
    560 [12]
    Units: celsius
        arithmetic mean (standard deviation)
    -0.04 ± 0.41
    Notes
    [12] - SAF
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    From start of study treatment up to 30 days after the last injection of study treatment
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Aflibercept
    Reporting group description
    Subjects were treated according to the EU-PI for treatment of DME for the first year of treatment and received 1 dose of 2 mg aflibercept injected IVT every 4 weeks for 5 consecutive doses, followed by dosing every 8 weeks thereafter until the end of the 52 week treatment period.

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: There was no non-serious treatment-emergent adverse events reported by ≥ 5% of subjects.
    Serious adverse events
    Aflibercept
    Total subjects affected by serious adverse events
         subjects affected / exposed
    66 / 560 (11.79%)
         number of deaths (all causes)
    5
         number of deaths resulting from adverse events
    5
    Vascular disorders
    Peripheral arterial occlusive disease
         subjects affected / exposed
    2 / 560 (0.36%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Surgical and medical procedures
    Umbilical hernia repair
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vitrectomy
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder neoplasm
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metastases to lymph nodes
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metastases to peritoneum
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metastatic malignant melanoma
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    2 / 560 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Major depression
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    Prostatitis
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fracture
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Carbon monoxide poisoning
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rib fracture
         subjects affected / exposed
    2 / 560 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Inflammation of wound
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Echocardiogram abnormal
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Influenza A virus test positive
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Bundle branch block right
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    2 / 560 (0.36%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Cardiopulmonary failure
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Myocardial infarction
         subjects affected / exposed
    2 / 560 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Mitral valve incompetence
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiovascular insufficiency
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea exertional
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Lacunar stroke
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    3 / 560 (0.54%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular encephalopathy
         subjects affected / exposed
    2 / 560 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Eye disorders
    Cataract subcapsular
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Anterior chamber inflammation
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Posterior capsule opacification
         subjects affected / exposed
    2 / 560 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vitritis
         subjects affected / exposed
    2 / 560 (0.36%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Pancreatitis acute
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peptic ulcer haemorrhage
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Diabetic nephropathy
         subjects affected / exposed
    2 / 560 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    2 / 560 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Type 1 diabetes mellitus
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Boutonneuse fever
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 560 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Anal abscess
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Endophthalmitis
         subjects affected / exposed
    3 / 560 (0.54%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Diabetic foot infection
         subjects affected / exposed
    2 / 560 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Parotitis
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    6 / 560 (1.07%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    Pyelonephritis chronic
         subjects affected / exposed
    1 / 560 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 560 (0.18%)
         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
    Aflibercept
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 560 (0.00%)

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Sep 2015
    The following modifications were made in this amendment: •An update was made to inclusion criterion: use of adequate contraception (definition based on the judgment of the investigator) replaced with use of highly effective contraception (definition based clinical trials facilitation group [CTFG] from 15 September 2014) •Updates were made to pregnancy testing requirements: serum test binding was required at the screening visit (urine dipstick was not an alternative as per original protocol); urine dipstick test added for baseline visit. A requirement for serum pregnancy test within 7 days before first injection of medication was added •An update was made to inclusion criteria: “written informed consent” complemented by “signed” •Special warnings from EU-PI (most recent version number) were added to information on dosage and administration of the study drug •Smoking history was added to the medical history •Total and high-density lipoprotein cholesterol were added to the laboratory safety parameters

    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.
    IOP, AEs, vital signs in clinical trial application (CTA) (E.5.2) were not secondary endpoints of clinical study protocol (CSP). Proportion of subjects progressing to >= 61 ETDRS of DRSS was a secondary endpoint of the CSP missing in the CTA (E.5.2).
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA