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    Clinical Trial Results:
    Treating neovascular age-related Macular Degeneration with Aflibercept:A multi-centre randomized controlled trial comparing Standard Care with an individualised Treat and Extend regimen.

    Summary
    EudraCT number
    		 2015-002302-36
    Trial protocol
    		 GB  
    Global end of trial date
    26 Feb 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Mar 2022
    First version publication date
    01 Mar 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MATE2015
    Additional study identifiers
    ISRCTN number
    		 ISRCTN58955026
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    York and Scarborough Teaching Hospital NHS Foundation Trust
    Sponsor organisation address
    Wigginton Road, York, United Kingdom, YO31 8HE
    Public contact
    Deborah Phillips, York and Scarborough Teaching Hospital NHS Foundation Trust, 44 01904725123, deborah.phillips@york.nhs.uk
    Scientific contact
    Deborah Phillips, York and Scarborough Teaching Hospital NHS Foundation Trust, 44 01904725123, deborah.phillips@york.nhs.uk
    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
    26 Feb 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    26 Feb 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Feb 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Outcome 1. The main objective of the study is to determine if a multicentered phase 3 randomised control trial comparing two treatment regimens of Aflibercept for neovascular age related macular degeneration be safely and effectively conducted and delivered. Outcome 2. Long term (4 years) changes in visual acuity and the central thickness of the retina. Also focusing on the number of injections and visits in each group
    Protection of trial subjects
    No trial specific measures were required for trial subject protection beyond those of standard NHS care.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Jan 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
    United Kingdom: 40
    Worldwide total number of subjects
    40
    EEA total number of subjects
    0
    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)
    0
    From 65 to 84 years
    29
    85 years and over
    11

    Subject disposition

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    Recruitment
    Recruitment details
    		 Recruitment took place across 6 NHS Trusts in England. between December 2015 and January 2017.

    Pre-assignment
    Screening details
    		 93 participants were approached to take part 49 excluded: 10 didn't meet inclusion criteria, 29 declined to participate, 10 excluded for other reasons. 44 randomised evenly but 4 withdrawn by Sponsor as eligibility couldn't be confirmed so weren't included in analysis. 40 participants included in final analysis.

    Period 1
    Period 1 title
    MATE study
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Single blind
    Roles blinded
    		 Assessor [1]
    Blinding implementation details
    Optometrists assessing visual acuity were blinded to the study arm

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Standard Care
    Arm description
    		 Receive standard care treatment with Aflibercept for neovascular AMD as recommended by NICE in the NHS Ophthalmology clinics
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Eylea 40 mg/ml solution for injection in a vial.
    Investigational medicinal product code
    Other name
    Aflibercept
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    2mg (0.05mL) of aflibercept administered by intravitreal injection at specified intervals during the trial. Should not be administered more frequently than every 28 days.

    Arm title
    		 Treat and Extend
    Arm description
    		 Individualised treat and extend regimen
    Arm type
    		 Experimental

    Investigational medicinal product name
    Eylea 40 mg/ml solution for injection in a vial.
    Investigational medicinal product code
    Other name
    Aflibercept
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    2mg (0.05mL) of aflibercept administered by intravitreal injection at specified intervals during the trial. Should not be administered more frequently than every 28 days.

    Notes
    [1] - The roles blinded appear inconsistent with a simple blinded trial.
    Justification: The optometrists assessing the participants visual acuity were blinded to the study arm to avoid unintentional bias when performing assessments.
    Number of subjects in period 1
    		Standard Care Treat and Extend
    Started
    20
    20
    12 Months
    19
    20
    Completed
    16
    18
    Not completed
    4
    2
         Consent withdrawn by subject
    3
    1
         Lost to follow-up due to death
    1
    1
    Period 2
    Period 2 title
    MATE 2
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    Optometrist blinded to treatment allocation.

    Arms
    Arm title
    		 Extension
    Arm description
    		 All participants who consented to the extension study to evaluate the long term outcomes and burden on patients and services
    Arm type
    		 Single Arm

    Investigational medicinal product name
    Eylea 40 mg/ml solution for injection in a vial.
    Investigational medicinal product code
    Other name
    Aflibercept
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    2mg (0.05mL) of aflibercept administered by intravitreal injection at specified intervals during the trial. Should not be administered more frequently than every 28 days.

    Number of subjects in period 2 [2]
    		Extension
    Started
    26
    36 Month
    24
    Completed
    21
    Not completed
    5
         Consent withdrawn by subject
    1
         Physician decision
    2
         Lost to follow-up due to death
    2
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Participants in the preceding period were asked to reconsent to continue into the extension study for a further 2 years. Only those who consented to continue were included in period 2.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Standard Care
    Reporting group description
    		 Receive standard care treatment with Aflibercept for neovascular AMD as recommended by NICE in the NHS Ophthalmology clinics

    Reporting group title
    Treat and Extend
    Reporting group description
    		 Individualised treat and extend regimen

    Reporting group values
    		 Standard Care Treat and Extend Total
    Number of subjects
    		 20 20 40
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Baseline demographics
    Units: years
        arithmetic mean (standard deviation)
    		 78.98 ( 7.7 ) 78.4 ( 6.5 ) -
    Gender categorical
    Units: Subjects
        Female
    		 11 11 22
        Male
    		 9 9 18
    VA Baseline
    Best corrected visual acuity at baseline
    Units: ETDRS letters
        arithmetic mean (standard deviation)
    		 60.8 ( 12.5 ) 63.6 ( 10.0 ) -
    CRT Baseline
    Central retinal Thickness
    Units: µm
        arithmetic mean (standard deviation)
    		 414.3 ( 144.5 ) 406.6 ( 114.6 ) -
    MacDQoL Baseline
    MacDQoL Average weighted impact score at baseline
    Units: AWI
        arithmetic mean (standard deviation)
    		 -2.4 ( 1.7 ) -2.5 ( 2.0 ) -
    MacTSQ Baseline
    MacTSQ total score
    Units: MacTSQ single scale score
        arithmetic mean (standard deviation)
    		 66.9 ( 4.5 ) 64.2 ( 9.2 ) -
    Subject analysis sets

    Subject analysis set title
    Extension
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants who consented to continue into the MATE extension at their 24 month visit.

    Subject analysis sets values
    		 Extension
    Number of subjects
    26
    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)
        From 65-84 years
        85 years and over
    Age continuous
    Baseline demographics
    Units: years
        arithmetic mean (standard deviation)
    77.1 ( 6.6 )
    Gender categorical
    Units: Subjects
        Female
    15
        Male
    11
    VA Baseline
    Best corrected visual acuity at baseline
    Units: ETDRS letters
        arithmetic mean (standard deviation)
    60.7 ( 11.4 )
    CRT Baseline
    Central retinal Thickness
    Units: µm
        arithmetic mean (standard deviation)
    423.7 ( 134.2 )
    MacDQoL Baseline
    MacDQoL Average weighted impact score at baseline
    Units: AWI
        arithmetic mean (standard deviation)
    -2.1 ( 1.7 )
    MacTSQ Baseline
    MacTSQ total score
    Units: MacTSQ single scale score
        arithmetic mean (standard deviation)
    67.2 ( 4.5 )

    End points

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    End points reporting groups
    Reporting group title
    Standard Care
    Reporting group description
    		 Receive standard care treatment with Aflibercept for neovascular AMD as recommended by NICE in the NHS Ophthalmology clinics

    Reporting group title
    Treat and Extend
    Reporting group description
    		 Individualised treat and extend regimen
    Reporting group title
    Extension
    Reporting group description
    		 All participants who consented to the extension study to evaluate the long term outcomes and burden on patients and services

    Subject analysis set title
    Extension
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants who consented to continue into the MATE extension at their 24 month visit.

    Primary: Change in ETDRS visual acuity at 36 months

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    End point title
    		 Change in ETDRS visual acuity at 36 months
    End point description
    Mean change in ETDRS visual acuity at 36 months
    End point type
    Primary
    End point timeframe
    36 Month Visit data, defined as either the visit occurring immediately after the 3 year anniversary for the participant, or a visit within 7 days of the 3 year anniversary.
    End point values
    		 Extension Extension
    Number of subjects analysed
    22
    22
    Units: ETDRS Letters
        arithmetic mean (standard deviation)
    -1.1 ( 24.3 )
    -1.1 ( 24.3 )
    Statistical analysis title
    		 Change in ETDRS letters at 36 months
    Statistical analysis description
    Change in ETDRS visual acuity from baseline at 36 months.
    Comparison groups
    Extension v Extension
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.833
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Primary: Change in ETDRS visual acuity at 48 months

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    End point title
    		 Change in ETDRS visual acuity at 48 months
    End point description
    Mean change in ETDRS visual acuity at 48 months
    End point type
    Primary
    End point timeframe
    48 Month Visit data, defined as either the visit occurring immediately after the 4 year anniversary for the participant, or a visit within 7 days of the 4 year anniversary.
    End point values
    		 Extension Extension
    Number of subjects analysed
    20
    20
    Units: EDTRS letters
        arithmetic mean (standard deviation)
    4.5 ( 21.6 )
    4.5 ( 21.6 )
    Statistical analysis title
    		 Change in ETDRS letters at 48 months
    Statistical analysis description
    Change in ETDRS visual acuity from baseline at 48 months
    Comparison groups
    Extension v Extension
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 = 0.212
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [1] - Single arm study

    Primary: Patients gaining or losing more than or equal to 15 ETDRS letters at 36 months

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    End point title
    		 Patients gaining or losing more than or equal to 15 ETDRS letters at 36 months [2]
    End point description
    End point type
    Primary
    End point timeframe
    36 Month Visit data, defined as either the visit occurring immediately after the 3 year anniversary for the participant, or a visit within 7 days of the 3 year anniversary.
    Notes
    [2] - 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 only for this analysis
    End point values
    		 Extension
    Number of subjects analysed
    22
    Units: Number of patients
        Loss of 15 or more letters
    6
        Change of -14 to 14 letters
    11
        Gain of 15 or more letters
    5
    No statistical analyses for this end point

    Primary: Patients gaining or losing more than or equal to 15 ETDRS letters at 48 months

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    End point title
    		 Patients gaining or losing more than or equal to 15 ETDRS letters at 48 months [3]
    End point description
    End point type
    Primary
    End point timeframe
    48 Month Visit data, defined as either the visit occurring immediately after the 4 year anniversary for the participant, or a visit within 7 days of the 4 year anniversary.
    Notes
    [3] - 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 only for this analysis
    End point values
    		 Extension
    Number of subjects analysed
    20
    Units: Number of patients
        Loss of 15 or more letters
    4
        Change of -14 to 14 letters
    8
        Gain of 15 or more letters
    8
    No statistical analyses for this end point

    Primary: Change in CRT at 36 months

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    End point title
    		 Change in CRT at 36 months
    End point description
    End point type
    Primary
    End point timeframe
    36 Month Visit data, defined as either the visit occurring immediately after the 3 year anniversary for the participant, or a visit within 7 days of the 3 year anniversary.
    End point values
    		 Extension Extension
    Number of subjects analysed
    24
    24
    Units: µm
        arithmetic mean (standard deviation)
    -183.8 ( 138.3 )
    -183.8 ( 138.3 )
    Statistical analysis title
    		 CRT change from baseline at 36 months
    Statistical analysis description
    Change in CRT from baseline at 36 months
    Comparison groups
    Extension v Extension
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    		 other [4]
    P-value
    		 = 183.8
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [4] - Single arm

    Primary: Change in CRT at 48 months

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    End point title
    		 Change in CRT at 48 months
    End point description
    End point type
    Primary
    End point timeframe
    48 Month Visit data, defined as either the visit occurring immediately after the 4 year anniversary for the participant, or a visit within 7 days of the 4 year anniversary.
    End point values
    		 Extension Extension
    Number of subjects analysed
    21
    21
    Units: µm
        arithmetic mean (standard deviation)
    -134.1 ( 152.7 )
    -134.1 ( 152.7 )
    Statistical analysis title
    		 Change in CRT at 48 months
    Statistical analysis description
    Change in Central retinal thickness (CRT) from baseline at 48 months
    Comparison groups
    Extension v Extension
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 other [5]
    P-value
    		 = 0.002
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [5] - Single Arm

    Primary: Number of treatments in the study eye at 36 months

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    End point title
    		 Number of treatments in the study eye at 36 months [6]
    End point description
    End point type
    Primary
    End point timeframe
    36 Month Visit data, defined as either the visit occurring immediately after the 3 year anniversary for the participant, or a visit within 7 days of the 3 year anniversary.
    Notes
    [6] - 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 only for this analysis
    End point values
    		 Extension
    Number of subjects analysed
    26
    Units: Treatments
        arithmetic mean (standard deviation)
    23.8 ( 5.5 )
    No statistical analyses for this end point

    Primary: Number of treatments in the study eye at 48 months

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    End point title
    		 Number of treatments in the study eye at 48 months [7]
    End point description
    End point type
    Primary
    End point timeframe
    48 Month Visit data, defined as either the visit occurring immediately after the 4 year anniversary for the participant, or a visit within 7 days of the 4 year anniversary.
    Notes
    [7] - 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 only for this analysis
    End point values
    		 Extension
    Number of subjects analysed
    23
    Units: Treatments
        arithmetic mean (standard deviation)
    27.9 ( 8.5 )
    No statistical analyses for this end point

    Primary: Number of visits for the study eye at 36 months

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    End point title
    		 Number of visits for the study eye at 36 months [8]
    End point description
    End point type
    Primary
    End point timeframe
    36 Month Visit data, defined as either the visit occurring immediately after the 3 year anniversary for the participant, or a visit within 7 days of the 3 year anniversary.
    Notes
    [8] - 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 only for this analysis
    End point values
    		 Extension
    Number of subjects analysed
    26
    Units: Visits
        arithmetic mean (standard deviation)
    24.5 ( 4.7 )
    No statistical analyses for this end point

    Primary: Number of visits for the study eye at 48 months

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    End point title
    		 Number of visits for the study eye at 48 months [9]
    End point description
    End point type
    Primary
    End point timeframe
    48 Month Visit data, defined as either the visit occurring immediately after the 4 year anniversary for the participant, or a visit within 7 days of the 4 year anniversary.
    Notes
    [9] - 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 only for this analysis
    End point values
    		 Extension
    Number of subjects analysed
    23
    Units: Visits
        arithmetic mean (standard deviation)
    30.0 ( 6.6 )
    No statistical analyses for this end point

    Primary: Change in Mac DQoL at 36 months

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    End point title
    		 Change in Mac DQoL at 36 months
    End point description
    Mean change in MacDQoL average weighted impact score (AWI)
    End point type
    Primary
    End point timeframe
    36 Month Visit data, defined as either the visit occurring immediately after the 3 year anniversary for the participant, or a visit within 7 days of the 3 year anniversary.
    End point values
    		 Extension Extension
    Number of subjects analysed
    23
    23
    Units: Mac DQoL score
        arithmetic mean (standard deviation)
    -0.2 ( 1.7 )
    -0.2 ( 1.7 )
    Statistical analysis title
    		 Change in MacDQoL AWI at 36 months
    Statistical analysis description
    Change in MacDQoL Average Weighted Impact Score (AWI) at 36 month visit.
    Comparison groups
    Extension v Extension
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.375
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Primary: Change in Mac DQoL at 48 months

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    End point title
    		 Change in Mac DQoL at 48 months
    End point description
    Mean change in MacDQoL average weighted impact score (AWI)
    End point type
    Primary
    End point timeframe
    48 Month Visit data, defined as either the visit occurring immediately after the 4 year anniversary for the participant, or a visit within 7 days of the 4 year anniversary.
    End point values
    		 Extension Extension
    Number of subjects analysed
    22
    22
    Units: AWI score
        arithmetic mean (standard deviation)
    -0.3 ( 2.1 )
    -0.3 ( 2.1 )
    Statistical analysis title
    		 Change in MacDQoL AWI at 48 Months
    Statistical analysis description
    Change in MacDQoL Average Weighted Impact Score (AWI) at 48 month visit.
    Comparison groups
    Extension v Extension
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 other [10]
    P-value
    		 = 0.375
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [10] - Single Arm

    Primary: Change in MacTSQ at 36 months

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    End point title
    		 Change in MacTSQ at 36 months
    End point description
    Mean change in MacTSQ total score
    End point type
    Primary
    End point timeframe
    36 Month Visit data, defined as either the visit occurring immediately after the 3 year anniversary for the participant, or a visit within 7 days of the 3 year anniversary.
    End point values
    		 Extension Extension
    Number of subjects analysed
    18
    18
    Units: MacTSQ score
        arithmetic mean (standard deviation)
    0.9 ( 2.8 )
    0.9 ( 2.8 )
    Statistical analysis title
    		 Change in MacTSQ score at 36 months
    Statistical analysis description
    Change from baseline in MacTSQ total score at 36 month visit
    Comparison groups
    Extension v Extension
    Number of subjects included in analysis
    36
    Analysis specification
    Pre-specified
    Analysis type
    		 other [11]
    P-value
    		 = 0.462
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [11] - Single Arm

    Primary: Change in MacTSQ at 48 months

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    End point title
    		 Change in MacTSQ at 48 months
    End point description
    Mean change in MacTSQ Total score
    End point type
    Primary
    End point timeframe
    48 Month Visit data, defined as either the visit occurring immediately after the 4 year anniversary for the participant, or a visit within 7 days of the 4 year anniversary.
    End point values
    		 Extension Extension
    Number of subjects analysed
    16
    16
    Units: MacTSQ score
        arithmetic mean (standard deviation)
    1.2 ( 3.6 )
    1.2 ( 3.6 )
    Statistical analysis title
    		 Change in MacTSQ score at 48 months
    Statistical analysis description
    Change in MacTSQ total score from baseline at 48 month visit
    Comparison groups
    Extension v Extension
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [12]
    P-value
    		 = 0.232
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [12] - Single arm

    Secondary: Change in ETDRS visual acuity at 12 months

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    End point title
    		 Change in ETDRS visual acuity at 12 months
    End point description
    Mean Change in ETDRS visual acuity at 12 months
    End point type
    Secondary
    End point timeframe
    12 Month Visit data, defined as either the visit occurring immediately after the 1 year anniversary for the participant, or a visit within 7 days of the 1 year anniversary.
    End point values
    		 Standard Care Treat and Extend Extension
    Number of subjects analysed
    19
    20
    26
    Units: ETDRS Letters
        arithmetic mean (standard deviation)
    0.7 ( 18.6 )
    5.7 ( 15.6 )
    3.6 ( 5.5 )
    No statistical analyses for this end point

    Secondary: Change in ETDRS visual acuity at 24 months

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    End point title
    		 Change in ETDRS visual acuity at 24 months
    End point description
    Mean change in ETDRS visual acuity at 24 months
    End point type
    Secondary
    End point timeframe
    24 Month Visit data, defined as either the visit occurring immediately after the 2 year anniversary for the participant, or a visit within 7 days of the 2 year anniversary.
    End point values
    		 Standard Care Treat and Extend Extension
    Number of subjects analysed
    17
    18
    26
    Units: ETDRS Letters
        arithmetic mean (standard deviation)
    -2.4 ( 23.6 )
    2.9 ( 19.2 )
    1.2 ( 21.2 )
    No statistical analyses for this end point

    Secondary: Patients gaining or losing more than or equal to 15 ETDRS letters at 12 months

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    End point title
    		 Patients gaining or losing more than or equal to 15 ETDRS letters at 12 months
    End point description
    Percentage of patients gaining or losing more than or equal to 15 ETDRS letters at 12 months
    End point type
    Secondary
    End point timeframe
    12 Month Visit data, defined as either the visit occurring immediately after the 1 year anniversary for the participant, or a visit within 7 days of the 1 year anniversary.
    End point values
    		 Standard Care Treat and Extend Extension
    Number of subjects analysed
    19
    20
    26
    Units: Number of patients
        Loss of 15 or more letters
    5
    6
    5
        Change of -14 to 14 letters
    9
    12
    13
        Gain or 15 or more letters
    5
    2
    8
    No statistical analyses for this end point

    Secondary: Patients gaining or losing more than or equal to 15 ETDRS letters at 24 months

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    End point title
    		 Patients gaining or losing more than or equal to 15 ETDRS letters at 24 months
    End point description
    End point type
    Secondary
    End point timeframe
    24 Month Visit data, defined as either the visit occurring immediately after the 2 year anniversary for the participant, or a visit within 7 days of the 2 year anniversary.
    End point values
    		 Standard Care Treat and Extend Extension
    Number of subjects analysed
    19
    20
    26
    Units: Number of patients
        Loss of 15 or more letters
    5
    2
    7
        Change of -14 to 14 letters
    9
    12
    13
        Gain of 15 or more letters
    5
    6
    6
    No statistical analyses for this end point

    Secondary: Change in CRT at 12 months

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    End point title
    		 Change in CRT at 12 months
    End point description
    End point type
    Secondary
    End point timeframe
    12 Month Visit data, defined as either the visit occurring immediately after the 1 year anniversary for the participant, or a visit within 7 days of the 1 year anniversary.
    End point values
    		 Standard Care Treat and Extend Extension
    Number of subjects analysed
    19
    20
    26
    Units: µm
        arithmetic mean (standard deviation)
    -116.5 ( 111.2 )
    -147.8 ( 104.0 )
    -136.5 ( 115.0 )
    No statistical analyses for this end point

    Secondary: Change in CRT at 24 months

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    End point title
    		 Change in CRT at 24 months
    End point description
    End point type
    Secondary
    End point timeframe
    24 Month Visit data, defined as either the visit occurring immediately after the 2 year anniversary for the participant, or a visit within 7 days of the 2 year anniversary.
    End point values
    		 Standard Care Treat and Extend Extension
    Number of subjects analysed
    17
    18
    26
    Units: µm
        arithmetic mean (standard deviation)
    -148.8 ( 122.5 )
    -164.8 ( 117.8 )
    -138.6 ( 115.0 )
    No statistical analyses for this end point

    Secondary: Number of treatments in the study eye at 12 months

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    End point title
    		 Number of treatments in the study eye at 12 months
    End point description
    End point type
    Secondary
    End point timeframe
    12 Month Visit data, defined as either the visit occurring immediately after the 1 year anniversary for the participant, or a visit within 7 days of the 1 year anniversary.
    End point values
    		 Standard Care Treat and Extend Extension
    Number of subjects analysed
    19
    20
    26
    Units: Treatments
        arithmetic mean (standard deviation)
    8.3 ( 0.7 )
    9.5 ( 1.8 )
    9.3 ( 1.4 )
    No statistical analyses for this end point

    Secondary: Number of treatments in the study eye at 24 months

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    End point title
    		 Number of treatments in the study eye at 24 months
    End point description
    End point type
    Secondary
    End point timeframe
    24 Month Visit data, defined as either the visit occurring immediately after the 2 year anniversary for the participant, or a visit within 7 days of the 2 year anniversary.
    End point values
    		 Standard Care Treat and Extend Extension
    Number of subjects analysed
    17
    18
    26
    Units: Treatments
        arithmetic mean (standard deviation)
    17.3 ( 2.0 )
    16.4 ( 3.8 )
    17.3 ( 2.9 )
    No statistical analyses for this end point

    Secondary: Number of visits for the study eye at 12 months

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    End point title
    		 Number of visits for the study eye at 12 months
    End point description
    End point type
    Secondary
    End point timeframe
    12 Month Visit data, defined as either the visit occurring immediately after the 1 year anniversary for the participant, or a visit within 7 days of the 1 year anniversary.
    End point values
    		 Standard Care Treat and Extend Extension
    Number of subjects analysed
    19
    20
    26
    Units: Number of Visits
        arithmetic mean (standard deviation)
    8.3 ( 0.7 )
    9.5 ( 1.8 )
    9.3 ( 1.4 )
    No statistical analyses for this end point

    Secondary: Number of visits for the study eye at 24 months

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    End point title
    		 Number of visits for the study eye at 24 months
    End point description
    End point type
    Secondary
    End point timeframe
    24 Month Visit data, defined as either the visit occurring immediately after the 2 year anniversary for the participant, or a visit within 7 days of the 2 year anniversary.
    End point values
    		 Standard Care Treat and Extend Extension
    Number of subjects analysed
    17
    18
    26
    Units: Visits
        arithmetic mean (standard deviation)
    17.3 ( 2.0 )
    16.4 ( 3.8 )
    17.4 ( 2.9 )
    No statistical analyses for this end point

    Secondary: Change in Mac DQoL at 12 months

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    End point title
    		 Change in Mac DQoL at 12 months
    End point description
    Mean change in MacDQoL average weighted impact score (AWI)
    End point type
    Secondary
    End point timeframe
    12 Month Visit data, defined as either the visit occurring immediately after the 1 year anniversary for the participant, or a visit within 7 days of the 1 year anniversary.
    End point values
    		 Standard Care Treat and Extend Extension
    Number of subjects analysed
    18
    19
    26
    Units: Mac DQoL
        arithmetic mean (standard deviation)
    0.1 ( 1.9 )
    -1.1 ( 2.1 )
    0.4 ( 2.0 )
    No statistical analyses for this end point

    Secondary: Change in Mac DQoL at 24 months

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    End point title
    		 Change in Mac DQoL at 24 months
    End point description
    Mean change in MacDQoL average weighted impact score (AWI)
    End point type
    Secondary
    End point timeframe
    24 Month Visit data, defined as either the visit occurring immediately after the 2 year anniversary for the participant, or a visit within 7 days of the 2 year anniversary.
    End point values
    		 Standard Care Treat and Extend Extension
    Number of subjects analysed
    16
    18
    26
    Units: Mac DQoL score
        arithmetic mean (standard deviation)
    0.3 ( 1.7 )
    -0.1 ( 2.1 )
    -0.4 ( 1.9 )
    No statistical analyses for this end point

    Secondary: Change in MacTSQ at 12 months

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    End point title
    		 Change in MacTSQ at 12 months
    End point description
    Mean change in MacTSQ Total score
    End point type
    Secondary
    End point timeframe
    12 Month Visit data, defined as either the visit occurring immediately after the 1 year anniversary for the participant, or a visit within 7 days of the 1 year anniversary.
    End point values
    		 Standard Care Treat and Extend Extension
    Number of subjects analysed
    14
    15
    20
    Units: MacTSQ score
        arithmetic mean (standard deviation)
    1.7 ( 4.2 )
    3.7 ( 14.2 )
    -0.6 ( 5.1 )
    No statistical analyses for this end point

    Secondary: Change in MacTSQ at 24 months

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    End point title
    		 Change in MacTSQ at 24 months
    End point description
    Mean change in MacTSQ total score
    End point type
    Secondary
    End point timeframe
    24 Month Visit data, defined as either the visit occurring immediately after the 2 year anniversary for the participant, or a visit within 7 days of the 2 year anniversary.
    End point values
    		 Standard Care Treat and Extend Extension
    Number of subjects analysed
    12
    12
    20
    Units: MacTSQ score
        arithmetic mean (standard deviation)
    0.4 ( 4.6 )
    -0.9 ( 6.1 )
    0.7 ( 5.5 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Enrolment through to end of study, either 24 or 48 months later.
    Adverse event reporting additional description
    Adverse events were self-reported by participants upon prompts from the research team. Participants were asked if they'd experienced any perceived change to vision or perceived distortions in the study eye since the previous visit, any reported worsening was reported as an adverse event.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Standard Care
    Reporting group description
    		 Participants receiving treatment according to the standard care within the NHS. Phase 1: Monthly treatments for 3 consecutive visits Phase 2: 8 weekly treatment until the end of year one Phase 3: Treatment intervals may be extended or reduced by 2 weeks at the discretion of the treating physician. Minimum shortened duration of 4 weeks and maximum duration capped at 12 weeks.

    Reporting group title
    Treat and Extend
    Reporting group description
    		 Individualised Treat and Extend treatment regimen. Phase 1: Monthly treatments for 3 consecutive visits Phase 2: The treatment interval progressively extended by 2 weeks allowing a treatment interval to be found maintaining stability as per the investigators decision. Treatment interval capped at 12 weeks. Phase 3: If any relapse in activity or reactivation treatment interval progressively reduced by 2 weeks until stability is reached again. Phase 4: Further extension of the interval may be attempted following a fixed interval at the discretion of the the treating physician, capped to 12 weeks. Minimum shortened duration between doses of 4 weeks, maximum extension of intervals capped at 12 weeks.

    Serious adverse events
    		 Standard Care Treat and Extend
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 19 (47.37%)
    8 / 20 (40.00%)
         number of deaths (all causes)
    2
    2
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tongue neoplasm malignant stage unspecified
    Additional description: Toungue neoplasm malignant stage unspecified & carcinoma in situ of skin.
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Thermal burn
    Additional description: Fall and Thermal burn
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative thrombosis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Circulatory collapse
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 20 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures
    Additional description: Partial seizure and pneumonia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Eye haemorrhage
    Additional description: Led to vision loss >30 letters between visits defined as an SAE by Protocol
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (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
    Influenza
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia and sepsis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (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: 5%
    Non-serious adverse events
    		 Standard Care Treat and Extend
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    16 / 19 (84.21%)
    18 / 20 (90.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 20 (10.00%)
         occurrences all number
    1
    2
    Surgical and medical procedures
    Blepharoplasty
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Cataract operation
         subjects affected / exposed
    2 / 19 (10.53%)
    3 / 20 (15.00%)
         occurrences all number
    2
    3
    Office visit
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 20 (10.00%)
         occurrences all number
    0
    2
    Skin lesion removal
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Cold sweat, altered state of consciousness & vomiting
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Death
    Additional description: Death as a result of progression of pre-existing condition, not considered an SAE for the purposes of the study.
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Facial pain
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Fatigue
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Influenza like illness
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 20 (5.00%)
         occurrences all number
    1
    1
    Malaise & Dizziness
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    3
    Reproductive system and breast disorders
    Breast mass
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 20 (5.00%)
         occurrences all number
    1
    1
    Cough, nasopharyngitis & conjunctivitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Dyspnoea
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Epistaxis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Haemoptysis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Nasal congestion
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Weight decreased
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    7 / 19 (36.84%)
    4 / 20 (20.00%)
         occurrences all number
    7
    4
    Ligament sprain
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Atrial fibrillation
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Nervous system disorders
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Dizziness
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 20 (5.00%)
         occurrences all number
    3
    1
    Memory impairment
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Migraine
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 20 (5.00%)
         occurrences all number
    1
    2
    Eye disorders
    Age-related macular degeneration
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 20 (10.00%)
         occurrences all number
    0
    2
    Blepharitis
         subjects affected / exposed
    4 / 19 (21.05%)
    1 / 20 (5.00%)
         occurrences all number
    6
    1
    Cataract
         subjects affected / exposed
    0 / 19 (0.00%)
    3 / 20 (15.00%)
         occurrences all number
    0
    4
    Cataract nuclear
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Charles Bonnet syndrome
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Choroidal neovascularisation
         subjects affected / exposed
    3 / 19 (15.79%)
    1 / 20 (5.00%)
         occurrences all number
    3
    1
    Corneal abrasion
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 20 (0.00%)
         occurrences all number
    2
    0
    Diplopia
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 20 (5.00%)
         occurrences all number
    1
    1
    Dry eye
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 20 (5.00%)
         occurrences all number
    2
    1
    Eye inflammation
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Eye pain
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 20 (5.00%)
         occurrences all number
    1
    1
    Eyelid contusion
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Eyelid disorder
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Eyelid thickening
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Intraocular pressure increased
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 20 (10.00%)
         occurrences all number
    3
    2
    Iris transillumination defect
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Lens disorder
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Lenticular opacities
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Metamorphopsia
         subjects affected / exposed
    3 / 19 (15.79%)
    1 / 20 (5.00%)
         occurrences all number
    5
    2
    Neovascular age-related macular degeneration
         subjects affected / exposed
    0 / 19 (0.00%)
    4 / 20 (20.00%)
         occurrences all number
    0
    4
    Retinal haemorrhage
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Retinal oedema
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Retinal pigment epithelial tear
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 20 (5.00%)
         occurrences all number
    2
    1
    Sensation of foreign body
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Subretinal fibrosis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Vision blurred
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Visual acuity reduced
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Visual impairment
    Additional description: Patient reported perceived worsening of vision between study visits.
    alternative assessment type: Systematic
         subjects affected / exposed
    10 / 19 (52.63%)
    5 / 20 (25.00%)
         occurrences all number
    18
    10
    Visual impairment & metamorphosia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Visual impairment & Nuclear cataract
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Vitreoretinal traction syndrome
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Vitreous detachment
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 20 (5.00%)
         occurrences all number
    1
    1
    Vitreous floaters
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    2
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 20 (10.00%)
         occurrences all number
    1
    3
    Constipation
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Diarrhoea
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Diverticulitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Dyspepsia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Nausea
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Nausea & back pain
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Vomiting
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 20 (0.00%)
         occurrences all number
    3
    0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Decubitus ulcer
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Eczema
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Psoriasis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Rash
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Skin ulcer
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 20 (0.00%)
         occurrences all number
    3
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 20 (10.00%)
         occurrences all number
    0
    2
    Back pain
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Foot fracture
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Joint swelling
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Osteoarthritis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    2
    Pain in extremity
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Pain in jaw
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 20 (0.00%)
         occurrences all number
    2
    0
    Trigger finger
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Campylobacter gastroenteritis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Candida infection
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Cellulitis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Cystitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Fungal skin infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Herpes zoster
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 20 (5.00%)
         occurrences all number
    1
    1
    Hordeolum
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Influenza
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Lower respiratory tract infection
         subjects affected / exposed
    5 / 19 (26.32%)
    4 / 20 (20.00%)
         occurrences all number
    5
    9
    Nasopharyngitis & Influenza
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Postoperative wound infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Tooth infection
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 20 (10.00%)
         occurrences all number
    1
    2
    Urinary tract infection
         subjects affected / exposed
    0 / 19 (0.00%)
    3 / 20 (15.00%)
         occurrences all number
    0
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Jan 2016
    SA02 This amendment was submitted to allow screening and baseline/treatment to either be on the same day, Day 0, or over two days, within a seven day permitted window. This alteration allowed flexibility for patients as some may wish to stay longer and have their treatment on the same day; other patients may prefer to come back to clinic as the appointments can be quite long. Screening procedures were also clarified to enable Patient Information Sheets to be sent to patients at home. This would be done following initial consultation with the Doctor and only if it was not possible to provide one during their consultation. The PIS would only be sent out following confirmation with the Doctor that this was suitable. Randomisation and labelling procedures were also clarified.
    17 Mar 2016
    SA04 Addition of two new sites for recruitment
    24 Jul 2016
    SA06 This amendment was submitted to amend the parameters for the blood pressure exclusion criteria to 170mmHg and/or 110mmHg. This change was proposed as most patients had an element of white coat hypertension when they attended clinics, and the new values would assist in recruiting those with white coat hypertension rather than true hypertension. Furthermore, the QoL questionnaire was to be administrated following the first injection, as participants had commented the completion of this at baseline visit was confusing. Also amended within the protocol was a clarification of staff and the removal of the reference to the NEI-VFQ as this was not being measured.
    13 Jan 2017
    SA10 This amendment was submitted to amend Appendix 7 of the study protocol to state that interviews would be conducted with staff. A new Participant Information Sheet and consent form were included for review, along with a topic guide which detailed what would be asked.
    20 Oct 2017
    SA12 Update of SmPC containing RSI for the study to version 11 following review
    14 Feb 2018
    SA13, SA15 and NSA16. (multiple references for regulatory approvals) This amendment was submitted to address a number of points including: - An extension for a further two years - The addition of a ‘monitor and extend’ element in years 3 and 4 - Authorisation for Trusts to follow their standard injection practice - Addition of an SAE of special interest: Vision loss of >30 letters between visits.

    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.
    MATE was designed and run as a pilot study therefore the numbers aren't large enough to draw comparison between the arms. Covid-19 restrictions impacted on visit attendance between 36 and 48 months.
    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.

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