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    Clinical Trial Results:
    A Prospective, Randomized, Double-masked, Active Comparator-controlled, Multi-center, Two-arm, Phase 3 Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 Compared with Intravitreal Aflibercept in Participants with Neovascular (Wet) Age-related Macular Degeneration (wAMD)

    Summary
    EudraCT number
    		 2021-000225-27
    Trial protocol
    		 ES   HU   LV   SK  
    Global end of trial date
    06 Apr 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Jul 2024
    First version publication date
    12 Jul 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    KS301P107
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04964089
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Kodiak Sciences Inc.
    Sponsor organisation address
    1200 Page Mill Road, Palo Alto, CA, United States, 94304
    Public contact
    KSI-CL-107 Trial Information , Kodiak Sciences Inc., ksi301clinical@kodiak.com
    Scientific contact
    KSI-CL-107 Trial Information , Kodiak Sciences Inc., ksi301clinical@kodiak.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
    17 May 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Mar 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Apr 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate that KSI-301 5 mg is non-inferior to aflibercept 2 mg, with respect to the change in best corrected visual acuity (BCVA) from Day 1 to the average of Weeks 40, 44 and 48.
    Protection of trial subjects
    The study followed the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All local regulatory requirements pertinent to safety of trial subjects were followed during the conduct of the trial. At the Investigator's discretion, treatment with pan-retinal photocoagulation laser.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 Jun 2021
    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
    Poland: 39
    Country: Number of subjects enrolled
    Slovakia: 2
    Country: Number of subjects enrolled
    Spain: 20
    Country: Number of subjects enrolled
    Czechia: 2
    Country: Number of subjects enrolled
    Hungary: 19
    Country: Number of subjects enrolled
    Latvia: 22
    Country: Number of subjects enrolled
    United States: 453
    Worldwide total number of subjects
    557
    EEA total number of subjects
    104
    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)
    37
    From 65 to 84 years
    421
    85 years and over
    99

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were recruited from 94 sites in 7 countries

    Pre-assignment
    Screening details
    		 The study comprised a screening period of 21 days

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 KSI-301 (Treatment Group A)
    Arm description
    		 Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tarcocimab tedromer
    Investigational medicinal product code
    KSI-301
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    5 mg via intravitreal injection

    Arm title
    		 Aflibercept (Treatment Group B)
    Arm description
    		 Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Aflibercept
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    2 mg via intravitreal injection

    Number of subjects in period 1
    		KSI-301 (Treatment Group A) Aflibercept (Treatment Group B)
    Started
    276
    281
    Completed
    254
    267
    Not completed
    22
    14
         Adverse event, serious fatal
    4
    3
         Participant moved to different state
    1
    -
         Consent withdrawn by subject
    7
    6
         Physician decision
    1
    -
         Non-compliance with study schedule
    1
    -
         Adverse event, non-fatal
    3
    3
         Lost to follow-up
    2
    2
         Progressive disease
    3
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    KSI-301 (Treatment Group A)
    Reporting group description
    		 Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection

    Reporting group title
    Aflibercept (Treatment Group B)
    Reporting group description
    		 Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.

    Reporting group values
    		 KSI-301 (Treatment Group A) Aflibercept (Treatment Group B) Total
    Number of subjects
    		 276 281 557
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 19 18 37
        From 65-84 years
    		 209 212 421
        85 years and over
    		 48 51 99
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 76.9 ( 8.21 ) 77.2 ( 7.84 ) -
    Gender categorical
    Units: Subjects
        Female
    		 159 180 339
        Male
    		 117 101 218
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 1 1
        Asian
    		 2 1 3
        Black or African American
    		 2 0 2
        Native Hawaiian or Other Pacific Islander
    		 0 2 2
        White
    		 269 276 545
        Multiple
    		 3 0 3
        Other
    		 0 1 1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 16 14 30
        Not Hispanic or Latino
    		 260 267 527
        Unknown or Not Reported
    		 0 0 0
    Subject analysis sets

    Subject analysis set title
    Full Analysis Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Full analysis set defined as all randomized subjects who received at least one treatment injection. Subjects will be analyzed according to their randomized treatment

    Subject analysis sets values
    		 Full Analysis Set
    Number of subjects
    557
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    37
        From 65-84 years
    421
        85 years and over
    99
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    77 ( 8.02 )
    Gender categorical
    Units: Subjects
        Female
    339
        Male
    218
    Race
    Units: Subjects
        American Indian or Alaska Native
    1
        Asian
    3
        Black or African American
    2
        Native Hawaiian or Other Pacific Islander
    2
        White
    545
        Multiple
    3
        Other
    1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    30
        Not Hispanic or Latino
    527
        Unknown or Not Reported
    0

    End points

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    End points reporting groups
    Reporting group title
    KSI-301 (Treatment Group A)
    Reporting group description
    		 Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection

    Reporting group title
    Aflibercept (Treatment Group B)
    Reporting group description
    		 Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.

    Subject analysis set title
    Full Analysis Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Full analysis set defined as all randomized subjects who received at least one treatment injection. Subjects will be analyzed according to their randomized treatment

    Primary: Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to the Average of Non-missing BCVA Values of Weeks 40, 44 and 48

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    End point title
    		 Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to the Average of Non-missing BCVA Values of Weeks 40, 44 and 48
    End point description
    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.
    End point type
    Primary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 (Treatment Group A) Aflibercept (Treatment Group B)
    Number of subjects analysed
    276
    281
    Units: ETDRS Letters
        least squares mean (standard error)
    2.5 ( 0.78 )
    4.6 ( 0.76 )
    Statistical analysis title
    		 Change in BCVA from baseline to avg of W40,W44,W48
    Comparison groups
    KSI-301 (Treatment Group A) v Aflibercept (Treatment Group B)
    Number of subjects included in analysis
    557
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    P-value
    		 = 0.0083 [2]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.1
    Confidence interval
         level
    		 95.03%
         sides
    2-sided
         lower limit
    		 -3.88
         upper limit
    		 -0.29
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.91
    Notes
    [1] - The maximum clinically acceptable true difference between KSI-301 and aflibercept participants to be considered non-inferior is 4.5 ETDRS letters, i.e. the non-inferiority margin (NI) is 4.5 letters.
    [2] - MMRM model with treatment, visit, treatment by visit interaction, randomization stratification factors, and continuous baseline BCVA as covariates.

    Secondary: Mean Change in BCVA by Visit Over Time

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    End point title
    		 Mean Change in BCVA by Visit Over Time
    End point description
    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 (Treatment Group A) Aflibercept (Treatment Group B)
    Number of subjects analysed
    276
    281
    Units: ETDRS Letters
    arithmetic mean (standard deviation)
        Week 2 (n=270,275)
    2.8 ( 6.48 )
    2.9 ( 7.12 )
        Week 4 (n=273,278)
    3.4 ( 7.05 )
    4.2 ( 7.29 )
        Week 8 (n=274,274)
    3.7 ( 8.52 )
    5.1 ( 7.86 )
        Week 12 (n=267,274)
    3.8 ( 8.83 )
    5.4 ( 7.90 )
        Week 16 (n=264,274)
    3.6 ( 9.09 )
    4.9 ( 8.54 )
        Week 20 (n=262,275)
    3.9 ( 9.6 )
    5.7 ( 8.97 )
        Week 24 (n=261,270)
    4.5 ( 9.29 )
    6.0 ( 9.45 )
        Week 28 (n=257,263)
    4.5 ( 9.75 )
    6.1 ( 9.49 )
        Week 32 (n=252,268)
    3.9 ( 10.32 )
    6.1 ( 9.86 )
        Week 36 (n=250,266)
    3.7 ( 10.58 )
    6.1 ( 9.77 )
        Week 40 (n=246,265)
    4.0 ( 11.05 )
    5.6 ( 10.75 )
        Week 44 (n=240,260)
    4.7 ( 9.99 )
    5.9 ( 10.71 )
        Week 48 (n=245,262)
    3.7 ( 11.12 )
    5.4 ( 11.36 )
    No statistical analyses for this end point

    Secondary: Proportion of Participants Who Gained ≥ 5, ≥10, and ≥15 Letters from Baseline Over Time

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    End point title
    		 Proportion of Participants Who Gained ≥ 5, ≥10, and ≥15 Letters from Baseline Over Time
    End point description
    Categorical improvements in Best Corrected Visual Acuity (BCVA) of clinically relevant BCVA measurements corresponding to 1, 2 and 3 lines of the ETDRS vision testing chart
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 (Treatment Group A) Aflibercept (Treatment Group B)
    Number of subjects analysed
    276
    281
    Units: Participants
        Gain ≥5 ETDRS Letters, Week 2 (n=270,275)
    100
    96
        Gain ≥5 ETDRS Letters, Week 4 (n=273,278)
    110
    129
        Gain ≥5 ETDRS Letters, Week 8 (n=274,274)
    119
    151
        Gain ≥5 ETDRS Letters, Week 12 (n=267,274)
    124
    148
        Gain ≥5 ETDRS Letters, Week 16 (n=264,274)
    119
    143
        Gain ≥5 ETDRS Letters, Week 20 (n=262,275)
    121
    161
        Gain ≥5 ETDRS Letters, Week 24 (n=261,270)
    130
    156
        Gain ≥5 ETDRS Letters, Week 28 (n=257,263)
    122
    154
        Gain ≥5 ETDRS Letters, Week 32 (n=252,268)
    132
    168
        Gain ≥5 ETDRS Letters, Week 36 (n=250,266)
    120
    158
        Gain ≥5 ETDRS Letters, Week 40 (n=246,265)
    116
    156
        Gain ≥5 ETDRS Letters, Week 44 (n=240,260)
    126
    151
        Gain ≥5 ETDRS Letters, Week 48 (n=245,262)
    111
    150
        Gain ≥10 ETDRS Letters, Week 2 (n=270,275)
    31
    37
        Gain ≥10 ETDRS Letters, Week 4 (n=273,278)
    44
    54
        Gain ≥10 ETDRS Letters, Week 8 (n=274,274)
    52
    72
        Gain ≥10 ETDRS Letters, Week 12 (n=267,274)
    55
    72
        Gain ≥10 ETDRS Letters, Week 16 (n=264,274)
    62
    68
        Gain ≥10 ETDRS Letters, Week 20 (n=262,275)
    66
    86
        Gain ≥10 ETDRS Letters, Week 24 (n=261,270)
    70
    90
        Gain ≥10 ETDRS Letters, Week 28 (n=257,263)
    66
    87
        Gain ≥10 ETDRS Letters, Week 32 (n=252,268)
    57
    95
        Gain ≥10 ETDRS Letters, Week 36 (n=250,266)
    66
    81
        Gain ≥10 ETDRS Letters, Week 40 (n=246,265)
    67
    80
        Gain ≥10 ETDRS Letters, Week 44 (n=240,260)
    67
    86
        Gain ≥10 ETDRS Letters, Week 48 (n=245,262)
    65
    85
        Gain ≥15 ETDRS Letters, Week 2 (n=270,275)
    12
    11
        Gain ≥15 ETDRS Letters, Week 4 (n=273,278)
    18
    21
        Gain ≥15 ETDRS Letters, Week 8 (n=274,274)
    24
    28
        Gain ≥15 ETDRS Letters, Week 12 (n=267,274)
    20
    29
        Gain ≥15 ETDRS Letters, Week 16 (n=264,274)
    24
    33
        Gain ≥15 ETDRS Letters, Week 20 (n=262,275)
    28
    33
        Gain ≥15 ETDRS Letters, Week 24 (n=261,270)
    33
    42
        Gain ≥15 ETDRS Letters, Week 28 (n=257,263)
    36
    46
        Gain ≥15 ETDRS Letters, Week 32 (n=252,268)
    32
    37
        Gain ≥15 ETDRS Letters, Week 36 (n=250,266)
    32
    44
        Gain ≥15 ETDRS Letters, Week 40 (n=246,265)
    33
    45
        Gain ≥15 ETDRS Letters, Week 44 (n=240,260)
    34
    48
        Gain ≥15 ETDRS Letters, Week 48 (n=245,262)
    35
    49
    No statistical analyses for this end point

    Secondary: Proportion of Participants Who Lost ≥5, ≥10, and ≥15 Letters from Baseline Over Time

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    End point title
    		 Proportion of Participants Who Lost ≥5, ≥10, and ≥15 Letters from Baseline Over Time
    End point description
    Categorical worsening in Best Corrected Visual Acuity (BCVA) of clinically relevant BCVA measurements corresponding to 1, 2 and 3 lines of the ETDRS vision testing chart
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 (Treatment Group A) Aflibercept (Treatment Group B)
    Number of subjects analysed
    276
    281
    Units: Participants
        Loss ≥5 ETDRS Letters, Week 2 (n=270,275)
    20
    28
        Loss ≥5 ETDRS Letters, Week 4 (n=273,278)
    27
    19
        Loss ≥5 ETDRS Letters, Week 8 (n=274,274)
    41
    22
        Loss ≥5 ETDRS Letters, Week 12 (n=267,274)
    35
    24
        Loss ≥5 ETDRS Letters, Week 16 (n=264,274)
    35
    31
        Loss ≥5 ETDRS Letters, Week 20 (n=262,275)
    35
    27
        Loss ≥5 ETDRS Letters, Week 24 (n=261,270)
    34
    31
        Loss ≥5 ETDRS Letters, Week 28 (n=257,263)
    38
    31
        Loss ≥5 ETDRS Letters, Week 32 (n=252,268)
    41
    35
        Loss ≥5 ETDRS Letters, Week 36 (n=250,266)
    47
    32
        Loss ≥5 ETDRS Letters, Week 40 (n=246,265)
    33
    41
        Loss ≥5 ETDRS Letters, Week 44 (n=240,260)
    33
    33
        Loss ≥5 ETDRS Letters, Week 48 (n=245,262)
    39
    38
        Loss ≥10 ETDRS Letters, Week 2 (n=270,275)
    6
    10
        Loss ≥10 ETDRS Letters, Week 4 (n=273,278)
    6
    4
        Loss ≥10 ETDRS Letters, Week 8 (n=274,274)
    10
    8
        Loss ≥10 ETDRS Letters, Week 12 (n=267,274)
    15
    9
        Loss ≥10 ETDRS Letters, Week 16 (n=264,274)
    15
    15
        Loss ≥10 ETDRS Letters, Week 20 (n=262,275)
    16
    14
        Loss ≥10 ETDRS Letters, Week 24 (n=261,270)
    17
    12
        Loss ≥10 ETDRS Letters, Week 28 (n=257,263)
    21
    14
        Loss ≥10 ETDRS Letters, Week 32 (n=252,268)
    23
    16
        Loss ≥10 ETDRS Letters, Week 36 (n=250,266)
    22
    18
        Loss ≥10 ETDRS Letters, Week 40 (n=246,265)
    21
    24
        Loss ≥10 ETDRS Letters, Week 44 (n=240,260)
    18
    21
        Loss ≥10 ETDRS Letters, Week 48 (n=245,262)
    24
    25
        Loss ≥15 ETDRS Letters, Week 2 (n=270,275)
    3
    4
        Loss ≥15 ETDRS Letters, Week 4 (n=273,278)
    4
    4
        Loss ≥15 ETDRS Letters, Week 8 (n=274,274)
    4
    4
        Loss ≥15 ETDRS Letters, Week 12 (n=267,274)
    6
    3
        Loss ≥15 ETDRS Letters, Week 16 (n=264,274)
    9
    5
        Loss ≥15 ETDRS Letters, Week 20 (n=262,275)
    7
    6
        Loss ≥15 ETDRS Letters, Week 24 (n=261,270)
    7
    6
        Loss ≥15 ETDRS Letters, Week 28 (n=257,263)
    7
    5
        Loss ≥15 ETDRS Letters, Week 32 (n=252,268)
    10
    9
        Loss ≥15 ETDRS Letters, Week 36 (n=250,266)
    14
    9
        Loss ≥15 ETDRS Letters, Week 40 (n=246,265)
    18
    13
        Loss ≥15 ETDRS Letters, Week 44 (n=240,260)
    8
    11
        Loss ≥15 ETDRS Letters, Week 48 (n=245,262)
    15
    13
    No statistical analyses for this end point

    Secondary: Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters)

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    End point title
    		 Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters)
    End point description
    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 (Treatment Group A) Aflibercept (Treatment Group B)
    Number of subjects analysed
    276
    281
    Units: Participants
        Baseline (n=276,281)
    122
    129
        Week 2 (n=270,275)
    148
    152
        Week 4 (n=273,278)
    156
    165
        Week 8 (n=274,274)
    156
    165
        Week 12 (n=267,274)
    148
    171
        Week 16 (n=264,274)
    149
    172
        Week 20 (n=262,275)
    151
    179
        Week 24 (n=261,270)
    158
    183
        Week 28 (n=257,263)
    151
    175
        Week 32 (n=252,268)
    147
    174
        Week 36 (n=250,266)
    147
    179
        Week 40 (n=246,265)
    151
    174
        Week 44 (n=240,260)
    149
    178
        Week 48 (n=245,262)
    144
    175
    No statistical analyses for this end point

    Secondary: Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters)

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    End point title
    		 Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters)
    End point description
    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 (Treatment Group A) Aflibercept (Treatment Group B)
    Number of subjects analysed
    276
    281
    Units: Participants
        Baseline (n=276,281)
    17
    15
        Week 2 (n=270,275)
    11
    12
        Week 4 (n=273,278)
    10
    14
        Week 8 (n=274,274)
    11
    13
        Week 12 (n=267,274)
    11
    12
        Week 16 (n=264,274)
    11
    10
        Week 20 (n=262,275)
    13
    13
        Week 24 (n=261,270)
    11
    13
        Week 28 (n=257,263)
    12
    13
        Week 32 (n=252,268)
    14
    18
        Week 36 (n=250,266)
    14
    13
        Week 40 (n=246,265)
    14
    17
        Week 44 (n=240,260)
    9
    15
        Week 48 (n=245,262)
    15
    15
    No statistical analyses for this end point

    Secondary: Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time

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    End point title
    		 Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time
    End point description
    Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) as assessed by a central reading center.
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 (Treatment Group A) Aflibercept (Treatment Group B)
    Number of subjects analysed
    276
    281
    Units: microns
    arithmetic mean (standard deviation)
        Week 2 (n=270,274)
    -72.1 ( 83.74 )
    -99.9 ( 93.75 )
        Week 4 (n=272,277)
    -74.9 ( 98.33 )
    -109.4 ( 100.87 )
        Week 8 (n=274,274)
    -89.1 ( 121.13 )
    -122.2 ( 109.58 )
        Week 12 (n=267,274)
    -97.1 ( 118.62 )
    -126.3 ( 111.5 )
        Week 16 (n=266,274)
    -107.2 ( 110.02 )
    -99.2 ( 110.47 )
        Week 20 (n=261,275)
    -111 ( 112.97 )
    -125.5 ( 117.39 )
        Week 24 (n=262,270)
    -109.9 ( 112.82 )
    -101.8 ( 113.21 )
        Week 28 (n=257,262)
    -114.6 ( 111.47 )
    -124.1 ( 111.51 )
        Week 32 (n=251,268)
    -111.9 ( 122.05 )
    -104.3 ( 116.09 )
        Week 36 (n=250,265)
    -113.6 ( 129.84 )
    -124.4 ( 112.12 )
        Week 40 (n=246,265)
    -113.6 ( 115.34 )
    -103.1 ( 109.25 )
        Week 44 (n=240,261)
    -115.8 ( 115.81 )
    -129.4 ( 114.70 )
        Week 48 (n=245,262)
    -117 ( 114 )
    -109.2 ( 120.75 )
        Week 40-48 Average (n=253,268)
    -114.6 ( 113.92 )
    -113.4 ( 112.07 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events (AEs) reported through Week 52 or Early Termination (ET)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    KSI-301 (Treatment Group A)
    Reporting group description
    		 Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. KSI-301: Intravitreal Injection

    Reporting group title
    Aflibercept (Treatment Group B)
    Reporting group description
    		 Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. Aflibercept: Intravitreal Injection Sham Procedure: The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.

    Serious adverse events
    		 KSI-301 (Treatment Group A) Aflibercept (Treatment Group B)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    39 / 276 (14.13%)
    39 / 281 (13.88%)
         number of deaths (all causes)
    4
    3
         number of deaths resulting from adverse events
    4
    2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung neoplasm malignant
         subjects affected / exposed
    2 / 276 (0.72%)
    2 / 281 (0.71%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cancer metastatic
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung neoplasm
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin cancer
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tongue neoplasm malignant stage unspecified
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 276 (0.00%)
    2 / 281 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 276 (0.72%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Infusion site extravasation
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    3 / 276 (1.09%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 276 (0.36%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 276 (0.72%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Intraocular pressure increased - Study Eye
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Hip fracture
         subjects affected / exposed
    1 / 276 (0.36%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extradural haematoma
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 276 (0.00%)
    2 / 281 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Accidental overdose
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acetabulum fracture
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foreign body
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomal hernia
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    2 / 276 (0.72%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 276 (0.36%)
    3 / 281 (1.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 276 (0.36%)
    2 / 281 (0.71%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 276 (0.36%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    1 / 276 (0.36%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Mitral valve incompetence
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    1 / 276 (0.36%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paralysis
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraparesis
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyskinesia
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Blood loss anaemia
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 276 (0.00%)
    4 / 281 (1.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment - Study Eye
         subjects affected / exposed
    3 / 276 (1.09%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye pain - Study Eye
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uveitis - Study Eye
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastric ulcer
         subjects affected / exposed
    1 / 276 (0.36%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal haemorrhage
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mesenteric vein thrombosis
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis necrotising
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (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 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         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 / 276 (0.36%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephritis
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal injury
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 276 (0.72%)
    3 / 281 (1.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    2 / 276 (0.72%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    2 / 276 (0.72%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 276 (0.72%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periorbital cellulitis - Study Eye
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 276 (0.36%)
    0 / 281 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 276 (0.00%)
    1 / 281 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 KSI-301 (Treatment Group A) Aflibercept (Treatment Group B)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    110 / 276 (39.86%)
    80 / 281 (28.47%)
    Investigations
    Intraocular pressure increased - Study Eye
         subjects affected / exposed
    15 / 276 (5.43%)
    2 / 281 (0.71%)
         occurrences all number
    17
    2
    Vascular disorders
    Hypertension
         subjects affected / exposed
    17 / 276 (6.16%)
    14 / 281 (4.98%)
         occurrences all number
    17
    14
    Eye disorders
    Neovascular age-related macular degeneration - Fellow Eye
         subjects affected / exposed
    22 / 276 (7.97%)
    15 / 281 (5.34%)
         occurrences all number
    23
    16
    Vitreous floaters - Study Eye
         subjects affected / exposed
    21 / 276 (7.61%)
    7 / 281 (2.49%)
         occurrences all number
    23
    7
    Conjunctival haemorrhage - Study Eye
         subjects affected / exposed
    20 / 276 (7.25%)
    11 / 281 (3.91%)
         occurrences all number
    26
    17
    Infections and infestations
    COVID-19
         subjects affected / exposed
    34 / 276 (12.32%)
    35 / 281 (12.46%)
         occurrences all number
    35
    35
    Urinary tract infection
         subjects affected / exposed
    15 / 276 (5.43%)
    16 / 281 (5.69%)
         occurrences all number
    23
    21

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Mar 2022
    Version 2.0 Major changes include extension of study by 8 weeks per patient, with addition of two additional study treatment visits at weeks 40 and 44; and change in primary efficacy endpoint timing from week 40 to average of weeks 40, 44, and 48.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None specified
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    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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