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    Clinical Trial Results:
    A Prospective, Randomized, Double-masked, Sham-controlled, Multi-center, Two-arm, Phase 3 Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 in Participants with Moderately Severe to Severe Non-proliferative Diabetic Retinopathy (NPDR)

    Summary
    EudraCT number
    		 2020-001064-29
    Trial protocol
    		 SK   ES   LV   CZ  
    Global end of trial date
    31 Aug 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    08 Sep 2024
    First version publication date
    08 Sep 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    KS301P106
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05066230
    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-106 Trial Information, Kodiak Sciences Inc., ksi301clinical@kodiak.com
    Scientific contact
    KSI-CL-106 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
    26 Sep 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    03 Aug 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Aug 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 superior to sham treatment, with respect to proportion of eyes improving ≥2 steps on Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 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
    30 Aug 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: 1
    Country: Number of subjects enrolled
    Slovakia: 2
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    Czechia: 1
    Country: Number of subjects enrolled
    United States: 243
    Worldwide total number of subjects
    253
    EEA total number of subjects
    10
    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)
    191
    From 65 to 84 years
    62
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants were recruited based on physician referral at 52 medical centers between September 2021 and August 2022. The first participant was enrolled on 07 September 2021 and the last on 25 August 2022.

    Pre-assignment
    Screening details
    		 Of 560 enrolled participants, 253 met eligibility criteria and were randomized to treatment.

    Period 1
    Period 1 title
    Primary Study (Through Week 48)
    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): three initiating doses, and then every 24 weeks through Week 92
    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
    		 Sham - Treatment Group B
    Arm description
    		 Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.
    Arm type
    		 Sham Comparator

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		KSI-301 - Treatment Group A Sham - Treatment Group B
    Started
    128
    125
    Completed
    120
    115
    Not completed
    8
    10
         Adverse event, serious fatal
    1
    1
         Consent withdrawn by subject
    4
    2
         Non-compliance with study schedule
    -
    1
         Adverse event, non-fatal
    -
    3
         Participant relocated
    1
    -
         Lost to follow-up
    2
    3
    Period 2
    Period 2 title
    After Week 48
    Is this the baseline period?
    		 No
    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): three initiating doses, and then every 24 weeks through Week 92 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
    		 Sham - Treatment Group B
    Arm description
    		 Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.
    Arm type
    		 Sham

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2
    		KSI-301 - Treatment Group A Sham - Treatment Group B
    Started
    120
    115
    Completed
    0
    0
    Not completed
    120
    115
         Adverse event, serious fatal
    1
    -
         Consent withdrawn by subject
    -
    1
         Non-compliance with study schedule
    1
    -
         Lost to follow-up
    3
    3
         Sponsor Request
    115
    111

    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): three initiating doses, and then every 24 weeks through Week 92

    Reporting group title
    Sham - Treatment Group B
    Reporting group description
    		 Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

    Reporting group values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B Total
    Number of subjects
    		 128 125 253
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 96 95 191
        From 65-84 years
    		 32 30 62
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 56.4 ( 11.39 ) 57.0 ( 9.63 ) -
    Gender categorical
    Units: Subjects
        Female
    		 51 56 107
        Male
    		 77 69 146
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 2 2
        Asian
    		 3 3 6
        Black or African American
    		 13 23 36
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        White
    		 108 96 204
        Multiple
    		 2 0 2
        Other
    		 2 1 3
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 57 52 109
        Not Hispanic or Latino
    		 71 73 144
    ETDRS Diabetic Retinopathy Severity Score at Baseline
    Units: Subjects
        DRSS Level <=47
    		 46 45 91
        DRSS Level >=53
    		 82 80 162

    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): three initiating doses, and then every 24 weeks through Week 92

    Reporting group title
    Sham - Treatment Group B
    Reporting group description
    		 Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.
    Reporting group title
    KSI-301 - Treatment Group A
    Reporting group description
    		 Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection

    Reporting group title
    Sham - Treatment Group B
    Reporting group description
    		 Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

    Subject analysis set title
    Primary Study
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment.

    Primary: Percentage of Patients Improving ≥2 Steps on DRSS

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    End point title
    		 Percentage of Patients Improving ≥2 Steps on DRSS
    End point description
    Percentage of patients improving ≥2 steps on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF)
    End point type
    Primary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128
    125
    Units: Participants
    52
    2
    Statistical analysis title
    		 Statistical Analysis 1 for Percentage of Patients
    Comparison groups
    KSI-301 - Treatment Group A v Sham - Treatment Group B
    Number of subjects included in analysis
    253
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [1]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference of weighted percentage
    Point estimate
    39.7
    Confidence interval
         level
    		 95.02%
         sides
    2-sided
         lower limit
    		 31.3
         upper limit
    		 48.1
    Notes
    [1] - Cochran-Mantel-Haentzel test stratified by baseline DRSS level (≤level 47 vs. ≥level 53) and HbA1c level (≤8.5% vs. >8.5%)

    Secondary: Percentage of Patients Developing Any Sight-Threatening Complication

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    End point title
    		 Percentage of Patients Developing Any Sight-Threatening Complication
    End point description
    Percentage of patients developing any of the following Sight-Threatening Complication: Proliferative Diabetic Retinopathy (PDR), Anterior segment neovascularization (ASNV), Vitreous hemorrhage or tractional retinal detachment believed to be due to PDR, or Diabetic Macular Edema (DME) from baseline through Week 48
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128
    125
    Units: Participants
    3
    26
    Statistical analysis title
    		 Statistical Analysis 1 for Percentage of Patients
    Comparison groups
    KSI-301 - Treatment Group A v Sham - Treatment Group B
    Number of subjects included in analysis
    253
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [2]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference of weighted percentage
    Point estimate
    -18.7
    Confidence interval
         level
    		 95.02%
         sides
    2-sided
         lower limit
    		 -26.2
         upper limit
    		 -11.2
    Notes
    [2] - Cochran-Mantel-Haentzel test stratified by baseline DRSS level (≤level 47 vs. ≥level 53) and HbA1c level (≤8.5% vs. >8.5%).

    Secondary: Percentage of Patients Improving ≥3 Steps on DRSS

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    End point title
    		 Percentage of Patients Improving ≥3 Steps on DRSS
    End point description
    Percentage of patients improving ≥3 steps on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF)
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128
    125
    Units: Participants
    7
    0
    Statistical analysis title
    		 Statistical Analysis 1 for Percentage of Patients
    Comparison groups
    KSI-301 - Treatment Group A v Sham - Treatment Group B
    Number of subjects included in analysis
    253
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0058 [3]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference of weighted percentage
    Point estimate
    5.6
    Confidence interval
         level
    		 95.02%
         sides
    2-sided
         lower limit
    		 1.6
         upper limit
    		 9.5
    Notes
    [3] - Cochran-Mantel-Haentzel test stratified by baseline DRSS level (≤level 47 vs. ≥level 53), HbA1c level (≤8.5% vs. >8.5%).

    Secondary: Percentage of Patients Developing PDR

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    End point title
    		 Percentage of Patients Developing PDR
    End point description
    Percentage of patients developing Proliferative Diabetic Retinopathy (PDR) from baseline through Week 48
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128
    125
    Units: Participants
    2
    10
    Statistical analysis title
    		 Statistical Analysis 1 for Percentage of Patients
    Comparison groups
    KSI-301 - Treatment Group A v Sham - Treatment Group B
    Number of subjects included in analysis
    253
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0149 [4]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference of weighted percentage
    Point estimate
    -6.5
    Confidence interval
         level
    		 95.02%
         sides
    2-sided
         lower limit
    		 -11.8
         upper limit
    		 -1.3
    Notes
    [4] - Cochran-Mantel-Haentzel test stratified by baseline DRSS level (≤level 47 vs. ≥level 53) and HbA1c level (≤8.5% vs. >8.5%).

    Secondary: Percentage of Patients Developing PDR or ASNV

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    End point title
    		 Percentage of Patients Developing PDR or ASNV
    End point description
    Percentage of patients developing Proliferative Diabetic Retinopathy (PDR) or Anterior segment neovascularization (ASNV) from baseline through Week 48
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128
    125
    Units: Participants
        Percentage of Patients Developing PDR or ASNV
    2
    10
    No statistical analyses for this end point

    Secondary: Percentage of Patients Developing Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR

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    End point title
    		 Percentage of Patients Developing Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR
    End point description
    Percentage of patients developing vitreous hemorrhage or tractional retinal detachment believed to be due to Proliferative Diabetic Retinopathy (PDR) from baseline through Week 48
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128
    125
    Units: Participants
    2
    3
    No statistical analyses for this end point

    Secondary: Percentage of patients developing DME

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    End point title
    		 Percentage of patients developing DME
    End point description
    Percentage of patients developing Diabetic Macular Edema (DME) from baseline through Week 48
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128
    125
    Units: Participants
    1
    17
    No statistical analyses for this end point

    Secondary: Percentage of Patients With a ≥2-step or ≥3-step Worsening on DRSS

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    End point title
    		 Percentage of Patients With a ≥2-step or ≥3-step Worsening on DRSS
    End point description
    Percentage of patients with a ≥2-step or ≥3-step worsening on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached).
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128
    125
    Units: Participants
    number (not applicable)
        Patients with a ≥2-step worsening on DRSS (n)
    1
    5
        Patients with a ≥2-step worsening on DRSS (%)
    0.78
    4
        Patients with a ≥3-step worsening on DRSS (n)
    0
    3
        Patients with a ≥3-step worsening on DRSS (%)
    0
    2.4
    No statistical analyses for this end point

    Secondary: Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA

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    End point title
    		 Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA
    End point description
    Percentage of patients who lost ≥5, ≥10, or ≥15 letters in Best-corrected Visual Acuity (BCVA) from baseline by visit over time
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128
    125
    Units: Participants
    number (not applicable)
        lost ≥ 5 letters from baseline-Wk 8 (N analysed)
    127
    123
        lost ≥ 5 letters from baseline-Wk 8 (n)
    8
    15
        lost ≥ 5 letters from baseline-Wk 8 (%)
    6.3
    12.2
        lost ≥ 5 letters from baseline-Wk 20 (N analysed)
    122
    109
        lost ≥ 5 letters from baseline-Wk 20 (n)
    15
    15
        lost ≥ 5 letters from baseline-Wk 20 (%)
    12.3
    13.76
        lost ≥ 5 letters from baseline-Wk 32 (N analysed)
    117
    99
        lost ≥ 5 letters from baseline-Wk 32 (n)
    17
    10
        lost ≥ 5 letters from baseline-Wk 32 (%)
    14.53
    10.1
        lost ≥ 5 letters from baseline-Wk 44 (N analysed)
    109
    90
        lost ≥ 5 letters from baseline-Wk 44 (n)
    12
    8
        lost ≥ 5 letters from baseline-Wk 44 (%)
    11.01
    8.89
        lost ≥ 5 letters from baseline-Wk 48 (N analysed)
    114
    91
        lost ≥ 5 letters from baseline-Wk 48 (n)
    14
    11
        lost ≥ 5 letters from baseline-Wk 48 (%)
    12.28
    12.09
        lost ≥10 letters from baseline-Wk 8 (N analysed)
    127
    123
        lost ≥10 letters from baseline-Wk 8 (n)
    2
    3
        lost ≥10 letters from baseline-Wk 8 (%)
    1.57
    2.44
        lost ≥10 letters from baseline-Wk 20 (N analysed)
    122
    109
        lost ≥10 letters from baseline-Wk 20 (n)
    2
    4
        lost ≥10 letters from baseline-Wk 20 (%)
    1.64
    3.67
        lost ≥10 letters from baseline-Wk 32 (N analysed)
    117
    99
        lost ≥10 letters from baseline-Wk 32 (n)
    5
    1
        lost ≥10 letters from baseline-Wk 32 (%)
    4.27
    1.01
        lost ≥10 letters from baseline-Wk 44 (N analysed)
    109
    90
        lost ≥10 letters from baseline-Wk 44 (n)
    4
    2
        lost ≥10 letters from baseline-Wk 44 (%)
    3.67
    2.22
        lost ≥10 letters from baseline-Wk 48 (N analysed)
    114
    91
        lost ≥10 letters from baseline-Wk 48 (n)
    5
    1
        lost ≥10 letters from baseline-Wk 48 (%)
    4.39
    1.1
        lost ≥15 letters from baseline-Wk 8 (N analysed)
    127
    123
        lost ≥15 letters from baseline-Wk 8 (n)
    1
    1
        lost ≥15 letters from baseline-Wk 8 (%)
    0.79
    0.81
        lost ≥15 letters from baseline-Wk 20 (N analysed)
    122
    109
        lost ≥15 letters from baseline-Wk 20 (n)
    1
    1
        lost ≥15 letters from baseline-Wk 20 (%)
    0.82
    0.92
        lost ≥15 letters from baseline-Wk 32 (N analysed)
    117
    99
        lost ≥15 letters from baseline-Wk 32 (n)
    4
    0
        lost ≥15 letters from baseline-Wk 32 (%)
    3.42
    0
        lost ≥15 letters from baseline-Wk 44 (N analysed)
    109
    90
        lost ≥15 letters from baseline-Wk 44 (n)
    0
    0
        lost ≥15 letters from baseline-Wk 44 (%)
    0
    0
        lost ≥15 letters from baseline-Wk 48 (N analysed)
    114
    91
        lost ≥15 letters from baseline-Wk 48 (n)
    3
    0
        lost ≥15 letters from baseline-Wk 48 (%)
    2.63
    0
    No statistical analyses for this end point

    Secondary: Time to First Levelopment of PDR, ASNV, or DME

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    End point title
    		 Time to First Levelopment of PDR, ASNV, or DME
    End point description
    Time to first development of Proliferative Diabetic Retinopathy (PDR), Anterior segment neovascularisation (ASNV), or Diabetic Macular Edema (DME) through Week 48
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128 [5]
    125 [6]
    Units: Months
    median (confidence interval 95%)
        Time to 1st development of PDR, ASNV or DME
    0 (0 to 0)
    0 (0 to 0)
    Notes
    [5] - 0 = Not available due to small number of PDR, ASNV and DME events
    [6] - 0 = Not available due to small number of PDR, ASNV and DME events
    No statistical analyses for this end point

    Secondary: Time to First Development of PDR or ASNV

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    End point title
    		 Time to First Development of PDR or ASNV
    End point description
    Time to first development of Proliferative Diabetic Retinopathy (PDR) or Anterior Segment Neovascularization (ASNV) through Week 48
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128 [7]
    125 [8]
    Units: Months
    median (confidence interval 95%)
        Time to first development of PDR or ASNV
    0 (0 to 0)
    0 (0 to 0)
    Notes
    [7] - 0 = Not available due to small number of PDR and ASNV events
    [8] - 0 = Not available due to small number of PDR and ASNV events
    No statistical analyses for this end point

    Secondary: Time to First Development of Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR

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    End point title
    		 Time to First Development of Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR
    End point description
    Time to first development of vitreous hemorrhage (VH) or tractional retinal detachment (TRD) believed to be due to Proliferative Diabetic Retinopathy (PDR) through Week 48
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128 [9]
    125 [10]
    Units: Months
    median (confidence interval 95%)
        Time to 1st development of VH or TRD
    0 (0 to 0)
    0 (0 to 0)
    Notes
    [9] - 0 = Not available due to small number of vitreous haemorrhage & tractional retinal detachment
    [10] - 0 = Not available due to small number of vitreous haemorrhage & tractional retinal detachment
    No statistical analyses for this end point

    Other pre-specified: Mean Change in OCT CST

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    End point title
    		 Mean Change in OCT CST
    End point description
    Mean change in Optical Coherence Tomography (OCT) central subfield retinal thickness (CST) from baseline by visit over time
    End point type
    Other pre-specified
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128
    125
    Units: Microns
    arithmetic mean (standard deviation)
        Week 8 (n = 127, 123)
    -9.8 ( 10.64 )
    4.5 ( 17.22 )
        Week 20 (n = 122, 109)
    -12.8 ( 13.42 )
    6.6 ( 28.99 )
        Week 32 (n = 117, 99)
    -13.9 ( 14.88 )
    5.2 ( 27.86 )
        Week 44 (n = 109, 90)
    -8.9 ( 19.71 )
    -0.5 ( 17.12 )
        Week 48 (n = 114, 91)
    -15.2 ( 16.35 )
    -0.7 ( 15.76 )
    No statistical analyses for this end point

    Other pre-specified: Mean Change in BCVA

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    End point title
    		 Mean Change in BCVA
    End point description
    Mean change in Best-corrected Visual Acuity (BCVA) from baseline by visit over time
    End point type
    Other pre-specified
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128
    125
    Units: ETDRS Letters
    arithmetic mean (standard deviation)
        Week 8 (n = 127, 123)
    1.3 ( 5.02 )
    0.2 ( 4.80 )
        Week 20 (n = 122, 109)
    1.1 ( 5.22 )
    0.3 ( 6.29 )
        Week 32 (n = 117, 99)
    0.9 ( 8.68 )
    1.2 ( 4.87 )
        Week 44 (n = 109, 90)
    1.0 ( 5.63 )
    1.6 ( 5.55 )
        Week 48 (n = 114, 91)
    1.1 ( 6.44 )
    1.5 ( 5.49 )
    No statistical analyses for this end point

    Other pre-specified: Time to First Development of DME

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    End point title
    		 Time to First Development of DME
    End point description
    Time to first development of Diabetic Macular Edema (DME) through Week 48
    End point type
    Other pre-specified
    End point timeframe
    Day 1 to Week 48
    End point values
    		 KSI-301 - Treatment Group A Sham - Treatment Group B
    Number of subjects analysed
    128 [11]
    125 [12]
    Units: Months
    median (confidence interval 95%)
        Time to first development of DME
    0 (0 to 0)
    0 (0 to 0)
    Notes
    [11] - 0 = Not available due to small number of DME events
    [12] - 0 = Not available due to small number of DME events
    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 the End of Study 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 (Day 1 to Week 48)
    Reporting group description
    		 Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection

    Reporting group title
    Treatment Group B (Day 1 to Week 48)
    Reporting group description
    		 Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

    Reporting group title
    KSI-301 - Treatment Group A (Post Week 48 to End of Study)
    Reporting group description
    		 Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 KSI-301: Intravitreal injection

    Reporting group title
    Treatment Group B (Post Week 48 to End of Study)
    Reporting group description
    		 Sham injection on the same schedule as Treatment Group A Sham injection: The sham injection 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 is performed to maintain masking of the study.

    Serious adverse events
    		 KSI-301 - Treatment Group A (Day 1 to Week 48) Treatment Group B (Day 1 to Week 48) KSI-301 - Treatment Group A (Post Week 48 to End of Study) Treatment Group B (Post Week 48 to End of Study)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    18 / 128 (14.06%)
    12 / 125 (9.60%)
    8 / 120 (6.67%)
    3 / 115 (2.61%)
         number of deaths (all causes)
    1
    1
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Vascular disorders
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    0 / 128 (0.00%)
    1 / 125 (0.80%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    2 / 120 (1.67%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonia aspiration
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 128 (0.00%)
    0 / 125 (0.00%)
    1 / 120 (0.83%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Alcohol poisoning
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periprosthetic fracture
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 128 (0.00%)
    0 / 125 (0.00%)
    1 / 120 (0.83%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 128 (0.00%)
    0 / 125 (0.00%)
    1 / 120 (0.83%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Coronary artery disease
         subjects affected / exposed
    2 / 128 (1.56%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulseless electrical activity
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 128 (0.00%)
    1 / 125 (0.80%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ischaemic stroke
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral arteriosclerosis
         subjects affected / exposed
    0 / 128 (0.00%)
    1 / 125 (0.80%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 128 (0.00%)
    1 / 125 (0.80%)
    0 / 120 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    0 / 128 (0.00%)
    1 / 125 (0.80%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal vein occlusion - Fellow Eye
         subjects affected / exposed
    0 / 128 (0.00%)
    1 / 125 (0.80%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 128 (0.00%)
    1 / 125 (0.80%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 128 (0.00%)
    1 / 125 (0.80%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Gallbladder rupture
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Portal vein thrombosis
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    0 / 128 (0.00%)
    1 / 125 (0.80%)
    1 / 120 (0.83%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    0 / 128 (0.00%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 128 (0.00%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Localised infection
         subjects affected / exposed
    2 / 128 (1.56%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 128 (0.78%)
    2 / 125 (1.60%)
    2 / 120 (1.67%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Complicated appendicitis
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infected cyst
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 128 (0.00%)
    1 / 125 (0.80%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis staphylococcal
         subjects affected / exposed
    0 / 128 (0.00%)
    1 / 125 (0.80%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mycoplasma infection
         subjects affected / exposed
    0 / 128 (0.00%)
    1 / 125 (0.80%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 128 (0.00%)
    1 / 125 (0.80%)
    0 / 120 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis acute
         subjects affected / exposed
    0 / 128 (0.00%)
    0 / 125 (0.00%)
    1 / 120 (0.83%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 128 (0.00%)
    0 / 125 (0.00%)
    1 / 120 (0.83%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 128 (0.78%)
    0 / 125 (0.00%)
    1 / 120 (0.83%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 KSI-301 - Treatment Group A (Day 1 to Week 48) Treatment Group B (Day 1 to Week 48) KSI-301 - Treatment Group A (Post Week 48 to End of Study) Treatment Group B (Post Week 48 to End of Study)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    49 / 128 (38.28%)
    51 / 125 (40.80%)
    15 / 120 (12.50%)
    9 / 115 (7.83%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    12 / 128 (9.38%)
    10 / 125 (8.00%)
    2 / 120 (1.67%)
    1 / 115 (0.87%)
         occurrences all number
    13
    10
    2
    1
    Eye disorders
    Cataract - Study Eye
         subjects affected / exposed
    13 / 128 (10.16%)
    5 / 125 (4.00%)
    3 / 120 (2.50%)
    0 / 115 (0.00%)
         occurrences all number
    14
    5
    3
    0
    Conjunctival haemorrhage - Study Eye
         subjects affected / exposed
    9 / 128 (7.03%)
    4 / 125 (3.20%)
    1 / 120 (0.83%)
    0 / 115 (0.00%)
         occurrences all number
    9
    5
    1
    0
    Cataract - Fellow Eye
         subjects affected / exposed
    7 / 128 (5.47%)
    3 / 125 (2.40%)
    1 / 120 (0.83%)
    0 / 115 (0.00%)
         occurrences all number
    7
    3
    1
    0
    Diabetic retinal oedema - Study Eye
         subjects affected / exposed
    2 / 128 (1.56%)
    18 / 125 (14.40%)
    3 / 120 (2.50%)
    3 / 115 (2.61%)
         occurrences all number
    2
    19
    3
    3
    Diabetic retinopathy - Study Eye
         subjects affected / exposed
    2 / 128 (1.56%)
    8 / 125 (6.40%)
    1 / 120 (0.83%)
    3 / 115 (2.61%)
         occurrences all number
    2
    8
    1
    3
    Infections and infestations
    COVID-19
         subjects affected / exposed
    9 / 128 (7.03%)
    6 / 125 (4.80%)
    1 / 120 (0.83%)
    0 / 115 (0.00%)
         occurrences all number
    9
    7
    1
    0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    15 / 128 (11.72%)
    8 / 125 (6.40%)
    3 / 120 (2.50%)
    2 / 115 (1.74%)
         occurrences all number
    15
    8
    3
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 May 2021
    Version 1.1 - Changes from Version 1.0 (original protocol) include: minor editorial and administrative revisions.

    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.
    This study was terminated after all participants completed Wk 48 safety follow-up due to demonstration of efficacy at the Week 48 Primary Analysis. Results were not reported for some endpoints due to insufficient sample size.
    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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