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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 Visual Impairment Secondary to Treatment-naïve Diabetic Macular Edema (DME).

    Summary
    EudraCT number
    2020-001062-11
    Trial protocol
    DE   LV   SK   HU   IT  
    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

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    Trial identification
    Sponsor protocol code
    KS301P104
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT04611152
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    IND Number: 136167
    Sponsors
    Sponsor organisation name
    Kodiak Sciences Inc.
    Sponsor organisation address
    1200 Page Mill Road, Palo Alto, CA, United States, 94304
    Public contact
    KSI301P104 Trial Information, Kodiak Sciences Inc., ksi301clinical@kodiak.com
    Scientific contact
    KSI301P104 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
    22 Sep 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 May 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Aug 2023
    Was the trial ended prematurely?
    Yes
    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 mean change in best corrected visual acuity (BCVA) from Day 1 to Year 1 (average of Weeks 48 and 52).
    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
    09 Sep 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 353
    Country: Number of subjects enrolled
    Slovakia: 25
    Country: Number of subjects enrolled
    Spain: 34
    Country: Number of subjects enrolled
    Germany: 10
    Country: Number of subjects enrolled
    Hungary: 11
    Country: Number of subjects enrolled
    Italy: 9
    Country: Number of subjects enrolled
    Latvia: 18
    Worldwide total number of subjects
    460
    EEA total number of subjects
    107
    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)
    274
    From 65 to 84 years
    183
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    Participants were recruited based on physician referral at 75 medical centers between September 2020 and February 2022. The first participant was enrolled on 30 September 2020 and the last on 16 February 2022.

    Pre-assignment
    Screening details
    Of 670 screened participants, 460 met eligibility criteria and were randomized to treatment.

    Period 1
    Period 1 title
    Primary Study Period (Day 1 to Week 64) (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Data analyst, Assessor
    Blinding implementation details
    Masking For masking purposes, sham injections will be administered at every monthly visit if an active treatment is not administered. To preserve masking, two investigators are required for this study. The masked Investigator will be responsible for the examinations and safety assessments. The unmasked Investigator will perform the injections and post-treatment assessments.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    KSI-301 (Arm A)
    Arm description
    Drug: 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
    Intravitreal injection of KSI-301 (5 mg) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100.

    Arm title
    Aflibercept (Arm B)
    Arm description
    Aflibercept: Intravitreal Injection
    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
    Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 5 monthly doses followed by aflibercept (2 mg) once every 8 weeks via intravitreal injection from Week 24 to 100.

    Number of subjects in period 1
    KSI-301 (Arm A) Aflibercept (Arm B)
    Started
    230
    230
    Completed
    205
    212
    Not completed
    25
    18
         Adverse event, serious fatal
    5
    5
         Consent withdrawn by subject
    5
    6
         Adverse event, non-fatal
    3
    2
         Lost to follow-up
    11
    2
         Non-compliance with Study Schedule
    1
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    KSI-301 (Arm A)
    Reporting group description
    Drug: KSI-301 Intravitreal Injection

    Reporting group title
    Aflibercept (Arm B)
    Reporting group description
    Aflibercept: Intravitreal Injection

    Reporting group values
    KSI-301 (Arm A) Aflibercept (Arm B) Total
    Number of subjects
    230 230 460
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    138 136 274
        From 65-84 years
    91 92 183
        85 years and over
    1 2 3
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    62 ( 9.73 ) 61.2 ( 10.61 ) -
    Gender categorical
    Units: Subjects
        Female
    80 87 167
        Male
    150 143 293
    Race
    Units: Subjects
        White
    204 200 404
        Black or African American
    21 21 42
        Asian
    3 3 6
        American Indian or Alaska Native
    1 1 2
        Native Hawaiian or Other Pacific Islander
    0 1 1
        Other
    1 4 5
        Multiple
    0 0 0
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    37 32 69
        Not Hispanic or Latino
    193 198 391
    BCVA in the Study Eye, Letter
    Units: Letters
        arithmetic mean (standard deviation)
    66.4 ( 9.78 ) 66.6 ( 9.60 ) -

    End points

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    End points reporting groups
    Reporting group title
    KSI-301 (Arm A)
    Reporting group description
    Drug: KSI-301 Intravitreal Injection

    Reporting group title
    Aflibercept (Arm B)
    Reporting group description
    Aflibercept: Intravitreal Injection

    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 any study treatment (KSI-301 or aflibercept). Subjects will be analyzed according to their randomized treatment.

    Primary: 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 to the average of Weeks 60 and 64 (using Early Treatment Diabetic Retinopathy Study (ETDRS) Letters)
    End point type
    Primary
    End point timeframe
    Day 1 to Week 64
    End point values
    KSI-301 (Arm A) Aflibercept (Arm B)
    Number of subjects analysed
    230
    230
    Units: ETDRS Letters
        least squares mean (standard error)
    5.6 ( 0.83 )
    9.5 ( 0.85 )
    Statistical analysis title
    Mean Change in BCVA
    Comparison groups
    KSI-301 (Arm A) v Aflibercept (Arm B)
    Number of subjects included in analysis
    460
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [1]
    P-value
    = 0.4162 [2]
    Method
    Mixed models analysis
    Parameter type
    Adjusted mean difference
    Point estimate
    -3.8
    Confidence interval
         level
    95.04%
         sides
    2-sided
         lower limit
    -5.47
         upper limit
    -2.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.84
    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
    [2] - MMRM model with treatment, visit, treatment by visit interaction, randomization stratification factors, and continuous baseline BCVA and OCT CST.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events (AEs) reported through Week 64 or Early Termination (ET) if occurred before Week 64
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    KSI-301 (Arm A)
    Reporting group description
    Drug: KSI-301 Intravitreal Injection

    Reporting group title
    Aflibercept (Arm B)
    Reporting group description
    Aflibercept: Intravitreal Injection

    Serious adverse events
    KSI-301 (Arm A) Aflibercept (Arm B)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    61 / 230 (26.52%)
    51 / 230 (22.17%)
         number of deaths (all causes)
    5
    5
         number of deaths resulting from adverse events
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Endometrial cancer recurrent
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hodgkin's disease
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine neoplasm
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemangioma
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuroendocrine tumour
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertensive urgency
         subjects affected / exposed
    2 / 230 (0.87%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    0 / 230 (0.00%)
    3 / 230 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Catheter site haemorrhage
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Complication associated with device
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sudden death
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Reproductive system and breast disorders
    Prostatitis
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         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 / 230 (1.30%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 230 (0.87%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    2 / 230 (0.87%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 230 (0.00%)
    2 / 230 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Behaviour disorder
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device malfunction
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Medical observation
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Hip fracture
         subjects affected / exposed
    2 / 230 (0.87%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 230 (0.00%)
    2 / 230 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Burns third degree
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    5 / 230 (2.17%)
    3 / 230 (1.30%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Coronary artery disease
         subjects affected / exposed
    4 / 230 (1.74%)
    5 / 230 (2.17%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    3 / 230 (1.30%)
    2 / 230 (0.87%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    2 / 230 (0.87%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 230 (0.43%)
    2 / 230 (0.87%)
         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 / 230 (0.43%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 230 (0.43%)
         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 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (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 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiorenal syndrome
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congestive cardiomyopathy
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Ischaemic stroke
         subjects affected / exposed
    3 / 230 (1.30%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    2 / 230 (0.87%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aphasia
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Blood and lymphatic system disorders
    Lymphadenopathy mediastinal
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (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 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment - Fellow Eye
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 230 (0.43%)
    3 / 230 (1.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    1 / 230 (0.43%)
    2 / 230 (0.87%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcoholic pancreatitis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic gastroparesis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 230 (0.00%)
    2 / 230 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 230 (0.00%)
    2 / 230 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal fluid collection
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Strangulated umbilical hernia
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    4 / 230 (1.74%)
    6 / 230 (2.61%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    2 / 230 (0.87%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    1 / 230 (0.43%)
    2 / 230 (0.87%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    End stage renal disease
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    0 / 230 (0.00%)
    2 / 230 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Psoriatic arthropathy
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 230 (0.00%)
    2 / 230 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    5 / 230 (2.17%)
    2 / 230 (0.87%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    4 / 230 (1.74%)
    3 / 230 (1.30%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    4 / 230 (1.74%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 230 (1.30%)
    2 / 230 (0.87%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    3 / 230 (1.30%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 230 (1.30%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic gangrene
         subjects affected / exposed
    2 / 230 (0.87%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 230 (0.87%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    2 / 230 (0.87%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metapneumovirus infection
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis acute
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endophthalmitis - Study Eye
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia infection
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Implant site infection
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrotising fasciitis
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    3 / 230 (1.30%)
    3 / 230 (1.30%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 230 (0.43%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 230 (0.43%)
    0 / 230 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemic hyperosmolar nonketotic syndrome
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    0 / 230 (0.00%)
    1 / 230 (0.43%)
         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 (Arm A) Aflibercept (Arm B)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    126 / 230 (54.78%)
    121 / 230 (52.61%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    30 / 230 (13.04%)
    31 / 230 (13.48%)
         occurrences all number
    33
    34
    Eye disorders
    Cataract - Study Eye
         subjects affected / exposed
    35 / 230 (15.22%)
    17 / 230 (7.39%)
         occurrences all number
    38
    17
    Diabetic retinal oedema - Fellow Eye
         subjects affected / exposed
    19 / 230 (8.26%)
    21 / 230 (9.13%)
         occurrences all number
    19
    22
    Conjunctival haemorrhage - Study Eye
         subjects affected / exposed
    18 / 230 (7.83%)
    15 / 230 (6.52%)
         occurrences all number
    21
    21
    Cataract - Fellow Eye
         subjects affected / exposed
    15 / 230 (6.52%)
    12 / 230 (5.22%)
         occurrences all number
    15
    12
    Dry eye - Study Eye
         subjects affected / exposed
    13 / 230 (5.65%)
    10 / 230 (4.35%)
         occurrences all number
    15
    11
    Renal and urinary disorders
    Chronic kidney disease
         subjects affected / exposed
    8 / 230 (3.48%)
    14 / 230 (6.09%)
         occurrences all number
    8
    14
    Infections and infestations
    COVID-19
         subjects affected / exposed
    42 / 230 (18.26%)
    33 / 230 (14.35%)
         occurrences all number
    45
    36
    Nasopharyngitis
         subjects affected / exposed
    8 / 230 (3.48%)
    17 / 230 (7.39%)
         occurrences all number
    8
    18
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    19 / 230 (8.26%)
    17 / 230 (7.39%)
         occurrences all number
    19
    18

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Mar 2022
    Version 2.0 - Changes from Version 1.0 (original protocol) include the following: • The timing for evaluation of the primary objective was extended by 12 weeks, from the average of Weeks 48 and 52 to the average of Weeks 60 and 64. • The disease activity criteria were adjusted and simplified to remove subjectivity and allow for more uniform application of the criteria across all study subjects, as well as to account for patients with persistent retinal edema that is not worsening.

    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.
    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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