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    Clinical Trial Results:
    A Phase IIIb, prospective, interventional, multicentre, three-year study to explore the long-term evolution of sign and symptoms, and occurrence of complications in Dry Eye Disease patients with severe keratitis receiving IKERVIS® (1mg/ml ciclosporin) eye drops

    Summary
    EudraCT number
    		 2017-002660-41
    Trial protocol
    		 CZ   PL   IT  
    Global end of trial date
    14 Jul 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Mar 2024
    First version publication date
    17 Mar 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NVG14L127
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04144413
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Santen S.A.S.
    Sponsor organisation address
    1 Rue Pierre Fontaine, Genavenir IV, 91058 Evry cedex, France, F-91058
    Public contact
    Global Regulatory Affairs Europe, SANTEN SAS, regulatoryaffairs@santen.com
    Scientific contact
    Global Regulatory Affairs Europe, SANTEN SAS, regulatoryaffairs@santen.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
    05 Jan 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Jul 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    1) To evaluate the long-term efficacy of a continuous treatment of IKERVIS® (1mg/mL ciclosporin) eye drops in adult dry eye disease (DED) patients with severe keratitis on corneal sign and DED symptoms, and to estimate the lag time (if any) to improvement in symptoms (if any) 2) To assess the ocular surface complications over the three-year study period.
    Protection of trial subjects
    The study was conducted in accordance with the Declaration of Helsinki and its most recent update, and the International Council for Harmonisation (ICH) E6 Good Clinical Practice (GCP) guideline. The study was also conducted in accordance with local legal and regulatory requirements of the countries involved, and with standard operating procedures in place.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    04 Mar 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 83
    Country: Number of subjects enrolled
    Spain: 74
    Country: Number of subjects enrolled
    Czechia: 65
    Country: Number of subjects enrolled
    Italy: 57
    Country: Number of subjects enrolled
    Russian Federation: 61
    Country: Number of subjects enrolled
    Türkiye: 10
    Worldwide total number of subjects
    350
    EEA total number of subjects
    279
    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)
    209
    From 65 to 84 years
    136
    85 years and over
    5

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 350 DED adult patients with severe keratitis having CFS grade 3 or above on the modified Oxford scale and with at least half of them having a CFS grade 4 or 5 were planned to be enrolled in approximately 52 trial sites in Period 1. It was expected that approximately 70% of the included patients would enter Period 2.

    Period 1
    Period 1 title
    Open-Label Treatment Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Open-label
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    IKERVIS
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Eye drops, emulsion in single-dose container
    Routes of administration
    Ocular use
    Dosage and administration details
    Instillation of one drop in each affected eye, once daily at bedtime. From Baseline for the first 12 months of treatment.

    Number of subjects in period 1
    		Open-label
    Started
    350
    Completed
    288
    Not completed
    62
         Adverse event, serious fatal
    1
         Consent withdrawn by subject
    15
         Non-compliance with Study Drug
    2
         Adverse event, non-fatal
    26
         Other
    1
         Lost to follow-up
    2
         Lack of efficacy
    11
         Protocol deviation
    4
    Period 2
    Period 2 title
    Double-Masked Treatment Period
    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
    		 Masked Ikervis
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    IKERVIS
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Eye drops, emulsion in single-dose container
    Routes of administration
    Ocular use
    Dosage and administration details
    Instillation of one drop in each affected eye, once daily at bedtime.

    Arm title
    		 Masked Vehicle
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Vehicle
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Eye drops, emulsion in single-dose container
    Routes of administration
    Ocular use
    Dosage and administration details
    Instillation of one drop in each affected eye, once daily at bedtime.

    Number of subjects in period 2 [1]
    		Masked Ikervis Masked Vehicle
    Started
    148
    97
    Completed
    137
    86
    Not completed
    11
    11
         Adverse event, serious fatal
    1
    1
         Non-compliance with Study Drug
    3
    1
         Consent withdrawn by subject
    6
    3
         Adverse event, non-fatal
    1
    1
         Other
    -
    1
         Lack of efficacy
    -
    4
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Only Patients who have shown a marked improvement at Month 12 (as defined below) were randomised to receive IKERVIS® or Vehicle (ration 3:2) in double-masked fashion.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Open-Label Treatment Period
    Reporting group description
    		 -

    Reporting group values
    		 Open-Label Treatment Period Total
    Number of subjects
    		 350 350
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 209 209
        From 65-84 years
    		 136 136
        85 years and over
    		 5 5
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 59.5 ± 13.24 -
    Gender categorical
    Units: Subjects
        Female
    		 302 302
        Male
    		 48 48

    End points

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    End points reporting groups
    Reporting group title
    Open-label
    Reporting group description
    		 -
    Reporting group title
    Masked Ikervis
    Reporting group description
    		 -

    Reporting group title
    Masked Vehicle
    Reporting group description
    		 -

    Primary: The correlation CFS score and SANDE symptoms score in Period 1

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    End point title
    		 The correlation CFS score and SANDE symptoms score in Period 1 [1]
    End point description
    The primary efficacy endpoint is the correlation between change from baseline in CFS score and SANDE symptoms score at each visit, and cross correlation of sign at visit X versus symptoms at visit X+i, if any.
    End point type
    Primary
    End point timeframe
    Baseline visit (Day 1), Month 3, Month 6, Month 9, and Month 12
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical testing was conducted for this item measures in this study.
    End point values
    		 Open-label
    Number of subjects analysed
    336 [2]
    Units: Spearman Correlation Coefficient
    number (confidence interval 95%)
        Month 3 / Month 3
    0.169 (0.060 to 0.274)
        Month 3 / Month 6
    0.245 (0.130 to 0.353)
        Month 3 / Month 9
    0.274 (0.160 to 0.380)
        Month 3 / Month 12
    0.178 (0.060 to 0.290)
        Month 6 / Month 6
    0.258 (0.144 to 0.365)
        Month 6 / Month 9
    0.322 (0.209 to 0.426)
        Month 6 / Month 12
    0.274 (0.158 to 0.382)
        Month 9 / Month 9
    0.343 (0.234 to 0.444)
        Month 9 / Month 12
    0.332 (0.221 to 0.434)
        Month 12 / Month 12
    0.266 (0.155 to 0.370)
    Notes
    [2] - The value is the number of subjects in baseline visit.
    No statistical analyses for this end point

    Primary: The correlation CFS score and SANDE symptoms score in Period 2

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    End point title
    		 The correlation CFS score and SANDE symptoms score in Period 2 [3]
    End point description
    The primary efficacy endpoint is the correlation between change from baseline in CFS score and SANDE symptoms score at each visit, and cross correlation of sign at visit X versus symptoms at visit X+i, if any.
    End point type
    Primary
    End point timeframe
    Baseline visit (Month 12), Month 15, Month 18, Month 21,Month 24, Month 27, Month 30,Month 33, Month 36
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical testing was conducted for this item measures in this study.
    End point values
    		 Masked Ikervis Masked Vehicle
    Number of subjects analysed
    148 [4]
    97 [5]
    Units: Spearman Correlation Coefficient
    number (confidence interval 95%)
        Month 15 / Month 15
    0.181 (0.020 to 0.333)
    0.059 (-0.143 to 0.257)
        Month 15 / Month 18
    0.282 (0.123 to 0.427)
    -0.131 (-0.329 to 0.078)
        Month 15 / Month 21
    0.119 (-0.049 to 0.280)
    -0.122 (-0.323 to 0.090)
        Month 15 / Month 24
    0.126 (-0.040 to 0.286)
    -0.014 (-0.222 to 0.195)
        Month 15 / Month 27
    0.182 (0.015 to 0.339)
    -0.050 (-0.257 to 0.161)
        Month 15 / Month 30
    0.073 (-0.097 to 0.239)
    0.028 (-0.184 to 0.237)
        Month 15 / Month 33
    0.141 (-0.028 to 0.302)
    -0.110 (-0.314 to 0.105)
        Month 15 / Month 36
    0.242 (0.076 to 0.395)
    -0.049 (-0.259 to 0.166)
        Month 18 / Month 18
    0.264 (0.103 to 0.411)
    0.152 (-0.058 to 0.350)
        Month 18 / Month 21
    0.248 (0.084 to 0.399)
    0.129 (-0.086 to 0.331)
        Month 18 / Month 24
    0.130 (-0.039 to 0.291)
    0.109 (-0.105 to 0.314)
        Month 18 / Month 27
    0.196 (0.027 to 0.354)
    0.038 (-0.175 to 0.248)
        Month 18 / Month 30
    0.179 (0.008 to 0.339)
    0.069 (-0.146 to 0.278)
        Month 18 / Month 33
    0.237 (0.070 to 0.392)
    0.077 (-0.140 to 0.287)
        Month 18 / Month 36
    0.282 (0.117 to 0.432)
    0.053 (-0.165 to 0.265)
        Month 21 / Month 21
    0.222 (0.058 to 0.374)
    0.184 (-0.026 to 0.377)
        Month 21 / Month 24
    0.157 (-0.009 to 0.315)
    0.027 (-0.183 to 0.234)
        Month 21 / Month 27
    0.243 (0.079 to 0.395)
    0.115 (-0.096 to 0.317)
        Month 21 / Month 30
    0.245 (0.079 to 0.397)
    0.078 (-0.135 to 0.284)
        Month 21 / Month 33
    0.227 (0.061 to 0.381)
    0.053 (-0.160 to 0.262)
        Month 21 / Month 36
    0.271 (0.107 to 0.421)
    0.144 (-0.071 to 0.346)
        Month 24 / Month 24
    0.267 (0.105 to 0.415)
    0.101 (-0.110 to 0.303)
        Month 24 / Month 27
    0.301 (0.140 to 0.447)
    0.094 (-0.118 to 0.298)
        Month 24 / Month 30
    0.192 (0.023 to 0.350)
    0.015 (-0.197 to 0.225)
        Month 24 / Month 33
    0.281 (0.118 to 0.430)
    0.085 (-0.129 to 0.291)
        Month 24 / Month 36
    0.297 (0.134 to 0.444)
    0.127 (-0.088 to 0.331)
        Month 27 / Month 27
    0.292 (0.132 to 0.438)
    0.110 (-0.101 to 0.311)
        Month 27 / Month 30
    0.249 (0.084 to 0.401)
    0.140 (-0.072 to 0.339)
        Month 27 / Month 33
    0.218 (0.052 to 0.372)
    0.191 (-0.021 to 0.386)
        Month 27 / Month 36
    0.284 (0.122 to 0.432)
    0.220 (0.009 to 0.413)
        Month 30 / Month 30
    0.346 (0.188 to 0.487)
    0.135 (-0.076 to 0.335)
        Month 30 / Month 33
    0.187 (0.019 to 0.345)
    0.142 (-0.071 to 0.343)
        Month 30 / Month 36
    0.315 (0.153 to 0.460)
    0.216 (0.004 to 0.409)
        Month 33 / Month 33
    0.248 (0.084 to 0.399)
    0.193 (-0.018 to 0.388)
        Month 33 / Month 36
    0.293 (0.131 to 0.440)
    0.163 (-0.051 to 0.362)
        Month 36 / Month 36
    0.384 (0.231 to 0.519)
    0.264 (0.055 to 0.451)
    Notes
    [4] - The value is the number of subjects in baseline visit.
    [5] - The value is the number of subjects in baseline visit.
    No statistical analyses for this end point

    Primary: The correlation CFS score and SANDE symptoms score Entire Study

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    End point title
    		 The correlation CFS score and SANDE symptoms score Entire Study [6]
    End point description
    End point type
    Primary
    End point timeframe
    Baseline visit, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21,Month 24, Month 27, Month 30,Month 33, and Month 36
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical testing was conducted for this item measures in this study.
    End point values
    		 Masked Ikervis Masked Vehicle
    Number of subjects analysed
    148 [7]
    97 [8]
    Units: Spearman Correlation Coefficient
    number (confidence interval 95%)
        Month 3 / Month 3
    0.159 (-0.006 to 0.316)
    0.097 (-0.110 to 0.296)
        Month 3 / Month 6
    0.124 (-0.047 to 0.288)
    0.254 (0.046 to 0.441)
        Month 3 / Month 9
    0.278 (0.117 to 0.426)
    0.100 (-0.110 to 0.302)
        Month 3 / Month 12
    0.184 (0.019 to 0.339)
    0.028 (-0.178 to 0.232)
        Month 3 / Month 15
    0.241 (0.078 to 0.391)
    0.103 (-0.104 to 0.301)
        Month 3 / Month 18
    0.165 (-0.004 to 0.325)
    0.026 (-0.187 to 0.236)
        Month 3 / Month 21
    0.154 (-0.016 to 0.316)
    -0.041 (-0.253 to 0.175)
        Month 3 / Month 24
    0.074 (-0.096 to 0.241)
    0.066 (-0.150 to 0.275)
        Month 3 / Month 27
    0.107 (-0.064 to 0.272)
    0.045 (-0.171 to 0.257)
        Month 3 / Month 30
    0.179 (0.008 to 0.339)
    -0.003 (-0.217 to 0.212)
        Month 3 / Month 33
    0.183 (0.012 to 0.343)
    -0.013 (-0.228 to 0.203)
        Month 3 / Month 36
    0.052 (-0.121 to 0.221)
    0.092 (-0.128 to 0.303)
        Month 6 / Month 6
    0.173 (0.006 to 0.331)
    0.286 (0.083 to 0.466)
        Month 6 / Month 9
    0.312 (0.150 to 0.457)
    0.240 (0.031 to 0.429)
        Month 6 / Month 12
    0.222 (0.056 to 0.376)
    0.220 (0.012 to 0.409)
        Month 6 / Month 15
    0.296 (0.135 to 0.441)
    0.205 (-0.003 to 0.396)
        Month 6 / Month 18
    0.282 (0.118 to 0.432)
    0.230 (0.016 to 0.423)
        Month 6 / Month 21
    0.304 (0.139 to 0.453)
    0.090 (-0.129 to 0.300)
        Month 6 / Month 24
    0.322 (0.159 to 0.467)
    0.133 (-0.084 to 0.338)
        Month 6 / Month 27
    0.314 (0.149 to 0.462)
    0.117 (-0.101 to 0.325)
        Month 6 / Month 30
    0.223 (0.050 to 0.383)
    0.162 (-0.057 to 0.366)
        Month 6 / Month 33
    0.205 (0.032 to 0.366)
    0.140 (-0.081 to 0.348)
        Month 6 / Month 36
    0.201 (0.027 to 0.363)
    0.245 (0.026 to 0.441)
        Month 9 / Month 9
    0.288 (0.127 to 0.434)
    0.300 (0.099 to 0.478)
        Month 9 / Month 12
    0.186 (0.019 to 0.342)
    0.333 (0.135 to 0.505)
        Month 9 / Month 15
    0.366 (0.211 to 0.503)
    0.357 (0.161 to 0.525)
        Month 9 / Month 18
    0.382 (0.227 to 0.519)
    0.325 (0.124 to 0.500)
        Month 9 / Month 21
    0.286 (0.120 to 0.436)
    0.277 (0.068 to 0.463)
        Month 9 / Month 24
    0.227 (0.058 to 0.384)
    0.333 (0.130 to 0.510)
        Month 9 / Month 27
    0.211 (0.039 to 0.371)
    0.340 (0.135 to 0.516)
        Month 9 / Month 30
    0.211 (0.051 to 0.383)
    0.367 (0.165 to 0.540)
        Month 9 / Month 33
    0.293 (0.125 to 0.445)
    0.284 (0.071 to 0.472)
        Month 9 / Month 36
    0.240 (0.068 to 0.398)
    0.461 (0.270 to 0.617)
        Month 12 / Month 12
    0.160 (-0.001 to 0.314)
    0.174 (-0.027 to 0.361)
        Month 12 / Month 15
    0.266 (0.109 to 0.411)
    0.175 (-0.025 to 0.362)
        Month 12 / Month 18
    0.309 (0.152 to 0.451)
    0.259 (0.056 to 0.441)
        Month 12 / Month 21
    0.196 (0.031 to 0.351)
    0.100 (-0.111 to 0.302)
        Month 12 / Month 24
    0.185 (0.021 to 0.340)
    0.178 (-0.030 to 0.371)
        Month 12 / Month 27
    0.214 (0.048 to 0.368)
    0.161 (-0.049 to 0.358)
        Month 12 / Month 30
    0.239 (0.073 to 0.391)
    0.203 (-0.006 to 0.396)
        Month 12 / Month 33
    0.231 (0.066 to 0.384)
    0.178 (-0.034 to 0.374)
        Month 12 / Month 36
    0.195 (0.027 to 0.352)
    0.250 (0.040 to 0.439)
        Month 15 / Month 15
    0.331 (0.178 to 0.468)
    0.427 (0.247 to 0.578)
        Month 15 / Month 18
    0.384 (0.234 to 0.516)
    0.387 (0.195 to 0.550)
        Month 15 / Month 21
    0.246 (0.083 to 0.397)
    0.257 (0.051 to 0.443)
        Month 15 / Month 24
    0.260 (0.099 to 0.408)
    0.380 (0.187 to 0.545)
        Month 15 / Month 27
    0.298 (0.137 to 0.444)
    0.381 (0.187 to 0.547)
        Month 15 / Month 30
    0.335 (0.176 to 0.477)
    0.406 (0.214 to 0.568)
        Month 15 / Month 33
    0.343 (0.186 to 0.484)
    0.358 (0.158 to 0.529)
        Month 15 / Month 36
    0.347 (0.189 to 0.487)
    0.453 (0.266 to 0.608)
        Month 18 / Month 18
    0.450 (0.307 to 0.572)
    0.469 (0.289 to 0.617)
        Month 18 / Month 21
    0.389 (0.237 to 0.523)
    0.374 (0.176 to 0.543)
        Month 18 / Month 24
    0.276 (0.113 to 0.424)
    0.458 (0.272 to 0.610)
        Month 18 / Month 27
    0.326 (0.165 to 0.469)
    0.414 (0.222 to 0.575)
        Month 18 / Month 30
    0.412 (0.260 to 0.545)
    0.474 (0.290 to 0.624)
        Month 18 / Month 33
    0.413 (0.261 to 0.545)
    0.422 (0.228 to 0.583)
        Month 18 / Month 36
    0.422 (0.270 to 0.553)
    0.532 (0.357 to 0.670)
        Month 21 / Month 21
    0.357 (0.204 to 0.494)
    0.328 (0.128 to 0.502)
        Month 21 / Month 24
    0.306 (0.147 to 0.449)
    0.351 (0.154 to 0.521)
        Month 21 / Month 27
    0.340 (0.183 to 0.480)
    0.395 (0.202 to 0.558)
        Month 21 / Month 30
    0.357 (0.201 to 0.496)
    0.380 (0.184 to 0.547)
        Month 21 / Month 33
    0.330 (0.172 to 0.472)
    0.356 (0.155 to 0.528)
        Month 21 / Month 36
    0.354 (0.197 to 0.493)
    0.493 (0.313 to 0.639)
        Month 24 / Month 24
    0.410 (0.261 to 0.540)
    0.429 (0.243 to 0.585)
        Month 24 / Month 27
    0.395 (0.243 to 0.528)
    0.401 (0.209 to 0.563)
        Month 24 / Month 30
    0.361 (0.204 to 0.500)
    0.388 (0.193 to 0.553)
        Month 24 / Month 33
    0.392 (0.239 to 0.526)
    0.402 (0.207 to 0.565)
        Month 24 / Month 36
    0.422 (0.271 to 0.552)
    0.499 (0.320 to 0.644)
        Month 27 / Month 27
    0.287 (0.126 to 0.433)
    0.260 (0.055 to 0.445)
        Month 27 / Month 30
    0.311 (0.151 to 0.456)
    0.322 (0.121 to 0.498)
        Month 27 / Month 33
    0.243 (0.079 to 0.395)
    0.319 (0.116 to 0.496)
        Month 27 / Month 36
    0.283 (0.120 to 0.431)
    0.423 (0.231 to 0.582)
        Month 30 / Month 30
    0.414 (0.264 to 0.545)
    0.455 (0.271 to 0.607)
        Month 30 / Month 33
    0.272 (0.108 to 0.422)
    0.411 (0.219 to 0.572)
        Month 30 / Month 36
    0.363 (0.206 to 0.502)
    0.515 (0.341 to 0.656)
        Month 33 / Month 33
    0.318 (0.159 to 0.461)
    0.447 (0.261 to 0.601)
        Month 33 / Month 36
    0.354 (0.197 to 0.493)
    0.447 (0.260 to 0.602)
        Month 36 / Month 36
    0.484 (0.343 to 0.603)
    0.521 (0.348 to 0.660)
    Notes
    [7] - The value is the number of subjects in baseline visit.
    [8] - The value is the number of subjects in baseline visit.
    No statistical analyses for this end point

    Secondary: Corneal Fluorescein Staining (CFS) Score in each Visit in Period 1

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    End point title
    		 Corneal Fluorescein Staining (CFS) Score in each Visit in Period 1
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline visit, Month 3, Month 6, Month 9 and Month 12
    End point values
    		 Open-label
    Number of subjects analysed
    336 [9]
    Units: CFS Score
    arithmetic mean (standard error)
        Baseline
    3.62 ± 0.667
        Month 3
    2.24 ± 1.072
        Month 6
    1.72 ± 1.137
        Month 9
    1.42 ± 1.094
        Month 12
    1.14 ± 1.008
    Notes
    [9] - The value is the number of subjects in baseline visit.
    No statistical analyses for this end point

    Secondary: Change From Baseline by Visit for Corneal Fluorescein Staining (CFS) Score in Period 1

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    End point title
    		 Change From Baseline by Visit for Corneal Fluorescein Staining (CFS) Score in Period 1
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline visit, Month 3, Month 6, Month 9 and Month 12
    End point values
    		 Open-label
    Number of subjects analysed
    336 [10]
    Units: CFS Score
    arithmetic mean (standard error)
        Month 3
    -1.38 ± 0.995
        Month 6
    -1.91 ± 1.143
        Month 9
    -2.20 ± 1.123
        Month 12
    -2.49 ± 0.981
    Notes
    [10] - Baseline number.
    No statistical analyses for this end point

    Secondary: Corneal Fluorescein Staining (CFS) Score in each Visit in Period 2

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    End point title
    		 Corneal Fluorescein Staining (CFS) Score in each Visit in Period 2
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline visit (Month 12), Month 15, Month 18, Month 21,Month 24, Month 27, Month 30,Month 33, and Month 36
    End point values
    		 Masked Ikervis Masked Vehicle
    Number of subjects analysed
    148 [11]
    97 [12]
    Units: CFS score
    arithmetic mean (standard error)
        Baseline visit (Month 12)
    0.91 ± 0.731
    0.86 ± 0.684
        Month 15
    0.95 ± 0.871
    1.06 ± 1.083
        Month 18
    1.00 ± 1.019
    1.04 ± 0.939
        Month 21
    0.93 ± 0.881
    0.83 ± 0.754
        Month 24
    0.99 ± 0.980
    0.90 ± 0.947
        Month 27
    0.80 ± 0.836
    0.95 ± 0.977
        Month 30
    0.86 ± 0.884
    0.83 ± 0.937
        Month 33
    0.86 ± 0.931
    0.89 ± 1.088
        Month 36
    0.87 ± 0.978
    0.81 ± 1.044
    Notes
    [11] - The value is the number of subjects in baseline visit.
    [12] - The value is the number of subjects in baseline visit.
    No statistical analyses for this end point

    Secondary: Change From Baseline by Visit for Corneal Fluorescein Staining (CFS) Score in Period 2

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    End point title
    		 Change From Baseline by Visit for Corneal Fluorescein Staining (CFS) Score in Period 2
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline visit (Month 12), Month 15, Month 18, Month 21,Month 24, Month 27, Month 30,Month 33, and Month 36
    End point values
    		 Masked Ikervis Masked Vehicle
    Number of subjects analysed
    148 [13]
    97 [14]
    Units: CFS Score
    arithmetic mean (standard error)
        Month 15
    -0.05 ± 0.068
    0.10 ± 0.083
        Month 18
    -0.01 ± 0.074
    0.12 ± 0.090
        Month 21
    -0.07 ± 0.067
    -0.07 ± 0.082
        Month 24
    -0.02 ± 0.077
    0.04 ± 0.094
        Month 27
    -0.19 ± 0.073
    0.06 ± 0.090
        Month 30
    -0.12 ± 0.075
    -0.05 ± 0.092
        Month 33
    -0.13 ± 0.079
    0.02 ± 0.098
        Month 36
    -0.12 ± 0.082
    -0.05 ± 0.101
    Notes
    [13] - Baseline number.
    [14] - Baseline number.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Incidence and severity of ocular and systemic adverse events (AEs) over the three-year study period.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Period 1: Open-Label
    Reporting group description
    		 -

    Reporting group title
    Period 2: Masked Ikervis
    Reporting group description
    		 -

    Reporting group title
    Period 2: Masked Vehicle
    Reporting group description
    		 -

    Serious adverse events
    		 Period 1: Open-Label Period 2: Masked Ikervis Period 2: Masked Vehicle
    Total subjects affected by serious adverse events
         subjects affected / exposed
    15 / 344 (4.36%)
    12 / 147 (8.16%)
    9 / 97 (9.28%)
         number of deaths (all causes)
    1
    0
    1
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    1 / 97 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 344 (0.29%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colorectal cancer
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Extranodal marginal zone B-cell lymphoma (MALT type)
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Hip arthroplasty
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery bypass
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Genital prolapse
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Pelvic fracture
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Myocardial infarction
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Brain stem stroke
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Superior sagittal sinus thrombosis
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Posterior capsule opacification
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retinal haemorrhage
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incarcerated inguinal hernia
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    4 / 344 (1.16%)
    2 / 147 (1.36%)
    1 / 97 (1.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sialoadenitis
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Period 1: Open-Label Period 2: Masked Ikervis Period 2: Masked Vehicle
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    138 / 344 (40.12%)
    58 / 147 (39.46%)
    39 / 97 (40.21%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Eyelid haemangioma
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Gastrointestinal lymphoma
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Lymphoedema
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Varicose ulceration
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    1
    0
    1
    Arteriosclerosis
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Hypertension
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Surgical and medical procedures
    Lens extraction
         subjects affected / exposed
    0 / 344 (0.00%)
    2 / 147 (1.36%)
    0 / 97 (0.00%)
         occurrences all number
    0
    2
    0
    Cataract operation
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Hip surgery
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Foot operation
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    General disorders and administration site conditions
    Instillation site pain
         subjects affected / exposed
    3 / 344 (0.87%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    3
    0
    0
    Fatigue
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Instillation site paraesthesia
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Product intolerance
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 344 (0.29%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    1
    1
    0
    Discomfort
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    2 / 344 (0.58%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    2
    0
    0
    Seasonal allergy
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Reproductive system and breast disorders
    Adnexa uteri cyst
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Metrorrhagia
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    2 / 344 (0.58%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    2
    0
    0
    Asthma
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    1
    0
    1
    Dyspnoea
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Pharyngeal oedema
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Sleep apnoea syndrome
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Cough
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Vocal cord inflammation
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Depression
         subjects affected / exposed
    1 / 344 (0.29%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    1
    1
    0
    Investigations
    Blood cholesterol
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Blood pressure decreased
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    SARS-CoV-2 test positive
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    1 / 97 (1.03%)
         occurrences all number
    0
    1
    1
    Body temperature increased
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Vital dye staining cornea present
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    White blood cell count decreased
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Injury, poisoning and procedural complications
    Foreign body in eye
         subjects affected / exposed
    2 / 344 (0.58%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    2
    0
    1
    Animal bite
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Soft tissue foreign body
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Tendon rupture
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Accidental overdose
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Contusion
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Fall
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Cardiac disorders
    Arrhythmia
         subjects affected / exposed
    2 / 344 (0.58%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    2
    0
    0
    Atrial fibrillation
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Nervous system disorders
    Facial paralysis
         subjects affected / exposed
    2 / 344 (0.58%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    2
    0
    0
    Dizziness
         subjects affected / exposed
    1 / 344 (0.29%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    1
    1
    0
    Facial neuralgia
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Headache
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Migraine
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Migraine with aura
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Somnolence
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 344 (0.00%)
    2 / 147 (1.36%)
    0 / 97 (0.00%)
         occurrences all number
    0
    2
    0
    Eye disorders
    Eye irritation
         subjects affected / exposed
    26 / 344 (7.56%)
    4 / 147 (2.72%)
    0 / 97 (0.00%)
         occurrences all number
    28
    4
    0
    Eye pain
         subjects affected / exposed
    16 / 344 (4.65%)
    0 / 147 (0.00%)
    2 / 97 (2.06%)
         occurrences all number
    18
    0
    2
    Dry eye
         subjects affected / exposed
    15 / 344 (4.36%)
    3 / 147 (2.04%)
    5 / 97 (5.15%)
         occurrences all number
    15
    3
    5
    Eye pruritus
         subjects affected / exposed
    12 / 344 (3.49%)
    3 / 147 (2.04%)
    1 / 97 (1.03%)
         occurrences all number
    12
    4
    1
    Ocular hyperaemia
         subjects affected / exposed
    11 / 344 (3.20%)
    3 / 147 (2.04%)
    0 / 97 (0.00%)
         occurrences all number
    11
    3
    0
    Visual acuity reduced
         subjects affected / exposed
    4 / 344 (1.16%)
    3 / 147 (2.04%)
    3 / 97 (3.09%)
         occurrences all number
    5
    4
    3
    Conjunctival hyperaemia
         subjects affected / exposed
    4 / 344 (1.16%)
    1 / 147 (0.68%)
    2 / 97 (2.06%)
         occurrences all number
    4
    1
    2
    Lacrimation increased
         subjects affected / exposed
    3 / 344 (0.87%)
    1 / 147 (0.68%)
    1 / 97 (1.03%)
         occurrences all number
    4
    1
    1
    Vision blurred
         subjects affected / exposed
    4 / 344 (1.16%)
    3 / 147 (2.04%)
    1 / 97 (1.03%)
         occurrences all number
    4
    3
    1
    Abnormal sensation in eye
         subjects affected / exposed
    3 / 344 (0.87%)
    1 / 147 (0.68%)
    1 / 97 (1.03%)
         occurrences all number
    3
    1
    1
    Chalazion
         subjects affected / exposed
    3 / 344 (0.87%)
    1 / 147 (0.68%)
    2 / 97 (2.06%)
         occurrences all number
    3
    2
    2
    Conjunctival oedema
         subjects affected / exposed
    3 / 344 (0.87%)
    1 / 147 (0.68%)
    1 / 97 (1.03%)
         occurrences all number
    3
    1
    1
    Ocular discomfort
         subjects affected / exposed
    3 / 344 (0.87%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    3
    1
    0
    Blepharospasm
         subjects affected / exposed
    2 / 344 (0.58%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    2
    0
    0
    Corneal leukoma
         subjects affected / exposed
    2 / 344 (0.58%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    2
    0
    0
    Corneal oedema
         subjects affected / exposed
    2 / 344 (0.58%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    2
    0
    0
    Eyelid oedema
         subjects affected / exposed
    2 / 344 (0.58%)
    1 / 147 (0.68%)
    1 / 97 (1.03%)
         occurrences all number
    2
    1
    1
    Eyelids pruritus
         subjects affected / exposed
    2 / 344 (0.58%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    2
    0
    1
    Foreign body sensation in eyes
         subjects affected / exposed
    2 / 344 (0.58%)
    3 / 147 (2.04%)
    2 / 97 (2.06%)
         occurrences all number
    2
    3
    2
    Keratitis
         subjects affected / exposed
    2 / 344 (0.58%)
    1 / 147 (0.68%)
    2 / 97 (2.06%)
         occurrences all number
    2
    1
    2
    Lenticular opacities
         subjects affected / exposed
    2 / 344 (0.58%)
    2 / 147 (1.36%)
    0 / 97 (0.00%)
         occurrences all number
    2
    2
    0
    Meibomian gland dysfunction
         subjects affected / exposed
    2 / 344 (0.58%)
    1 / 147 (0.68%)
    1 / 97 (1.03%)
         occurrences all number
    2
    1
    1
    Noninfective conjunctivitis
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    2
    0
    1
    Photophobia
         subjects affected / exposed
    2 / 344 (0.58%)
    3 / 147 (2.04%)
    1 / 97 (1.03%)
         occurrences all number
    2
    3
    1
    Blepharitis
         subjects affected / exposed
    1 / 344 (0.29%)
    5 / 147 (3.40%)
    3 / 97 (3.09%)
         occurrences all number
    1
    5
    5
    Cataract
         subjects affected / exposed
    1 / 344 (0.29%)
    5 / 147 (3.40%)
    0 / 97 (0.00%)
         occurrences all number
    1
    6
    0
    Conjunctivitis allergic
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Dacryolith
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Dermatochalasis
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Eczema eyelids
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Erythema of eyelid
         subjects affected / exposed
    1 / 344 (0.29%)
    1 / 147 (0.68%)
    1 / 97 (1.03%)
         occurrences all number
    1
    1
    1
    Lacrimation disorder
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Ocular hypertension
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Pinguecula
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Lacrimal disorder
         subjects affected / exposed
    0 / 344 (0.00%)
    2 / 147 (1.36%)
    2 / 97 (2.06%)
         occurrences all number
    0
    3
    3
    Posterior capsule opacification
         subjects affected / exposed
    0 / 344 (0.00%)
    2 / 147 (1.36%)
    2 / 97 (2.06%)
         occurrences all number
    0
    2
    2
    Corneal degeneration
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Diplopia
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Episcleritis
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Eye allergy
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Meibomianitis
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Vitreoretinal traction syndrome
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Eyelash discolouration
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Macular cyst
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Meibomian gland discharge
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Photopsia
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Retinal degeneration
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Trichiasis
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Gastrointestinal disorders
    Dyspepsia
         subjects affected / exposed
    2 / 344 (0.58%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    2
    1
    0
    Food poisoning
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Nausea
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Stomatitis
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    1 / 344 (0.29%)
    2 / 147 (1.36%)
    0 / 97 (0.00%)
         occurrences all number
    1
    2
    0
    Hand dermatitis
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Photosensitivity reaction
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Rash
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Dandruff
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Eczema
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Renal and urinary disorders
    Urinary incontinence
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Renal cyst
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    1
    0
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    4 / 344 (1.16%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    4
    2
    0
    Arthralgia
         subjects affected / exposed
    2 / 344 (0.58%)
    1 / 147 (0.68%)
    1 / 97 (1.03%)
         occurrences all number
    2
    1
    1
    Fibromyalgia
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Neck pain
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Pain in extremity
         subjects affected / exposed
    1 / 344 (0.29%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    1
    1
    0
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Osteoporosis
         subjects affected / exposed
    0 / 344 (0.00%)
    2 / 147 (1.36%)
    0 / 97 (0.00%)
         occurrences all number
    0
    2
    0
    Systemic lupus erythematosus
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    1 / 97 (1.03%)
         occurrences all number
    0
    1
    1
    Foot deformity
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Meniscal degeneration
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Osteoarthritis
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Plantar fasciitis
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Infections and infestations
    COVID-19
         subjects affected / exposed
    8 / 344 (2.33%)
    10 / 147 (6.80%)
    5 / 97 (5.15%)
         occurrences all number
    8
    11
    5
    Conjunctivitis
         subjects affected / exposed
    4 / 344 (1.16%)
    3 / 147 (2.04%)
    2 / 97 (2.06%)
         occurrences all number
    5
    4
    2
    Nasopharyngitis
         subjects affected / exposed
    3 / 344 (0.87%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    4
    1
    0
    Hordeolum
         subjects affected / exposed
    3 / 344 (0.87%)
    1 / 147 (0.68%)
    1 / 97 (1.03%)
         occurrences all number
    3
    3
    1
    Bronchitis
         subjects affected / exposed
    2 / 344 (0.58%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    2
    0
    1
    Herpes zoster
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    2
    0
    1
    Viral infection
         subjects affected / exposed
    2 / 344 (0.58%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    2
    1
    0
    Asymptomatic COVID-19
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Eye infection viral
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Eyelid infection
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Influenza
         subjects affected / exposed
    1 / 344 (0.29%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    1
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Rhinitis
         subjects affected / exposed
    1 / 344 (0.29%)
    2 / 147 (1.36%)
    0 / 97 (0.00%)
         occurrences all number
    1
    2
    0
    Tooth abscess
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    1
    0
    1
    Urinary tract infection
         subjects affected / exposed
    1 / 344 (0.29%)
    2 / 147 (1.36%)
    1 / 97 (1.03%)
         occurrences all number
    1
    2
    1
    Wound infection
         subjects affected / exposed
    1 / 344 (0.29%)
    0 / 147 (0.00%)
    0 / 97 (0.00%)
         occurrences all number
    1
    0
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 344 (0.00%)
    2 / 147 (1.36%)
    0 / 97 (0.00%)
         occurrences all number
    0
    2
    0
    Pharyngitis
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    1 / 97 (1.03%)
         occurrences all number
    0
    1
    1
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Helicobacter infection
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Herpes ophthalmic
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Lyme disease
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Ophthalmic herpes zoster
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Tonsillitis
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Varicella
         subjects affected / exposed
    0 / 344 (0.00%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    0
    1
    0
    Borrelia infection
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Gastroenteritis viral
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Parotitis
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Postoperative wound infection
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Suspected COVID-19
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 344 (0.00%)
    0 / 147 (0.00%)
    1 / 97 (1.03%)
         occurrences all number
    0
    0
    1
    Metabolism and nutrition disorders
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 344 (0.29%)
    1 / 147 (0.68%)
    0 / 97 (0.00%)
         occurrences all number
    1
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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 reported
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    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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