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    Clinical Trial Results:
    To evaluate the safety and effectiveness of human ex vivo expanded autologous limbal stem cells for the treatment of unilateral total limbal stem cell deficiency.

    Summary
    EudraCT number
    		 2011-000608-16
    Trial protocol
    		 GB  
    Global end of trial date
    09 Feb 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Jun 2024
    First version publication date
    02 Jun 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    5466
    Additional study identifiers
    ISRCTN number
    		 ISRCTN51772481
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    The Newcastle upon Tyne Hospitals NHS Foundation Trust
    Sponsor organisation address
    Regent Point, Regent Farm Road, Gosforth, Newcastle upon Tyne, United Kingdom, NE3 3HD
    Public contact
    Prof Francisco Figueiredo, The Newcastle upon Tyne Hospitals NHS Foundation Trust, 0191 282 5582, f.c.figueiredo@ncl.ac.uk
    Scientific contact
    Prof Francisco Figueiredo, The Newcastle upon Tyne Hospitals NHS Foundation Trust, 0191 282 5582, f.c.figueiredo@ncl.ac.uk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    17 Jan 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    09 Feb 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Feb 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety and efficacy (or capacity to produce a desired effect) of ex vivo expanded autologous Limbal Stem Cells transplantation (transplant derived from the same patient, animal free and grown ex vivo or outside the body) for the treatment of unilateral total Limbal Stem Cell Deficiency (a severe corneal disease resulting in painful blindness). The product is manufactured according to GMP guidelines and under a Quality Management System.
    Protection of trial subjects
    All non-serious adverse events/reaction will be recorded at all visits up to visit 7 at 12 months and all non-serious adverse reactions from visit 7 at 12 months to visit 10 at 36 months. Any serious adverse events will be recorded throughout the duration of the study until 36 months.
    Background therapy
    		 Ex vivo expansion of autologous limbal stem cells transplantation on amniotic membrane has been used in a few centres around the world, including the UK for the treatment of unilateral total limbal stem cell deficiency, even though this is an unlicensed indication. For purposes of this study, Ex vivo expansion of autologous limbal stem cells transplantation on amniotic membrane is both an Advanced Therapeutic Medicinal Product (ATMP) and an Investigational Medicinal Product and thus it meets the combined definition of an Advanced Therapeutic Investigational Medicinal Product (ATIMP) Regulation (EU) No 1394/2007.
    Evidence for comparator
    		 Corneal vascularisation and opacity cause blindness in ~8 million people worldwide pa, but the importance of limbal stem cells (LSC), and the symptoms of their dysfunction as a major cause of corneal blindness, have been appreciated only recently. In LSC deficiency (LSCD), reduced vision is due to corneal pathology as the eye is otherwise healthy; effective treatment of LSCD and associated corneal scarring would restore vision. This group has developed a system to culture human limbal epithelium without the use of animal cells/products, and has successfully transplanted nine patients with unilateral severe LSCD. Autologous human serum drops, from patients’ blood, and the culture medium, are used post-operatively to treat any ocular surface problems. Significantly declined symptom severity, significant improvement in visual impairment scores, and in Snellen visual acuity, were observed. Corneal impression cytology at six months post-procedure confirmed the reversal of conjunctivalisation. Treatment of severe symptomatic total LSCD is mainly surgical – a limbal tissue autograft from the patient’s healthy other eye. In bilateral LSCD, allografts from living related/cadaveric donors are used, with potent immunosuppression. However, much healthy tissue is required, potentially causing LSCD in the donor. Recently, small amounts of healthy human limbal epithelium have been expanded ex vivo in culture to form epithelial sheets, and transplanted, with reduced risk of donor LSCD. This formal clinical trial aims to establish transplantation of cultured limbal epithelium as a clinical treatment option for LSCD. Most current techniques also use animal products, precluding their clinical use to treat UK patients legally. There is also an increasing need to substitute animal-based products during the ex vivo expansion of the cells, due to the risk of transmission of retroviruses, other pathogens or other infectious agents to patients and the wider population.
    Actual start date of recruitment
    30 May 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 27
    Worldwide total number of subjects
    27
    EEA total number of subjects
    27
    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)
    25
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The recruitment period ran from 15 May 2012 to 05 January 2015 from one NHS hospital site in the United Kingdom. This was the Royal Victoria Infirmary in Newcastle upon Tyne (The Newcastle upon Tyne Hospitals NHS Foundation Trust).

    Pre-assignment
    Screening details
    		 Potential participants were identified by the CI via routine clinic outpatient appointments. The CI/Co-I/Authorised Delegate explained the study to eligible patients. Eligibility screening forms were completed, to document patients' fulfilment of the eligibility criteria, whether included or not.

    Period 1
    Period 1 title
    Baseline
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    Not applicable

    Arms
    Arm title
    		 LSC Transplant
    Arm description
    		 -
    Arm type
    		 surgical intervention

    Investigational medicinal product name
    Autologous LSC transplant
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ophthalmic insert
    Routes of administration
    Route of administration not applicable
    Dosage and administration details
    Autologous Limbal Stem Cell (LSC) transplantation

    Number of subjects in period 1
    		LSC Transplant
    Started
    27
    Biopsy
    26
    Completed
    23
    Not completed
    4
         No cell growth
    2
         failed biopsy
    1
         Consent withdrawn by subject
    1
    Period 2
    Period 2 title
    6 months
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    Not applicable

    Arms
    Arm title
    		 LSC Transplant
    Arm description
    		 -
    Arm type
    		 surgical intervention

    Investigational medicinal product name
    Autologous LSC transplant
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ophthalmic insert
    Routes of administration
    Route of administration not applicable
    Dosage and administration details
    Autologous Limbal Stem Cell (LSC) transplantation

    Number of subjects in period 2
    		LSC Transplant
    Started
    23
    Completed
    23
    Period 3
    Period 3 title
    12 months
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    Not applicable

    Arms
    Arm title
    		 LSC Transplant
    Arm description
    		 -
    Arm type
    		 surgical intervention

    Investigational medicinal product name
    Autologous LSC transplant
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ophthalmic insert
    Routes of administration
    Route of administration not applicable
    Dosage and administration details
    Autologous Limbal Stem Cell (LSC) transplantation

    Number of subjects in period 3
    		LSC Transplant
    Started
    23
    Completed
    23
    Period 4
    Period 4 title
    36 months
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    Not applicable

    Arms
    Arm title
    		 LSC Transplant
    Arm description
    		 -
    Arm type
    		 surgical intervention

    Investigational medicinal product name
    Autologous LSC transplant
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ophthalmic insert
    Routes of administration
    Route of administration not applicable
    Dosage and administration details
    Autologous Limbal Stem Cell (LSC) transplantation

    Number of subjects in period 4
    		LSC Transplant
    Started
    23
    Completed
    22
    Not completed
    1
         Lost to follow-up
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Baseline
    Reporting group description
    		 -

    Reporting group values
    		 Baseline Total
    Number of subjects
    		 27 27
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 44.5 (29.9 to 51.5) -
    Gender categorical
    Units: Subjects
        Female
    		 5 5
        Male
    		 22 22
    Race
    Units: Subjects
        White/Caucasian
    		 27 27
    Currently employed
    Units: Subjects
        Yes
    		 11 11
        No
    		 9 9
        Stopped due to LSCD
    		 7 7
    Occupation
    Units: Subjects
        Professional
    		 1 1
        Technical
    		 4 4
        Administrative
    		 2 2
        Labourer
    		 7 7
        Sales
    		 1 1
        Housewife/ husband
    		 2 2
        Retired
    		 5 5
        Other
    		 4 4
        Unknown
    		 1 1
    Ophtmalmic history at screening- Eye affected
    Units: Subjects
        Right
    		 14 14
        Left
    		 13 13
    Cause of LSCD
    Units: Subjects
        Chemical burn
    		 21 21
        Thermal burn
    		 4 4
        Iatrogenic
    		 1 1
        Infection
    		 1 1

    End points

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    End points reporting groups
    Reporting group title
    LSC Transplant
    Reporting group description
    		 -
    Reporting group title
    LSC Transplant
    Reporting group description
    		 -
    Reporting group title
    LSC Transplant
    Reporting group description
    		 -
    Reporting group title
    LSC Transplant
    Reporting group description
    		 -

    Primary: The percent of subjects with treatment emergent ocular AEs

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    End point title
    		 The percent of subjects with treatment emergent ocular AEs [1]
    End point description
    The percent of subjects with treatment emergent ocular AEs.
    End point type
    Primary
    End point timeframe
    12 months.
    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: Descriptive summary is only available.
    End point values
    		 LSC Transplant
    Number of subjects analysed
    27
    Units: Percentage points
    10
    No statistical analyses for this end point

    Primary: Ocular surface pain/discomfort

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    End point title
    		 Ocular surface pain/discomfort
    End point description
    The first end-point of the phase II clinical trial will assess changes of patients' reported outcomes: ocular surface pain/discomfort (the primary outcome on which the study was powered) and visual impairment scores from baseline to visit 7 at 12 months. This will be measured in both cases using an analogue scale, which has already been validated in the phase I component of the project (Attachment III).
    End point type
    Primary
    End point timeframe
    baseline to visit 7 at 12 months
    End point values
    		 LSC Transplant LSC Transplant
    Number of subjects analysed
    26 [2]
    23
    Units: number
        median (inter-quartile range (Q1-Q3))
    62.5 (50 to 75)
    75 (62.5 to 100)
    Notes
    [2] - 1 missing result
    Statistical analysis title
    		 Difference in Pain
    Statistical analysis description
    The change in pain between baseline and Visit 7 (12 months post-op) was recorded by ‘ocular pain’ in the National Eye Institute – Visual Function Questionnaire and a Visual Analogue Score for pain. A high score for the Visual Function Questionnaire indicates better functioning and the percentage recorded is the achieved percentage of a total possible score.
    Comparison groups
    LSC Transplant v LSC Transplant
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.02
    Method
    		 Wilcoxon signed ranks test
    Confidence interval

    Primary: Visual impairment score

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    End point title
    		 Visual impairment score [3]
    End point description
    The first end-point of the phase II clinical trial will assess changes of patients' reported outcomes: ocular surface pain/discomfort (the primary outcome on which the study was powered) and visual impairment scores from baseline to visit 7 at 12 months. This will be measured in both cases using an analogue scale, which has already been validated in the phase I component of the project (Attachment III).
    End point type
    Primary
    End point timeframe
    12 months and 36 months.
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive summary is only available.
    End point values
    		 LSC Transplant
    Number of subjects analysed
    23
    Units: number
        median (inter-quartile range (Q1-Q3))
    -1 (-3 to 0)
    No statistical analyses for this end point

    Primary: Corneal impression cytology

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    End point title
    		 Corneal impression cytology [4]
    End point description
    The second end point will be the reversal of LSCD by corneal impression cytology at 6 months post-operatively.
    End point type
    Primary
    End point timeframe
    Six months, post-operative.
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive summary is only available.
    End point values
    		 LSC Transplant
    Number of subjects analysed
    23
    Units: number
        number (confidence interval 95%)
    70.3 (49.8 to 86.2)
    No statistical analyses for this end point

    Primary: Corneal re-epithelialisation

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    End point title
    		 Corneal re-epithelialisation [5]
    End point description
    The third end point is ocular surface reconstruction (i.e. corneal re-epithelialisation).
    End point type
    Primary
    End point timeframe
    12 months and 36 months
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive summary is only available.
    End point values
    		 LSC Transplant LSC Transplant LSC Transplant
    Number of subjects analysed
    22 [6]
    22 [7]
    21 [8]
    Units: number
        number (confidence interval 95%)
    81.4 (61.9 to 93.7)
    85.1 (66.3 to 95.8)
    77.8 (57.7 to 91.4)
    Notes
    [6] - 22 patients in ITT group
    [7] - 22 patients in ITT group
    [8] - 21 patients analysed in ITT group
    No statistical analyses for this end point

    Secondary: Best corrected visual acuity

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    End point title
    		 Best corrected visual acuity
    End point description
    Changes over the same period in best corrected visual acuity, reversal in central corneal vascularisation, reduction in corneal opacity, improvement in patient's reported outcomes, assessment of corneal opacity by anterior segment OCT, assessment of corneal/limbal epithelia by confocal microscopy and potential side effects as described in the case for support.
    End point type
    Secondary
    End point timeframe
    12 months and 36 months.
    End point values
    		 LSC Transplant LSC Transplant
    Number of subjects analysed
    21
    13
    Units: number
        median (inter-quartile range (Q1-Q3))
    -0.04 (-0.82 to 0.14)
    -0.3 (-0.8 to -0.06)
    Statistical analysis title
    		 Change in LogMAR score
    Statistical analysis description
    Wilcoxon signed ranks test
    Comparison groups
    LSC Transplant v LSC Transplant
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1
    Method
    		 Wilcoxon signed ranks test
    Confidence interval

    Secondary: Reversal in central corneal vascularisation

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    End point title
    		 Reversal in central corneal vascularisation
    End point description
    Changes over the same period in best corrected visual acuity, reversal in central corneal vascularisation, reduction in corneal opacity, improvement in patient's reported outcomes, assessment of corneal opacity by anterior segment OCT, assessment of corneal/limbal epithelia by confocal microscopy and potential side effects as described in the case for support. Central corneal neovascularisation (new vessel formation, crossing the limbus onto the clear cornea by ≥ 2mm) (Akpek EK et al. 2004) will be categorised: 0 Absent No evidence of new vessel formation 1 Mild Presence of neovascularisation in 1 quadrant of cornea 2 Moderate Presence of neovascularisation in 2 quadrants of cornea 3 Severe Presence of neovascularisation in ≥ 3 quadrants of cornea
    End point type
    Secondary
    End point timeframe
    12 months and 36 months.
    End point values
    		 LSC Transplant LSC Transplant LSC Transplant LSC Transplant
    Number of subjects analysed
    26 [9]
    23
    23
    22
    Units: number
        Absent
    1
    13
    11
    10
        Mild
    1
    6
    6
    8
        Moderate
    4
    2
    3
    2
        Severe
    20
    2
    3
    1
    Notes
    [9] - missing result from 1 patient
    No statistical analyses for this end point

    Secondary: Reduction in corneal opacity

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    End point title
    		 Reduction in corneal opacity
    End point description
    Changes over the same period in best corrected visual acuity, reversal in central corneal vascularisation, reduction in corneal opacity, improvement in patient's reported outcomes, assessment of corneal opacity by anterior segment OCT, assessment of corneal/limbal epithelia by confocal microscopy and potential side effects as described in the case for support. Corneal opacity will be categorised as: 0 Clear cornea +1 Mild scarring +2 Moderate scarring, iris details still visible +3 Moderate scarring, iris details obscured +4 Marked corneal scarring, iris not visible
    End point type
    Secondary
    End point timeframe
    12 months and 36 months.
    End point values
    		 LSC Transplant LSC Transplant LSC Transplant LSC Transplant
    Number of subjects analysed
    27 [10]
    23
    23 [11]
    22
    Units: number
        Clear Cornea
    0
    0
    1
    10
        Mild Scarring
    1
    4
    3
    9
        Moderate scarring, iris details still visible
    6
    10
    8
    2
        Moderate scarring, iris details obscured
    16
    6
    7
    1
        Marked corneal scarring, iris not visible
    3
    3
    3
    0
    Notes
    [10] - missing result from 1 patient
    [11] - missing result from 1 patient
    No statistical analyses for this end point

    Secondary: Improvement in patient-reported outcomes

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    End point title
    		 Improvement in patient-reported outcomes
    End point description
    Ocular surface disease impact questionnaire
    End point type
    Secondary
    End point timeframe
    12 months and 36 months.
    End point values
    		 LSC Transplant LSC Transplant LSC Transplant LSC Transplant
    Number of subjects analysed
    23 [12]
    22 [13]
    23
    21 [14]
    Units: number
        median (inter-quartile range (Q1-Q3))
    36.1 (20 to 52.1)
    30.7 (21.7 to 38.9)
    29.2 (13.9 to 46.7)
    23.5 (17.1 to 44.6)
    Notes
    [12] - 4 patient results missing
    [13] - 1 missing result
    [14] - missing result for 2 patients
    No statistical analyses for this end point

    Secondary: Assessment of corneal opacity by anterior segment OCT

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    End point title
    		 Assessment of corneal opacity by anterior segment OCT
    End point description
    Assessment of corneal opacity by anterior segment OCT: Scale 0-4 0= clear cornea 1= mild scarring 2= moderate scarring, iris details still visible, 3=moderate scarring, iris details obscured 4= marked corneal scarring, iris not visible
    End point type
    Secondary
    End point timeframe
    12 months and 36 months.
    End point values
    		 LSC Transplant LSC Transplant LSC Transplant LSC Transplant
    Number of subjects analysed
    26 [15]
    23
    22 [16]
    22
    Units: number
        Clear cornea
    0
    0
    1
    10
        mild scarring
    1
    4
    3
    9
        moderate scarring, iris details still visible
    6
    10
    8
    2
        moderate scarring, iris details obscured
    16
    6
    7
    1
        marked corneal scarring, iris not visible
    3
    3
    3
    0
    Notes
    [15] - missing result from 1 patient
    [16] - missing result from 1 patient
    No statistical analyses for this end point

    Secondary: Improvement in patient-reported outcomes: National Eye Institute Visual Function Questionnaire

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    End point title
    		 Improvement in patient-reported outcomes: National Eye Institute Visual Function Questionnaire
    End point description
    National Eye Institute Visual Function Questionnaire
    End point type
    Secondary
    End point timeframe
    Baseline, 6 months, 12 months and 36 months
    End point values
    		 LSC Transplant LSC Transplant LSC Transplant LSC Transplant
    Number of subjects analysed
    23 [17]
    23
    23
    21 [18]
    Units: number
        median (inter-quartile range (Q1-Q3))
    73.4 (56.7 to 83.8)
    78.8 (58.7 to 84.3)
    79.2 (56 to 87.6)
    79.6 (64.9 to 89.4)
    Notes
    [17] - results missing from 4 patients
    [18] - 2 results missing
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Assessment of adverse events will be performed at follow-up visits.
    Adverse event reporting additional description
    AEs will be assessed at each trial follow-up visit, in person.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 Verbatim
    Dictionary version
    1.0
    Reporting groups
    Reporting group title
    LSC Transplant
    Reporting group description
    		 In summary: - there were 42 reported AE in 18 (78% of 23) unique patients - there were 10 AE related (possibly, probably or definitely) to intervention reported in 7 (30% of 23) unique patients.

    Serious adverse events
    		 LSC Transplant
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 27 (37.04%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Injury, poisoning and procedural complications
    left eye blunt injury with rupture of corneal graft wound
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    Cellulitis right elbow
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Eye disorders
    Right corneal graft rejection
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    left corneal ulcer, severe ocular surface inflammation? cornea graft rejection
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Left cornea ulcer with hypopyon
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Left corneal graft rejection
         subjects affected / exposed
    2 / 27 (7.41%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Left cornea ulcer
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Right corneal graft rejection/neurotrophic keratopathy
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Perforation of corneal ulcer in the R eye.
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Patient attempted suicide by drug overdose
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 LSC Transplant
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    18 / 27 (66.67%)
    Surgical and medical procedures
    Patient had R hand surgery due to osteoarthitis as a day case on 06/02/14
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Eye disorders
    Diplopia
         subjects affected / exposed
    2 / 27 (7.41%)
         occurrences all number
    2
    Epithelial defect + Associated anterior uveitis.
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Binocular diplopia
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Epithelial Defect + associated anterior uveitis + hypopyon
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Epithelial Defect+ localized delayed staining.
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Epithelial Defect + Associated anterior uveitis + Hypopyon.
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    corneal epithelium filaments
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    slightly elevated IOP
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    elevated IOP
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    suspected elevated IOP on digital examination to bandage contact lens- caused by steroid medication
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Raised IOP
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Raised IOP to 32mmHg. This is due to steroid treatment. Pressure controlled with topicalantiglaucoma
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Partial Conjuctivalization
         subjects affected / exposed
    3 / 27 (11.11%)
         occurrences all number
    3
    metastatic lashes causing epitheliopathy
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    4
    leakage of aquous fluid from central corneal bullae
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Sharp pain. One off. To be expected after this surgery
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    scleral perforation at time of corneal transplantation
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    difficult to identify the explant on the recipient eye. Initially due to local haemorrhage
    Additional description: difficult to identify the explant on the recipient eye. Initially due to local haemorrhage, now that the blood has resolved, the explant is not definitely visible, although it may be incorporate near a blood vessel.
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Corneal Ulcer
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Filamentary Keratites
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Slow siedel positive corneal leak at site of previous lamellar graft wound.
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Poked self in the eye and dislodge the contact lenses
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    bleeding/oozing from the eye 2 days post- transplant
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Elevated Intra Ocular Pressure
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Bandage Contact Lenses fall out
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Dellen formation inside PKP
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Irritation/Foreign body sensation
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Raised IOP digitally
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Bandage contact lens fell out. Patient replaced it himself.
         subjects affected / exposed
    2 / 27 (7.41%)
         occurrences all number
    2
    Perforation of cornea.
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Bandage contact lens fell out. Large epithelial defect.
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Bandage contact lens fell out
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1
    Right pos operative cystoid macula edema
         subjects affected / exposed
    1 / 27 (3.70%)
         occurrences all number
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Jan 2012
    In response to the conditions of favourable opinion specified by REC, the Patient Information Sheet has been amended to include further information on alternative options, if cells do not grow well, and correct REC name. Substantial changes to the study, in response to the MHRA CTA, regarding its duration (to 36 months), and the prohibition of concurrent enrolment of participants in another study.
    11 Sep 2013
    The proposed changes to the protocol were the removal of previous amniotic membrane grafting to the donor eye, as an exclusion criterion; and the amendment to specify that only those patients who have been previously transplanted with ex vivo expanded autologous limbal stem cells being excluded.

    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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