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    Clinical Trial Results:
    An Open-Label Safety Study of Retinal Gene Therapy for Choroideremia with Bilateral, Sequential Administration of Adeno-Associated Viral Vector (AAV2) Encoding Rab Escort Protein 1 (REP1)

    Summary
    EudraCT number
    		 2017-002395-75
    Trial protocol
    		 DE   FR  
    Global end of trial date
    29 Jun 2022

    Results information
    Results version number
    		 v1
    This version publication date
    15 Jul 2023
    First version publication date
    15 Jul 2023
    Other versions
    		 v2

    Trial information

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    Trial identification
    Sponsor protocol code
    273CH203
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03507686
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Protocol number: NSR-REP-02
    Sponsors
    Sponsor organisation name
    Biogen
    Sponsor organisation address
    225 Binney Stretet, Cambridge, United States, 02142
    Public contact
    Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com
    Scientific contact
    Biogen Study Medical Director, Biogen, clinicaltrials@biogen.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
    29 Jun 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Jun 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of the study is to evaluate the safety of bilateral, sequential sub-retinal administration of a single dose of BIIB111 in adult male participants with Choroideremia (CHM).
    Protection of trial subjects
    Written informed consent was obtained from each participant or participant`s legally authorized representative, as applicable, prior to evaluations performed for eligibility. Participants or the participant`s legally authorized representative were given adequate time to review the information in the informed consent/assent and were allowed to ask, and have answered, questions concerning all portions of the conduct of the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Nov 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 50
    Country: Number of subjects enrolled
    Germany: 14
    Country: Number of subjects enrolled
    France: 2
    Worldwide total number of subjects
    66
    EEA total number of subjects
    16
    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)
    64
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants were enrolled at the investigative sites in the France, Germany, and the United States from 29 November 2017 to 29 June 2022.

    Pre-assignment
    Screening details
    		 66 unique male participants with Choroideremia were treated in study. Of which 60 participants were treated in Period 1, 50 participants completed Period 1. 50 participants from Period 1 enrolled in Period 2 along with 6 unique participants who were treated in first eye in previous study (20150371, THOR-TUE-01). 53 participants completed Period 2.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 All Treated Subjects
    Arm description
    		 After vitrectomy and retinal detachment in the study eye 1 and study eye 2, participants received a single administration of BIIB111, 1 * 10^11 genome particles (gp), as a sub-retinal injection on Day 0 (surgery day) of Period 1 and Period 2, respectively.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BIIB111
    Investigational medicinal product code
    Other name
    AAV2-REP1
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intraocular use
    Dosage and administration details
    Administered as specified in the treatment arm.

    Number of subjects in period 1
    		All Treated Subjects
    Started
    66
    Completed
    53
    Not completed
    13
         Adverse event, serious fatal
    1
         Consent withdrawn by subject
    2
         Serious Adverse event
    4
         Site Terminated by Sponsor
    2
         Reason not Specified
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    All Treated Subjects
    Reporting group description
    		 After vitrectomy and retinal detachment in the study eye 1 and study eye 2, participants received a single administration of BIIB111, 1 * 10^11 genome particles (gp), as a sub-retinal injection on Day 0 (surgery day) of Period 1 and Period 2, respectively.

    Reporting group values
    		 All Treated Subjects Total
    Number of subjects
    		 66
    Age Categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 36.7 ( 13.57 ) -
    Gender categorical
    Units: Subjects
        Male
    		 66 66
        Female
    		 0 0
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 4 4
        Not Hispanic or Latino
    		 60 60
        Unknown or Not Reported
    		 2 2
    Race
    Units: Subjects
        Asian
    		 1 1
        White
    		 65 65
    Subject analysis sets

    Subject analysis set title
    Treatment Period 1: BIIB111
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    After vitrectomy and retinal detachment in the study eye 1, participants received a single administration of BIIB111, 1 * 10^11 gp, as a sub-retinal injection on Day 0 (surgery day) of Period 1.

    Subject analysis set title
    Treatment Period 2: BIIB111
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    After vitrectomy and retinal detachment in the study eye 2, participants received a single administration of BIIB111, 1 * 10^11 gp, as a sub-retinal injection on Day 0 (surgery day) of Period 2.

    Subject analysis sets values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects
    60
    56
    Age Categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    0 ( )
    0 ( )
    Gender categorical
    Units: Subjects
        Male
    0
    0
        Female
    0
    0
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    0
    0
        Not Hispanic or Latino
    0
    0
        Unknown or Not Reported
    0
    0
    Race
    Units: Subjects
        Asian
    0
    0
        White
    0
    0

    End points

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    End points reporting groups
    Reporting group title
    All Treated Subjects
    Reporting group description
    		 After vitrectomy and retinal detachment in the study eye 1 and study eye 2, participants received a single administration of BIIB111, 1 * 10^11 genome particles (gp), as a sub-retinal injection on Day 0 (surgery day) of Period 1 and Period 2, respectively.

    Subject analysis set title
    Treatment Period 1: BIIB111
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    After vitrectomy and retinal detachment in the study eye 1, participants received a single administration of BIIB111, 1 * 10^11 gp, as a sub-retinal injection on Day 0 (surgery day) of Period 1.

    Subject analysis set title
    Treatment Period 2: BIIB111
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    After vitrectomy and retinal detachment in the study eye 2, participants received a single administration of BIIB111, 1 * 10^11 gp, as a sub-retinal injection on Day 0 (surgery day) of Period 2.

    Primary: Mean Best-Corrected Visual Acuity (BCVA) as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart in Letters at Month 12

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    End point title
    		 Mean Best-Corrected Visual Acuity (BCVA) as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart in Letters at Month 12 [1]
    End point description
    BCVA was assessed for both eyes using the ETDRS visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eyes. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of Subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Primary
    End point timeframe
    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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    53
    Units: letters
    arithmetic mean (standard deviation)
        Study Eye 1
    68.0 ( 25.18 )
    76.5 ( 13.78 )
        Study Eye 2
    82.3 ( 8.67 )
    81.2 ( 10.82 )
    No statistical analyses for this end point

    Primary: Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Slit Lamp Examination

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    End point title
    		 Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Slit Lamp Examination [2]
    End point description
    Slit lamp examinations of study eyes included examination of Cornea, Conjunctiva, Iris, Lens, and Anterior Segment. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified category at specified timepoint.
    End point type
    Primary
    End point timeframe
    Baseline, Month 12
    Notes
    [2] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    60
    56
    Units: participants
        Cornea: Study Eye 1: Baseline
    0
    0
        Cornea: Study Eye 1: Month 12 (n=15,53)
    0
    0
        Cornea: Study Eye 2: Baseline
    0
    0
        Cornea: Study Eye 2: Month 12 (n=15,53)
    0
    0
        Conjunctiva: Study Eye 1: Baseline
    0
    1
        Conjunctiva: Study Eye 1: Month 12 (n=15,53)
    0
    0
        Conjunctiva: Study Eye 2: Baseline
    0
    0
        Conjunctiva: Study Eye 2: Month 12 (n=15,53)
    0
    0
        Iris: Study Eye 1: Baseline
    0
    0
        Iris: Study Eye 1: Month 12 (n=15,53)
    0
    0
        Iris: Study Eye 2: Baseline
    0
    0
        Iris: Study Eye 2: Month 12 (n=15,53)
    0
    0
        Lens: Study Eye 1: Baseline
    2
    2
        Lens: Study Eye 1: Month 12 (n=15,53)
    1
    4
        Lens: Study Eye 2: Baseline
    2
    2
        Lens: Study Eye 2: Month 12 (n=15,53)
    0
    3
        Anterior Segment: Study Eye 1: Baseline
    0
    0
        Anterior Segment: Study Eye 1: Month 12 (n=15,53)
    0
    0
        Anterior Segment: Study Eye 2: Baseline
    0
    0
        Anterior Segment: Study Eye 2: Month 12 (n=15,53)
    0
    0
    No statistical analyses for this end point

    Primary: Ophthalmic Examination Assessment: Mean Intraocular Pressure (IOP) at Month 12

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    End point title
    		 Ophthalmic Examination Assessment: Mean Intraocular Pressure (IOP) at Month 12 [3]
    End point description
    IOP, the fluid pressure inside the eye was measured and reported in mmHg. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Primary
    End point timeframe
    Month 12
    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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    52
    Units: millimetres mercury (mmHg)
    arithmetic mean (standard deviation)
        Study Eye 1
    13.5 ( 3.09 )
    13.5 ( 3.12 )
        Study Eye 2
    14.9 ( 2.50 )
    13.5 ( 3.55 )
    No statistical analyses for this end point

    Primary: Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Dilated Ophthalmoscopy

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    End point title
    		 Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Dilated Ophthalmoscopy [4]
    End point description
    Dilated Ophthalmoscopy examination of study eyes included examination of Vitreous, Macula, Peripheral retina, Choroid, and Optic nerve. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified category at specified timepoint.
    End point type
    Primary
    End point timeframe
    Baseline, Month 12
    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: No statistical analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    60
    56
    Units: participants
        Vitreous: Study Eye 1: Baseline
    0
    0
        Vitreous: Study Eye 1: Month 12 (n=15,53)
    1
    1
        Vitreous: Study Eye 2: Baseline
    0
    0
        Vitreous: Study Eye 2: Month 12 (n=15,53)
    0
    1
        Macula: Study Eye 1: Baseline
    57
    54
        Macula: Study Eye 1: Month 12 (n=15,53)
    15
    51
        Macula: Study Eye 2: Baseline
    58
    54
        Macula: Study Eye 2: Month 12 (n=15,53)
    15
    51
        Peripheral Retina: Study Eye 1: Baseline
    58
    54
        Peripheral Retina: Study Eye 1:Month 12 (n=15,53)
    15
    51
        Peripheral Retina: Study Eye 2: Baseline
    58
    54
        Peripheral Retina: Study Eye 2:Month 12 (n=15,53)
    15
    51
        Choroid: Study Eye 1: Baseline
    58
    54
        Choroid: Study Eye 1: Month 12 (n=15,53)
    15
    51
        Choroid: Study Eye 2: Baseline
    58
    54
        Choroid: Study Eye 2: Month 12 (n=15,53)
    15
    51
        Optic Nerve: Study Eye 1: Baseline
    5
    4
        Optic Nerve: Study Eye 1: Month 12 (n=15,53)
    0
    3
        Optic Nerve: Study Eye 2: Baseline
    6
    4
        Optic Nerve: Study Eye 2: Month 12 (n=15,53)
    0
    4
    No statistical analyses for this end point

    Primary: Ophthalmic Examination Assessment: Number of Participants With Lens Opacity Grading

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    End point title
    		 Ophthalmic Examination Assessment: Number of Participants With Lens Opacity Grading [5]
    End point description
    The following lens opacity grades are reported for categories 1-4: Nuclear Opalescence grade, Nuclear Color grade, Cortical Cataract grade, and Posterior Cataract grade. Category 1 includes values 1, 1.0 and 0.x, Category 2 includes values 2, 2.0 and 1.x, Category 3 includes values 3, 3.0 and 2.x, and Category 4 includes values 4, 4.0, 3.x and any values above 4. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified category of specified parameter.
    End point type
    Primary
    End point timeframe
    Month 12
    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: No statistical analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    50
    Units: participants
        NuclearOpalescenceGrade:Category1:Eye1(n=14,50)
    13
    38
        NuclearOpalescenceGrade:Category 2:Eye1(n=14,50)
    1
    8
        NuclearOpalescenceGrade:Category 3:Eye1(n=14,50)
    0
    4
        NuclearOpalescenceGrade: Category 4:Eye1(N=14,50)
    0
    0
        Nuclear Opalescence Grade: Category 1: Study Eye 2
    14
    38
        Nuclear Opalescence Grade: Category 2: Study Eye 2
    1
    10
        Nuclear Opalescence Grade: Category 3: Study Eye 2
    0
    2
        Nuclear Opalescence Grade: Category 4: Study Eye 2
    0
    0
        Nuclear Color Grade:Category 1:Study Eye1(n=14,50)
    14
    41
        Nuclear Color Grade:Category 2:Study Eye1(n=14,50)
    0
    5
        Nuclear Color Grade:Category 3:Study Eye1(n=14,50)
    0
    4
        NuclearColorGrade:Category 4:Study Eye 1 (n=14,50)
    0
    0
        Nuclear Color Grade: Category 1: Study Eye 2
    15
    41
        Nuclear Color Grade: Category 2: Study Eye 2
    0
    7
        Nuclear Color Grade: Category 3: Study Eye 2
    0
    2
        Nuclear Color Grade: Category 4: Study Eye 2
    0
    0
        Cortical CataractGrade:Category1:Eye1(n=14,50)
    13
    43
        Cortical CataractGrade:Category2:Eye1(n=14,50)
    1
    5
        Cortical CataractGrade:Category3:Eye1(n=14,50)
    0
    2
        Cortical CataractGrade:Category4:Eye1(n=14,50)
    0
    0
        Cortical Cataract Grade: Category 1: Study Eye 2
    14
    44
        Cortical Cataract Grade: Category 2: Study Eye 2
    1
    6
        Cortical Cataract Grade: Category 3: Study Eye 2
    0
    0
        Cortical Cataract Grade: Category 4: Study Eye 2
    0
    0
        PosteriorCataractGrade:Category1:Eye1(n=14,50)
    13
    40
        PosteriorCataractGrade:Category2:Eye1(n=14,50)
    0
    6
        PosteriorCataractGrade:Category3:Eye1(n=14,50)
    0
    3
        PosteriorCataractGrade:Category4:Eye1(n=14,50)
    1
    1
        Posterior Cataract Grade: Category 1: Study Eye 2
    15
    44
        Posterior Cataract Grade: Category 2: Study Eye 2
    0
    6
        Posterior Cataract Grade: Category 3: Study Eye 2
    0
    0
        Posterior Cataract Grade: Category 4: Study Eye 2
    0
    0
    No statistical analyses for this end point

    Primary: Spectral Domain Optical Coherence Tomography (SD-OCT): Foveal Subfield Thickness at Month 12

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    End point title
    		 Spectral Domain Optical Coherence Tomography (SD-OCT): Foveal Subfield Thickness at Month 12 [6]
    End point description
    SD-OCT was used to assess change in foveal subfield thickness. The measurements were taken after dilation of the participant’s pupil. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Primary
    End point timeframe
    Month 12
    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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    53
    Units: microns (µ)
    arithmetic mean (standard deviation)
        Study Eye 1
    290.7 ( 69.94 )
    258.0 ( 58.20 )
        Study Eye 2
    283.8 ( 46.65 )
    270.9 ( 51.66 )
    No statistical analyses for this end point

    Primary: SD-OCT: Total Macular Volume at Month 12

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    End point title
    		 SD-OCT: Total Macular Volume at Month 12 [7]
    End point description
    SD-OCT was used to assess change in total macular volume. The measurements were taken after dilation of the participant’s pupil. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [7] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    53
    Units: cubic millimetres (mm^3)
    arithmetic mean (standard deviation)
        Study Eye 1 (n=14, 53)
    6.770 ( 1.1384 )
    6.638 ( 1.0934 )
        Study Eye 2
    6.903 ( 1.0875 )
    6.741 ( 1.1616 )
    No statistical analyses for this end point

    Primary: SD-OCT: Central Ellipsoid Area at Month 12

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    End point title
    		 SD-OCT: Central Ellipsoid Area at Month 12 [8]
    End point description
    SD-OCT was used to assess change in central ellipsoid area. The measurements were taken after dilation of the participant’s pupil. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [8] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    8
    28
    Units: square millimetres (mm^2)
    arithmetic mean (standard deviation)
        Study Eye 1 (n=7, 25)
    3.213 ( 2.1098 )
    2.971 ( 1.7374 )
        Study Eye 2
    4.404 ( 2.2848 )
    3.810 ( 2.5563 )
    No statistical analyses for this end point

    Primary: SD-OCT: Central Horizontal Ellipsoid Width at Month 12

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    End point title
    		 SD-OCT: Central Horizontal Ellipsoid Width at Month 12 [9]
    End point description
    SD-OCT was used to assess change in central horizontal ellipsoid width. The measurements were taken after dilation of the participant`s pupil. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [9] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    14
    47
    Units: microns
    arithmetic mean (standard deviation)
        Study Eye 1 (n=12, 45)
    2346.0 ( 1511.67 )
    1951.2 ( 1223.26 )
        Study Eye 2
    2230.2 ( 1122.89 )
    1950.1 ( 1188.74 )
    No statistical analyses for this end point

    Primary: SD-OCT: Square Root of Central Ellipsoid Area at Month 12

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    End point title
    		 SD-OCT: Square Root of Central Ellipsoid Area at Month 12 [10]
    End point description
    SD-OCT was used to assess change in square root of central ellipsoid area. The measurements were taken after dilation of the participant’s pupil. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [10] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    8
    28
    Units: mm
    arithmetic mean (standard deviation)
        Study Eye 1 (n=7, 25)
    1.6980 ( 0.62031 )
    1.6346 ( 0.55842 )
        Study Eye 2
    2.0331 ( 0.55575 )
    1.8468 ( 0.64385 )
    No statistical analyses for this end point

    Primary: SD-OCT: Choroidal Thickness at Foveal Center at Month 12

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    End point title
    		 SD-OCT: Choroidal Thickness at Foveal Center at Month 12 [11]
    End point description
    SD-OCT was used to assess change in choroidal thickness. The measurements were taken after dilation of the participant`s pupil. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [11] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    52
    Units: microns
    arithmetic mean (standard deviation)
        Study Eye 1
    185.5 ( 81.72 )
    174.2 ( 85.33 )
        Study Eye 2
    207.6 ( 85.89 )
    190.2 ( 87.40 )
    No statistical analyses for this end point

    Primary: Fundus Autofluorescence (AF): Mean Total Area of Preserved Autofluorescence at Month 12

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    End point title
    		 Fundus Autofluorescence (AF): Mean Total Area of Preserved Autofluorescence at Month 12 [12]
    End point description
    AF was used to assess change in total area of preserved autofluoroscence. Here, negative values indicate decline in total area of preserved autofluoroscence. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified parameter.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [12] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    50
    Units: mm^2
    arithmetic mean (standard deviation)
        Study Eye 1 (n=13, 50)
    7.130 ( 6.2326 )
    8.682 ( 9.8972 )
        Study Eye 2 (n=15, 49)
    8.157 ( 7.4969 )
    9.682 ( 11.0688 )
    No statistical analyses for this end point

    Primary: AF: Mean Square Root of Total Area of Preserved AF at Month 12

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    End point title
    		 AF: Mean Square Root of Total Area of Preserved AF at Month 12 [13]
    End point description
    AF was used to assess change in square root of total area of preserved AF. Here, negative values indicate decline in total area of preserved autofluoroscence. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [13] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    50
    Units: mm
    arithmetic mean (standard deviation)
        Study Eye 1 (n=13, 50)
    2.4358 ( 1.13836 )
    2.6149 ( 1.37197 )
        Study Eye 2 (n=15, 49)
    2.6214 ( 1.17348 )
    2.7550 ( 1.46149 )
    No statistical analyses for this end point

    Primary: AF: Mean Distance From Foveal Center to Nearest Border of Preserved AF at Month 12

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    End point title
    		 AF: Mean Distance From Foveal Center to Nearest Border of Preserved AF at Month 12 [14]
    End point description
    Fundus Autofluoroscence was used to assess change in distance from foveal center to nearest border of preserved autofluoroscence. Here, negative values indicate decline in total area of preserved autofluoroscence. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [14] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    53
    Units: mm
    arithmetic mean (standard deviation)
        Study Eye 1
    423.133 ( 559.1529 )
    370.245 ( 733.1618 )
        Study Eye 2 (n=15, 52)
    539.600 ( 602.6063 )
    525.212 ( 688.7141 )
    No statistical analyses for this end point

    Primary: Fundus Photography: Number of Participants With Retinal Pigment Epithelium (RPE) Hyperplasia as per Severity

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    End point title
    		 Fundus Photography: Number of Participants With Retinal Pigment Epithelium (RPE) Hyperplasia as per Severity [15]
    End point description
    Number of participants with RPE hyperplasia are reported for severity grades: mild, moderate, severe. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [15] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    49
    Units: participants
        Mild: Study Eye 1
    7
    26
        Mild: Study Eye 2 (n=15, 48)
    9
    23
        Moderate: Study Eye 1
    8
    21
        Moderate: Study Eye 2 (n=15, 48)
    6
    23
        Severe: Study Eye 1
    0
    2
        Severe: Study Eye 2 (n=15, 48)
    0
    2
    No statistical analyses for this end point

    Primary: Fundus Photography: Number of Participants With Retinal Arteriolar Narrowing as per Severity

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    End point title
    		 Fundus Photography: Number of Participants With Retinal Arteriolar Narrowing as per Severity [16]
    End point description
    Number of participants with retinal arteriolar narrowing are reported for severity grades: mild, moderate, severe. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [16] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    50
    Units: participants
        Mild: Study Eye 1
    13
    37
        Mild: Study Eye 2 (n=15, 49)
    12
    36
        Moderate: Study Eye 1
    1
    10
        Moderate: Study Eye 2 (n=15, 49)
    2
    10
        Severe: Study Eye 1
    0
    0
        Severe: Study Eye 2 (n=15, 49)
    0
    0
    No statistical analyses for this end point

    Primary: Fundus Photography: Number of Participants With Optic Atrophy/Pallor as per Severity

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    End point title
    		 Fundus Photography: Number of Participants With Optic Atrophy/Pallor as per Severity [17]
    End point description
    Number of participants with optic atrophy/pallor are reported for severity grades: mild, moderate, severe. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [17] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    50
    Units: participants
        Mild: Study Eye 1
    0
    0
        Mild: Study Eye 2 (n=15, 49)
    0
    0
        Moderate: Study Eye 1
    0
    0
        Moderate: Study Eye 2 (n=15, 49)
    0
    0
        Severe: Study Eye 1
    0
    0
        Severe: Study Eye 2 (n=15, 49)
    0
    0
    No statistical analyses for this end point

    Primary: Fundus Photography: Number of Participants With Retinal Vessel Sheathing as per Severity

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    End point title
    		 Fundus Photography: Number of Participants With Retinal Vessel Sheathing as per Severity [18]
    End point description
    Number of participants with retinal vessel sheathing are reported for severity grades: mild, moderate, severe. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [18] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    49
    Units: participants
        Mild: Study Eye 1
    0
    0
        Mild: Study Eye 2 (n=15, 48)
    0
    0
        Moderate: Study Eye 1
    0
    0
        Moderate: Study Eye 2 (n-15, 48)
    0
    0
        Severe: Study Eye 1
    0
    0
        Severe: Study Eye 2 (n=15, 48)
    0
    0
    No statistical analyses for this end point

    Primary: Fundus Photography: Number of Participants With Optic Disc Swelling as per Severity

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    End point title
    		 Fundus Photography: Number of Participants With Optic Disc Swelling as per Severity [19]
    End point description
    Number of participants with optic disc swelling are reported for severity grades: mild, moderate, severe. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [19] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    50
    Units: participants
        Mild: Study Eye 1
    0
    1
        Mild: Study Eye 2 (n=15, 49)
    0
    0
        Moderate: Study Eye 1
    0
    0
        Moderate: Study Eye 2 (n=15, 49)
    0
    0
        Severe: Study Eye 1
    0
    0
        Severe: Study Eye 2 (n=15, 49)
    0
    0
    No statistical analyses for this end point

    Primary: Microperimetry: Retinal Mean Sensitivity at Month 12

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    End point title
    		 Microperimetry: Retinal Mean Sensitivity at Month 12 [20]
    End point description
    Microperimetry was conducted to assess retinal mean sensitivity within the macula. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [20] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    53
    Units: decibels (dB)
    arithmetic mean (standard deviation)
        Study Eye 1
    4.05 ( 4.565 )
    5.93 ( 6.991 )
        Study Eye 2
    5.41 ( 5.239 )
    6.37 ( 6.720 )
    No statistical analyses for this end point

    Primary: Microperimetry: Bivariate Contour Ellipse Area 63% at Month 12

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    End point title
    		 Microperimetry: Bivariate Contour Ellipse Area 63% at Month 12 [21]
    End point description
    Microperimetry was conducted to assess bivariate contour ellipse area 63%. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. 'Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [21] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    53
    Units: square degrees (deg^2)
    arithmetic mean (standard deviation)
        Study Eye 1
    7.91 ( 13.287 )
    2.09 ( 4.701 )
        Study Eye 2
    1.45 ( 1.874 )
    1.92 ( 5.510 )
    No statistical analyses for this end point

    Primary: Microperimetry: Fixation Losses (in Percentage) at Month 12

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    End point title
    		 Microperimetry: Fixation Losses (in Percentage) at Month 12 [22]
    End point description
    Microperimetry was conducted to assess change in fixation losses (in percentage). All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [22] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    5
    23
    Units: percentage (%)
    arithmetic mean (standard deviation)
        Study Eye 1
    9.0 ( 12.45 )
    2.2 ( 7.20 )
        Study Eye 2
    4.0 ( 8.94 )
    5.0 ( 9.17 )
    No statistical analyses for this end point

    Primary: Microperimetry: Bivariate Contour Ellipse Area 95% at Month 12

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    End point title
    		 Microperimetry: Bivariate Contour Ellipse Area 95% at Month 12 [23]
    End point description
    Microperimetry was conducted to assess bivariate contour ellipse area 95%. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [23] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    53
    Units: deg^2
    arithmetic mean (standard deviation)
        Study Eye 1
    23.69 ( 39.857 )
    6.27 ( 14.106 )
        Study Eye 2
    4.35 ( 5.624 )
    5.76 ( 16.518 )
    No statistical analyses for this end point

    Primary: Percentage of Participants With at Least one Treatment-Emergent Adverse Event (TEAE)

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    End point title
    		 Percentage of Participants With at Least one Treatment-Emergent Adverse Event (TEAE) [24]
    End point description
    An AE is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug/surgical procedure, whether or not related to the investigational product or with the surgical procedure. TEAEs are defined as AEs starting on or after the day of the first surgery. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. The AEs data were collected and reported for unique participants instead of period-wise treated population.
    End point type
    Primary
    End point timeframe
    Day 0 (surgery) in period 1 up to last follow up visit in period 2 (approximately 2 years)
    Notes
    [24] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    60
    56
    Units: percentage of participants
        number (not applicable)
    100
    96.4
    No statistical analyses for this end point

    Primary: Number of Participants With Vector Shedding Post-treatment at Month 3

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    End point title
    		 Number of Participants With Vector Shedding Post-treatment at Month 3 [25]
    End point description
    Tears (for both eyes- oculus dexter [OD] and oculus sinister [OS]), blood, urine and saliva samples were collected and tested using an appropriate assay for evidence of vector shedding. Participants with positive result for vector shredding post treatment are reported. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified parameter.
    End point type
    Primary
    End point timeframe
    Baseline, at Month 3
    Notes
    [25] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    48
    56
    Units: participants
        Tears OD (n=47, 54)
    0
    0
        Tears OS (n=48, 55)
    0
    0
        Blood (n=47, 55)
    0
    0
        Saliva (n=48, 54)
    0
    0
        Urine (n=47, 56)
    0
    0
    No statistical analyses for this end point

    Primary: Number of Participants With Anti-drug Antibodies Post-treatment at Month 12

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    End point title
    		 Number of Participants With Anti-drug Antibodies Post-treatment at Month 12 [26]
    End point description
    Participants with antibodies to the REP-1 transgenic product are reported. The immunogenicity analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2 with baseline sample and at least one post-surgery sample evaluable for immunogenicity.
    End point type
    Primary
    End point timeframe
    Month 12
    Notes
    [26] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    60
    56
    Units: participants
    0
    0
    No statistical analyses for this end point

    Primary: Vital Signs: Change From Baseline in Blood Pressure at Month 12

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    End point title
    		 Vital Signs: Change From Baseline in Blood Pressure at Month 12 [27]
    End point description
    Change from baseline in Systolic and diastolic blood pressures (SBP and DBP) [mmHg] were reported. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis at specified timepoint.
    End point type
    Primary
    End point timeframe
    Baseline, Month 12
    Notes
    [27] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    60
    22
    Units: mmHg
    arithmetic mean (standard deviation)
        Systolic BP (SBP): Baseline
    122.3 ( 14.73 )
    125.4 ( 11.52 )
        SBP: Change at Month 12 (n=14, 22)
    -7.2 ( 16.12 )
    -2.0 ( 10.65 )
        Diastolic BP (DBP): Baseline
    78.3 ( 9.56 )
    80.5 ( 6.91 )
        DBP: Change at Month 12 (n=14, 22)
    -1.0 ( 11.29 )
    -1.9 ( 9.60 )
    No statistical analyses for this end point

    Primary: Vital Signs: Change From Baseline in Pulse Rate at Month 12

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    End point title
    		 Vital Signs: Change From Baseline in Pulse Rate at Month 12 [28]
    End point description
    Change from baseline in pulse rate (beats per minute) were reported. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis at specified timepoint.
    End point type
    Primary
    End point timeframe
    Baseline, Month 12
    Notes
    [28] - 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 analysis was planned or performed for this endpoint.
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    60
    22
    Units: beats per minute
    arithmetic mean (standard deviation)
        Baseline
    69.8 ( 13.31 )
    71.5 ( 10.91 )
        Change at Month 12 (n=14, 22)
    6.7 ( 16.41 )
    0.9 ( 10.46 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in BCVA as Measured by the ETDRS Chart

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    End point title
    		 Change From Baseline in BCVA as Measured by the ETDRS Chart
    End point description
    BCVA was assessed for both eyes using the ETDRS VA chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eyes. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). An increase in the number of letters read correctly means that vision has improved. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    53
    Units: letters
    arithmetic mean (standard deviation)
        Change at Month 12: Study Eye 1
    -8.6 ( 24.55 )
    -1.3 ( 7.77 )
        Change at Month 12: Study Eye 2
    2.2 ( 2.93 )
    -2.2 ( 8.27 )
    No statistical analyses for this end point

    Secondary: AF: Change From Baseline in Square Root of Total Area of Preserved AF at Month 12

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    End point title
    		 AF: Change From Baseline in Square Root of Total Area of Preserved AF at Month 12
    End point description
    AF was used to assess change in square root of total area of preserved AF. Here negative values indicate decline in total area of preserved autofluoroscence. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    50
    Units: mm
    arithmetic mean (standard deviation)
        Change at Month 12: Study Eye1 (n=13,50)
    -0.1981 ( 0.13033 )
    -0.2197 ( 0.18111 )
        Change at Month 12: Study Eye2 (n=15,49)
    -0.1345 ( 0.04362 )
    -0.1736 ( 0.16090 )
    No statistical analyses for this end point

    Secondary: AF: Change From Baseline in Total Area of Preserved Autofluorescence at Month 12

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    End point title
    		 AF: Change From Baseline in Total Area of Preserved Autofluorescence at Month 12
    End point description
    AF was used to assess change in total area of preserved autofluoroscence. Here negative values indicate decline in total area of preserved autofluoroscence. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. Number of subjects analysed’ indicates the number of subjects with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    50
    Units: mm^2
    arithmetic mean (standard deviation)
        Change at Month 12: Study Eye 1 (n=13,50)
    -1.158 ( 1.3362 )
    -1.502 ( 1.9315 )
        Change at Month 12: Study Eye 2 (n=15,49)
    -0.772 ( 0.5381 )
    -1.313 ( 1.9967 )
    No statistical analyses for this end point

    Secondary: AF: Change From Baseline in Distance From Foveal Center to Nearest Border of Preserved AF at Month 12

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    End point title
    		 AF: Change From Baseline in Distance From Foveal Center to Nearest Border of Preserved AF at Month 12
    End point description
    Fundus Autofluoroscence was used to assess change in distance from foveal center to nearest border of preserved autofluoroscence. Here negative values indicate decline in total area of preserved autofluoroscence. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    53
    Units: mm
    arithmetic mean (standard deviation)
        Change at Month 12: Study Eye 1
    -160.000 ( 197.9094 )
    -94.321 ( 106.4964 )
        Change at Month 12: Study Eye 2 (n=15,52)
    -76.000 ( 71.9107 )
    -80.596 ( 135.5793 )
    No statistical analyses for this end point

    Secondary: SD-OCT: Change From Baseline in Foveal Subfield Thickness at Month 12

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    End point title
    		 SD-OCT: Change From Baseline in Foveal Subfield Thickness at Month 12
    End point description
    SD-OCT was used to assess change in foveal subfield thickness. The measurements were taken after dilation of the participant’s pupil. A negative change from baseline indicates decline in foveal subfield thickness. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    53
    Units: microns
    arithmetic mean (standard deviation)
        Change at Month 12: Study Eye 1
    1.7 ( 53.08 )
    -2.9 ( 12.02 )
        Change at Month 12: Study Eye 2
    -3.5 ( 7.40 )
    -5.7 ( 23.96 )
    No statistical analyses for this end point

    Secondary: SD-OCT: Change From Baseline in the Central Horizontal Ellipsoid Width at Month 12

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    End point title
    		 SD-OCT: Change From Baseline in the Central Horizontal Ellipsoid Width at Month 12
    End point description
    SD-OCT was used to assess change in central horizontal ellipsoid width. The measurements were taken after dilation of the participant`s pupil. A negative change from baseline indicates decline in central horizontal ellipsoid width. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    14
    44
    Units: microns
    arithmetic mean (standard deviation)
        Change at Month 12: Study Eye 1 (n=12,44)
    -156.8 ( 185.66 )
    -161.5 ( 299.00 )
        Change at Month 12: Study Eye 2 (n=14,43)
    -217.5 ( 388.56 )
    -150.4 ( 360.87 )
    No statistical analyses for this end point

    Secondary: SD-OCT: Change From Baseline in Total Macular Volume at Month 12

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    End point title
    		 SD-OCT: Change From Baseline in Total Macular Volume at Month 12
    End point description
    SD-OCT was used to assess change in total macular volume. The measurements were taken after dilation of the participant’s pupil. A negative change from baseline indicates decline in total macular volume. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    53
    Units: mm^3
    arithmetic mean (standard deviation)
        Change at Month12:StudyEye1(n=14,53)
    -0.201 ( 0.2275 )
    -0.188 ( 0.1400 )
        Change at Month 12: Study Eye 2
    -0.093 ( 0.1344 )
    -0.233 ( 0.3969 )
    No statistical analyses for this end point

    Secondary: SD-OCT: Change From Baseline in Square Root of Central Ellipsoid Area at Month 12

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    End point title
    		 SD-OCT: Change From Baseline in Square Root of Central Ellipsoid Area at Month 12
    End point description
    SD-OCT was used to assess change in square root of central ellipsoid area. The measurements were taken after dilation of the participant’s pupil. A negative change from baseline indicates decline in square root of central ellipsoid area. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    7
    27
    Units: mm
    arithmetic mean (standard deviation)
        Change at Month 12: Study Eye 1 (n=6,23)
    -0.1348 ( 0.08110 )
    -0.1345 ( 0.06117 )
        Change at Month 12: Study Eye 2
    -0.1121 ( 0.08193 )
    -0.0944 ( 0.09347 )
    No statistical analyses for this end point

    Secondary: SD-OCT: Change From Baseline in Central Ellipsoid Area at Month 12

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    End point title
    		 SD-OCT: Change From Baseline in Central Ellipsoid Area at Month 12
    End point description
    SD-OCT was used to assess change in central ellipsoid area. The measurements were taken after dilation of the participant’s pupil. A negative change from baseline indicates decline in central ellipsoid area. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available for analysis of specified eye.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    7
    27
    Units: mm^2
    arithmetic mean (standard deviation)
        Change at Month 12: Study Eye 1 (n=6,23)
    -0.408 ( 0.2184 )
    -0.452 ( 0.2776 )
        Change at Month 12: Study Eye 2
    -0.466 ( 0.3543 )
    -0.369 ( 0.3425 )
    No statistical analyses for this end point

    Secondary: SD-OCT: Change From Baseline in the Choroidal Thickness at Foveal Center at Month 12

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    End point title
    		 SD-OCT: Change From Baseline in the Choroidal Thickness at Foveal Center at Month 12
    End point description
    SD-OCT was used to assess change in choroidal thickness. The measurements were taken after dilation of the participant`s pupil. A negative change from baseline indicates decline in choroidal thickness. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. 'Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    60
    56
    Units: microns
    arithmetic mean (standard deviation)
        Change at Month 12: Study Eye 1
    -12.9 ( 35.57 )
    -13.7 ( 30.73 )
        Change at Month 12: Study Eye 2
    -9.8 ( 23.73 )
    2.9 ( 23.62 )
    No statistical analyses for this end point

    Secondary: Microperimetry: Change From Baseline in Bivariate Contour Ellipse Area 63% at Month 12

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    End point title
    		 Microperimetry: Change From Baseline in Bivariate Contour Ellipse Area 63% at Month 12
    End point description
    Microperimetry was conducted to assess change in bivariate contour ellipse area 63%. A negative change from baseline indicates decline in bivariate contour ellipse area 63%. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    53
    Units: deg^2
    arithmetic mean (standard deviation)
        Change at Month 12: Study Eye 1
    4.42 ( 14.383 )
    -0.22 ( 6.733 )
        Change at Month 12: Study Eye 2
    -0.02 ( 1.296 )
    0.63 ( 5.681 )
    No statistical analyses for this end point

    Secondary: Microperimetry: Change From Baseline in Mean Retinal Sensitivity at Month 12

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    End point title
    		 Microperimetry: Change From Baseline in Mean Retinal Sensitivity at Month 12
    End point description
    Microperimetry was conducted to assess change in mean retinal sensitivity within the macula. A negative change from baseline indicates decline in retinal sensitivity. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    53
    Units: dB
    arithmetic mean (standard deviation)
        Change at Month 12: Study Eye 1
    -0.79 ( 1.160 )
    -0.38 ( 1.931 )
        Change at Month 12: Study Eye 2
    0.15 ( 0.725 )
    -0.73 ( 1.435 )
    No statistical analyses for this end point

    Secondary: Microperimetry: Change From Baseline in Fixation Losses (in Percentage) at Month 12

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    End point title
    		 Microperimetry: Change From Baseline in Fixation Losses (in Percentage) at Month 12
    End point description
    Microperimetry was conducted to assess change in fixation losses (in percentage). A negative change from baseline indicates decline in fixation losses. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    4
    14
    Units: percentage
    arithmetic mean (standard deviation)
        Change at Month 12: Study Eye 1
    5.3 ( 13.60 )
    -4.5 ( 11.72 )
        Change at Month 12: Study Eye 2
    -6.3 ( 12.50 )
    2.8 ( 7.40 )
    No statistical analyses for this end point

    Secondary: Microperimetry: Change From Baseline in the Bivariate Contour Ellipse Area 95% at Month 12

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    End point title
    		 Microperimetry: Change From Baseline in the Bivariate Contour Ellipse Area 95% at Month 12
    End point description
    Microperimetry was conducted to assess change in bivariate contour ellipse area 95%. A negative change from baseline indicates decline in bivariate contour ellipse area 95%. All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Treatment Period 1: BIIB111 Treatment Period 2: BIIB111
    Number of subjects analysed
    15
    53
    Units: deg^2
    arithmetic mean (standard deviation)
        Change at Month 12: Study Eye 1
    13.23 ( 43.125 )
    -0.66 ( 20.204 )
        Change at Month 12: Study Eye 2
    -0.09 ( 3.866 )
    1.90 ( 17.006 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 0 (surgery) in period 1 up to last follow up visit in period 2 (approximately 2 years)
    Adverse event reporting additional description
    All Treated Subjects analysis set included all participants who completed the ‘Day of Surgery’ visit of Period 1 or 2. The AEs data were collected and reported for unique participants enrolled in the study.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Treatment Period 2: BIIB111
    Reporting group description
    		 After vitrectomy and retinal detachment in the study eye 2, participants received a single administration of BIIB111, 1 * 10^11 gp, as a sub-retinal injection on Day 0 (surgery day) of Period 2.

    Reporting group title
    Treatment Period 1: BIIB111
    Reporting group description
    		 After vitrectomy and retinal detachment in the study eye 1, participants received a single administration of BIIB111, 1 * 10^11 gp, as a sub-retinal injection on Day 0 (surgery day) of Period 1.

    Serious adverse events
    		 Treatment Period 2: BIIB111 Treatment Period 1: BIIB111
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 56 (14.29%)
    12 / 60 (20.00%)
         number of deaths (all causes)
    1
    0
         number of deaths resulting from adverse events
    0
    0
    Eye disorders
    Choroidal neovascularisation
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blindness unilateral
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Noninfective retinitis
         subjects affected / exposed
    0 / 56 (0.00%)
    2 / 60 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visual acuity reduced
         subjects affected / exposed
    6 / 56 (10.71%)
    10 / 60 (16.67%)
         occurrences causally related to treatment / all
    3 / 7
    3 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tractional retinal detachment
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye inflammation
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Macular hole
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal degeneration
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Completed suicide
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Depression
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Treatment Period 2: BIIB111 Treatment Period 1: BIIB111
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    53 / 56 (94.64%)
    59 / 60 (98.33%)
    Investigations
    Intraocular pressure increased
         subjects affected / exposed
    8 / 56 (14.29%)
    6 / 60 (10.00%)
         occurrences all number
    15
    8
    Nervous system disorders
    Headache
         subjects affected / exposed
    7 / 56 (12.50%)
    7 / 60 (11.67%)
         occurrences all number
    8
    10
    Eye disorders
    Eye irritation
         subjects affected / exposed
    9 / 56 (16.07%)
    8 / 60 (13.33%)
         occurrences all number
    9
    9
    Conjunctival hyperaemia
         subjects affected / exposed
    6 / 56 (10.71%)
    11 / 60 (18.33%)
         occurrences all number
    9
    11
    Foreign body sensation in eyes
         subjects affected / exposed
    10 / 56 (17.86%)
    11 / 60 (18.33%)
         occurrences all number
    10
    12
    Eye pain
         subjects affected / exposed
    10 / 56 (17.86%)
    9 / 60 (15.00%)
         occurrences all number
    12
    10
    Anterior chamber cell
         subjects affected / exposed
    32 / 56 (57.14%)
    29 / 60 (48.33%)
         occurrences all number
    37
    35
    Conjunctival haemorrhage
         subjects affected / exposed
    36 / 56 (64.29%)
    38 / 60 (63.33%)
         occurrences all number
    38
    38
    Vitreal cells
         subjects affected / exposed
    4 / 56 (7.14%)
    7 / 60 (11.67%)
         occurrences all number
    4
    8
    Vitritis
         subjects affected / exposed
    8 / 56 (14.29%)
    7 / 60 (11.67%)
         occurrences all number
    17
    10
    Dry eye
         subjects affected / exposed
    6 / 56 (10.71%)
    2 / 60 (3.33%)
         occurrences all number
    10
    3
    Anterior chamber flare
         subjects affected / exposed
    4 / 56 (7.14%)
    5 / 60 (8.33%)
         occurrences all number
    4
    5
    Vision blurred
         subjects affected / exposed
    6 / 56 (10.71%)
    4 / 60 (6.67%)
         occurrences all number
    8
    4
    Conjunctival oedema
         subjects affected / exposed
    3 / 56 (5.36%)
    6 / 60 (10.00%)
         occurrences all number
    3
    6
    Visual impairment
         subjects affected / exposed
    4 / 56 (7.14%)
    9 / 60 (15.00%)
         occurrences all number
    5
    10
    Ocular discomfort
         subjects affected / exposed
    7 / 56 (12.50%)
    3 / 60 (5.00%)
         occurrences all number
    9
    4
    Metamorphopsia
         subjects affected / exposed
    5 / 56 (8.93%)
    2 / 60 (3.33%)
         occurrences all number
    6
    2
    Photopsia
         subjects affected / exposed
    6 / 56 (10.71%)
    1 / 60 (1.67%)
         occurrences all number
    10
    4
    Visual acuity reduced
         subjects affected / exposed
    3 / 56 (5.36%)
    4 / 60 (6.67%)
         occurrences all number
    3
    4
    Cataract
         subjects affected / exposed
    4 / 56 (7.14%)
    1 / 60 (1.67%)
         occurrences all number
    7
    2
    Cystoid macular oedema
         subjects affected / exposed
    4 / 56 (7.14%)
    1 / 60 (1.67%)
         occurrences all number
    5
    2
    Eye pruritus
         subjects affected / exposed
    3 / 56 (5.36%)
    3 / 60 (5.00%)
         occurrences all number
    3
    3
    Subretinal fluid
         subjects affected / exposed
    2 / 56 (3.57%)
    3 / 60 (5.00%)
         occurrences all number
    3
    3
    Vitreous floaters
         subjects affected / exposed
    4 / 56 (7.14%)
    1 / 60 (1.67%)
         occurrences all number
    6
    1
    Eyelid ptosis
         subjects affected / exposed
    4 / 56 (7.14%)
    1 / 60 (1.67%)
         occurrences all number
    4
    1
    Ocular hypertension
         subjects affected / exposed
    2 / 56 (3.57%)
    3 / 60 (5.00%)
         occurrences all number
    2
    4
    Cataract subcapsular
         subjects affected / exposed
    3 / 56 (5.36%)
    1 / 60 (1.67%)
         occurrences all number
    4
    2
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    3 / 56 (5.36%)
    0 / 60 (0.00%)
         occurrences all number
    3
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    6 / 56 (10.71%)
    8 / 60 (13.33%)
         occurrences all number
    6
    9

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 May 2018
    Amendment 1 states: • New text added to clarify time period between surgeries and requirement for an assessment of overall ocular health and function before scheduling of second eye. • Added text to clarify that if the post-operatively severe ocular inflammation is present, the participant would be terminated from the trial, and that any post-operative complication or poor visual outcome prevents the second eye from continuing to surgery. •Details of the vitrectomy procedure have been added for clarification. Emergency contact information has been added. • New Section added for additional safety gating and stopping criteria. Immunogenicity testing has been specified. • Steroid therapy in the perioperative period was clarified for when surgeries are temporally close.
    03 Feb 2019
    Amendment 2 states: • Sample size was increased from 15 to 60. • Specific language was added regarding allocation of 60 participants into 3 surgery windows of varying length, to provide the broadest safety profile available on participants treated with short, medium, and long time periods between surgeries. • Corticosteroid regimen was revised to clarify administration required with bilateral treatment performed with very short windows between surgeries. • Visual acuity inclusion criterion was revised to allow for eligibility of participants with more significant visual impairment. • New inclusion criterion has been added mandating that participants who enter this study from an antecedent study must have biological samples available to complete an adequate immunogenicity profile • Added benefit-risk assessment section to the Introduction, that outlines the expected risks of AAV2-REP1 treatment to include visual acuity loss post-treatment. • Definition of vision loss as a serious adverse event was clarified.
    29 Oct 2019
    Amendment 3 states: • Visit windows was updated for Visit 3 (Day 3 + 2 days, post-operative follow-up visit) and Visit 4 (Day 7 -1/+2 day) to decrease patient burden and minimize weekend post-operative follow-ups. • Additional information was added to better define serious adverse events. • Updated the Reference Safety Information and the Investigator’s Brochure based on the new data derived from the STAR study.
    30 Apr 2020
    Amendment 4 states: • Added text to include study eye selection and eligibility for surgery as defined by the Patient Eligibility Review Committee.
    11 Nov 2020
    Amendment 5 states: • Added the maximum dose of 80 mg daily of corticosteroid to the corticosteroid regimen. Patient Eligibility Review Committee was added to the Synopsis Exclusion Criteria.

    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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