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)
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Summary
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EudraCT number |
2017-002395-75 |
Trial protocol |
DE FR |
Global end of trial date |
29 Jun 2022
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Results information
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Results version number |
v2(current) |
This version publication date |
15 Oct 2023
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First version publication date |
15 Jul 2023
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
273CH203
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03507686 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Protocol number: NSR-REP-02 | ||
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Sponsors
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Sponsor organisation name |
Biogen
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Sponsor organisation address |
225 Binney Stretet, Cambridge, United States, 02142
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Public contact |
Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com
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Scientific contact |
Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Jun 2022
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Jun 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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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).
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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.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Nov 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 50
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Germany: 14
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Worldwide total number of subjects |
66
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EEA total number of subjects |
16
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
64
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were enrolled at the investigative sites in France, Germany, and the United States from 29 November 2017 to 29 June 2022. | ||||||||||||||||||
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Pre-assignment
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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. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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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
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Investigational medicinal product code |
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Other name |
AAV2-REP1
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intraocular use
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Dosage and administration details |
Administered as specified in the treatment arm.
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Baseline characteristics reporting groups
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Reporting group title |
All Treated Subjects
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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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Treatment Period 1: BIIB111
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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.
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Subject analysis set title |
Treatment Period 2: BIIB111
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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.
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End points reporting groups
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Reporting group title |
All Treated Subjects
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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
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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.
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Subject analysis set title |
Treatment Period 2: BIIB111
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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.
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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.
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End point type |
Primary
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End point timeframe |
Month 12
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| 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. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Ophthalmic Examination Assessment: Mean Intraocular Pressure (IOP) at Month 12 [2] | ||||||||||||||||||
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.
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End point type |
Primary
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End point timeframe |
Month 12
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| 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. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Slit Lamp Examination [3] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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.
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End point type |
Primary
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End point timeframe |
Baseline, Month 12
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| 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. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Baseline, Month 12
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| 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. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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, Posterior Cataract grade. Opacification severity is graded on decimal scale, scores can range from 0.1 (no opacity) to 6.9 (maximum opacity) for Nuclear Opalescence and Nuclear Color grades; and scores can range from 0.1 (lens clear) to 5.9 (lens unclear) for the Cortical and Posterior Cataract grades. 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. For each opacification type the higher grading scores indicate greater severity. All Treated Subjects analysis set. ‘Number of subjects analysed’ indicates number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates number of participants with data available for analysis of specified category of specified parameter.
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End point type |
Primary
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End point timeframe |
Month 12
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| 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. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Month 12
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| 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. |
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| No statistical analyses for this end point | |||||||||||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Month 12
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| 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. |
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| No statistical analyses for this end point | |||||||||||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Month 12
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| 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. |
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| No statistical analyses for this end point | |||||||||||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Month 12
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| 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. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
SD-OCT: Choroidal Thickness at Foveal Center at Month 12 [10] | ||||||||||||||||||
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.
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End point type |
Primary
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End point timeframe |
Month 12
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| 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. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
SD-OCT: Square Root of Central Ellipsoid Area at Month 12 [11] | ||||||||||||||||||
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.
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End point type |
Primary
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End point timeframe |
Month 12
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| 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. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
AF: Mean Square Root of Total Area of Preserved AF at Month 12 [12] | ||||||||||||||||||
End point description |
Fundus AF was used to assess the square root of total area of preserved AF. Areas of preserved AF were identified as
well-demarcated regions of relative hyper AF compared with the background areas of surrounding atrophy. 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.
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End point type |
Primary
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End point timeframe |
Month 12
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| 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. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Fundus Autofluorescence (AF): Mean Total Area of Preserved Autofluorescence at Month 12 [13] | ||||||||||||||||||
End point description |
Fundus AF was used to assess the total area of preserved AF. Areas of preserved AF were identified as well-demarcated regions of relative hyper autofluorescence (hyper AF) compared with the background areas of surrounding atrophy. 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.
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End point type |
Primary
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End point timeframe |
Month 12
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| 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. |
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| No statistical analyses for this end point | |||||||||||||||||||
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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 AF was used to assess the distance from foveal center to nearest border of preserved AF. 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.
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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. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
||||||||||||||||||||||||||||
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. |
||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
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. |
||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point title |
Fundus Photography: Number of Participants With Retinal Vessel Sheathing as per Severity [17] | |||||||||||||||||||||||||||
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 [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. |
||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point title |
Fundus Photography: Number of Participants With Optic Atrophy/Pallor as per Severity [18] | |||||||||||||||||||||||||||
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 [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. |
||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
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. |
||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
|||||||||||||||||||
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. Retinal mean sensitivity to light was measured in decibels in multiple spots across the central and peripheral retina (entire visual field). Higher numbers (decibels) indicate higher 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 |
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. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
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. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Microperimetry: Fixation Losses (in Percentage) at Month 12 [22] | ||||||||||||||||||
End point description |
Microperimetry was conducted to assess fixation losses (in percentage) which samples the optic nerve blind spot for positive responses. 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. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
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. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||
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. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||
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. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
||||||||||
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. |
||||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
|||||||||||||||||||||||||
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. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||
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. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
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
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
AF: Change From Baseline in Total Area of Preserved Autofluorescence at Month 12 | ||||||||||||||||||
End point description |
Fundus AF was used to assess change in total area of preserved AF. Areas of preserved AF were identified as welldemarcated
regions of relative hyper autofluorescence (hyper AF) compared with the background areas of surrounding atrophy. 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
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
AF: Change From Baseline in Square Root of Total Area of Preserved AF at Month 12 | ||||||||||||||||||
End point description |
Fundus AF was used to assess change in square root of total area of preserved AF. Areas of preserved AF were identified as well-demarcated regions of relative hyper AF compared with the background areas of surrounding atrophy. 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
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
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
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
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
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
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
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
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
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
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
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
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
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
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
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Microperimetry: Change From Baseline in Retinal Mean Sensitivity at Month 12 | ||||||||||||||||||
End point description |
Microperimetry was conducted to assess change in retinal mean sensitivity within the macula. Retinal mean sensitivity to light was measured in decibels in multiple spots across the central and peripheral retina (entire visual field). Higher numbers (decibels) indicate higher retinal sensitivity. 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
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
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
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
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
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
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) which samples the optic nerve blind spot for positive responses. 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.
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End point type |
Secondary
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End point timeframe |
Baseline, Month 12
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Day 0 (surgery) in period 1 up to last follow up visit in period 2 (approximately 2 years)
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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.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.0
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Reporting groups
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Reporting group title |
Treatment Period 1: BIIB111
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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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment Period 2: BIIB111
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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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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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. |
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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. |
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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. |
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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. |
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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. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
