Trial Outcomes & Findings for Efficacy and Safety of BIIB111 for the Treatment of Choroideremia (NCT NCT03496012)

Last Updated: 2023-12-07

Results Overview

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. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of participants with a ≥15 -letter improvement from baseline in BCVA at Month 12 was reported for both eyes.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

169 participants

Primary outcome timeframe

Month 12

Results posted on

2023-12-07

Participant Flow

Participants were enrolled at the investigative sites in the United States, Germany, Finland, France, the United Kingdom, Canada, Netherlands, and Denmark from 11 December 2017 to 01 December 2020.

A total of 169 unique male participants with Choroideremia were randomized in the study (66 participants in Untreated Control Group; 34 participants in BIIB111 Low Dose group and 69 participants in BIIB111 High Dose group). Of which, 161 participants completed the study.

Participant milestones

Participant milestones
Measure	Untreated Control Group Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 genome particle \[gp\]) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Overall Study STARTED	66	34	69
Overall Study COMPLETED	62	34	65
Overall Study NOT COMPLETED	4	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Untreated Control Group Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 High Dose Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Overall Study Withdrawal by Subject	2	2
Overall Study Adverse Event	0	1
Overall Study Reason Not Specified	2	1

Baseline Characteristics

Efficacy and Safety of BIIB111 for the Treatment of Choroideremia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Untreated Control Group n=65 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=65 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	Total n=164 Participants Total of all reporting groups
Age, Continuous	49.4 years STANDARD_DEVIATION 13.73 • n=93 Participants	49.8 years STANDARD_DEVIATION 12.62 • n=4 Participants	47.5 years STANDARD_DEVIATION 12.91 • n=27 Participants	48.7 years STANDARD_DEVIATION 13.15 • n=483 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Sex: Female, Male Male	65 Participants n=93 Participants	34 Participants n=4 Participants	65 Participants n=27 Participants	164 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants	8 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	51 Participants n=93 Participants	26 Participants n=4 Participants	54 Participants n=27 Participants	131 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=93 Participants	7 Participants n=4 Participants	7 Participants n=27 Participants	25 Participants n=483 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race/Ethnicity, Customized Race · Black or African American	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race/Ethnicity, Customized Race · White	55 Participants n=93 Participants	30 Participants n=4 Participants	59 Participants n=27 Participants	144 Participants n=483 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race/Ethnicity, Customized Race · Not Reported	7 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants	16 Participants n=483 Participants

PRIMARY outcome

Timeframe: Month 12

Population: Intent-to-treat (ITT) population included all randomized participants who received the study treatment (or the phone call for those in the untreated control group) and had at least one post-treatment BCVA measurement.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=62 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=65 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Percentage of Participants With a ≥15 -Letter Improvement From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart Study Eye	0 percentage of participants Interval 0.0 to 5.8	2.9 percentage of participants Interval 0.1 to 15.3	4.6 percentage of participants Interval 1.0 to 12.9
Percentage of Participants With a ≥15 -Letter Improvement From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart Fellow Eye	0 percentage of participants Interval 0.0 to 5.8	0 percentage of participants Interval 0.0 to 10.3	3.1 percentage of participants Interval 0.4 to 10.7

SECONDARY outcome

Timeframe: Baseline, Month 12

BCVA was assessed for study eye 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 was reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. 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. Here negative values indicate decline in BCVA.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=62 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=65 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in BCVA at Month 12 Reported as Letters Measured by the ETDRS Chart in Study Eye	-2.3 letters Interval -5.31 to 0.61	-1.5 letters Interval -5.47 to 2.5	-0.3 letters Interval -3.18 to 2.64

SECONDARY outcome

Timeframe: Month 12

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. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of participants with a ≥10 -letter improvement from baseline in BCVA at Month 12 was reported for both eyes.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=62 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=65 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Percentage of Participants With a ≥10 -Letter Improvement From Baseline in BCVA at Month 12 Measured by the ETDRS Chart Study Eye	1.6 percentage of participants Interval 0.0 to 8.7	17.6 percentage of participants Interval 6.8 to 34.5	13.8 percentage of participants Interval 6.5 to 24.7
Percentage of Participants With a ≥10 -Letter Improvement From Baseline in BCVA at Month 12 Measured by the ETDRS Chart Fellow Eye	0 percentage of participants Interval 0.0 to 5.8	8.8 percentage of participants Interval 1.9 to 23.7	6.2 percentage of participants Interval 1.7 to 15.0

SECONDARY outcome

Timeframe: Month 12

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. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of participants with no decrease or a decrease of \<5 letters from baseline in BCVA at Month 12 was reported for both eyes.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=62 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=65 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Percentage of Participants With No Decrease From Baseline in BCVA or a Decrease From Baseline in BCVA of <5 ETDRS Letters at Month 12 Measured by the EDRS Chart Study Eye	67.7 percentage of participants Interval 54.7 to 79.1	70.6 percentage of participants Interval 52.5 to 84.9	83.1 percentage of participants Interval 71.7 to 91.2
Percentage of Participants With No Decrease From Baseline in BCVA or a Decrease From Baseline in BCVA of <5 ETDRS Letters at Month 12 Measured by the EDRS Chart Fellow Eye	75.8 percentage of participants Interval 63.3 to 85.8	85.3 percentage of participants Interval 68.9 to 95.0	90.8 percentage of participants Interval 81.0 to 96.5

SECONDARY outcome

Timeframe: Baseline, Months 4 and 8

Population: ITT population included all randomized participants who received the study treatment (or the phone call for those in the untreated control group) and had at least one post-treatment BCVA measurement. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at the specified timepoint.

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 was reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in both the study and fellow 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. Here negative values indicate decline in BCVA.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=61 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=65 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in BCVA at Months 4 and 8 Reported as Letters Measured by the ETDRS Chart Change From Baseline at Month 4: Study Eye	0.2 letters Standard Deviation 4.34	-0.4 letters Standard Deviation 14.16	0.6 letters Standard Deviation 11.11
Change From Baseline in BCVA at Months 4 and 8 Reported as Letters Measured by the ETDRS Chart Change From Baseline at Month 4: Fellow Eye	-1.1 letters Standard Deviation 8.45	0.9 letters Standard Deviation 6.67	2.0 letters Standard Deviation 6.63
Change From Baseline in BCVA at Months 4 and 8 Reported as Letters Measured by the ETDRS Chart Change From Baseline at Month 8: Study Eye	-0.8 letters Standard Deviation 4.93	-1.1 letters Standard Deviation 13.13	0.1 letters Standard Deviation 11.71
Change From Baseline in BCVA at Months 4 and 8 Reported as Letters Measured by the ETDRS Chart Change From Baseline at Month 8: Fellow Eye	-0.4 letters Standard Deviation 8.31	1.9 letters Standard Deviation 7.06	1.6 letters Standard Deviation 5.91

SECONDARY outcome

Timeframe: Baseline, Month 12

Fundus AF was used to assess change in 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. A negative change from baseline indicate decline in total area of preserved AF.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=57 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=63 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in Total Area of Preserved Autofluorescence (AF) at Month 12 in Study Eye	-0.3872 square millimeters (mm^2) Standard Error 0.0389	-0.5413 square millimeters (mm^2) Standard Error 0.0501	-0.5136 square millimeters (mm^2) Standard Error 0.0371

SECONDARY outcome

Timeframe: Baseline, Month 12

Fundus AF was used to assess change in distance from foveal center (FC) to nearest border of preserved AF. A negative change from baseline indicate decline in distance from FC to nearest border of AF.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=57 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=63 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in Distance From Foveal Center to Nearest Border of Preserved AF at Month 12 in Study Eye	21.7796 micrometers (µm) Standard Error 9.6234	23.6171 micrometers (µm) Standard Error 12.3765	21.1660 micrometers (µm) Standard Error 9.1863

SECONDARY outcome

Timeframe: Baseline, Month 12

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.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=61 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=64 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in the Foveal Subfield Thickness Using Spectral Domain Optical Coherence Tomography (SD-OCT) at Month 12 in Study Eye	-6.3152 µm Standard Error 2.7779	-19.8654 µm Standard Error 3.6998	-15.7993 µm Standard Error 2.7233

SECONDARY outcome

Timeframe: Baseline, Month 12

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.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=61 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=64 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in the Total Macular Volume Using SD-OCT at Month 12 in Study Eye	-0.0895 cubic millimeters (mm^3) Standard Error 0.0485	-0.2876 cubic millimeters (mm^3) Standard Error 0.0646	-0.2088 cubic millimeters (mm^3) Standard Error 0.0476

SECONDARY outcome

Timeframe: Baseline, Month 12

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.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=59 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=32 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=60 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in the Central Horizontal Ellipsoid Width Using SD-OCT at Month 12 in Study Eye	-81.9178 µm Standard Error 20.6192	-116.3811 µm Standard Error 27.8213	-170.7214 µm Standard Error 20.4062

SECONDARY outcome

Timeframe: Baseline, Month 12

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.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=37 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=18 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=44 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in the Central Ellipsoid Area Using SD-OCT at Month 12 in Study Eye	-0.2382 mm^2 Standard Error 0.0364	-0.4229 mm^2 Standard Error 0.0527	-0.3440 mm^2 Standard Error 0.0332

SECONDARY outcome

Timeframe: Baseline, Month 12

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.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=61 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=64 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in the Choroidal Thickness Using SD-OCT at Month 12 in Study Eye	-5.4897 µm Standard Error 2.1873	-7.9579 µm Standard Error 2.9207	-4.6371 µm Standard Error 2.1446

SECONDARY outcome

Timeframe: Baseline, Month 12

Microperimetry was conducted to assess change in mean retinal sensitivity within the macula. Retinal mean sensitivity to light was measured in decibels (dBs) in multiple spots across the central and peripheral retina (entire visual field). Higher numbers (dBs) indicate higher retinal sensitivity. A negative change from baseline indicates decline in retinal sensitivity.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=58 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=61 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in the Mean Retinal Sensitivity Using Microperimetry at Month 12 in Study Eye	-0.3443 dBs Standard Error 0.1134	-0.2965 dBs Standard Error 0.1478	-0.5015 dBs Standard Error 0.1112

SECONDARY outcome

Timeframe: Baseline, Month 12

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%.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=58 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=61 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in the Bivariate Contour Ellipse Area 63% Using Microperimetry at Month 12 in Study Eye	-3.2161 square degrees (deg^2) Standard Error 1.2623	-3.3771 square degrees (deg^2) Standard Error 1.6405	-2.5555 square degrees (deg^2) Standard Error 1.2403

SECONDARY outcome

Timeframe: Baseline, Month 12

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%.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=58 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=61 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in the Bivariate Contour Ellipse Area 95% Using Microperimetry at Month 12 in Study Eye	-10.1986 deg^2 Standard Error 4.1004	-14.6926 deg^2 Standard Error 5.3134	-11.6863 deg^2 Standard Error 4.0207

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: ITT population included all randomized participants who received study treatment (phone call for untreated control group) and had at least 1 post-treatment BCVA measurement. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.

Change in contrast sensitivity was assessed by Pelli-Robson chart which uses a single large letter size (20/60 optotype), with contrast varying across groups of letters (6 per line), whose contrast varies from high to low. Participants read letters, starting with highest contrast, until they are unable to read 2 or 3 letters in a single group. Each group had three letters of the same contrast level, so there were three trials per contrast level. Score is assigned based on contrast of last group in which 2 or 3 letters were correctly read. Score is a measure of participant's log contrast sensitivity ranging from 0 (no letters read) to 2.25 (all letters read). Total CS score=\[(total letters correct-3) x 0.05\]. A negative change from baseline indicates worsening in contrast sensitivity score.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=60 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=65 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in Contrast Sensitivity Score at Month 12 in Study Eye	-0.0595 score on a scale Standard Error 0.0315	-0.0130 score on a scale Standard Error 0.0417	-0.0386 score on a scale Standard Error 0.0304

SECONDARY outcome

Timeframe: Baseline, Month 12

Colour vision total error scores were assessed by the Farnsworth Munsell 100 Hue Sort Test. Farnsworth Munsell 100 Hue Test requires placing 100 colour palettes in the correct order based upon colour hue. Scores are determined by the frequency and severity of any displacement in the correct order. One error equates to one misplaced hue, by one step or position. An error score of 0 indicates no errors in ordering the hues while error score greater than 500 indicates virtually no color discrimination. A Total Error Score of 0 to 128 could be seen in a normal population.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=51 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=28 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=51 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in Colour Vision Total Error Score at Month 12 in Study Eye	35.0003 score on a scale Standard Error 23.5973	43.5915 score on a scale Standard Error 31.7720	54.3777 score on a scale Standard Error 24.0358

SECONDARY outcome

Timeframe: Baseline, Month 12

The reading speed (words per minute) was calculated using the following formula: \[number of words in the text - number of misread words\] / reading time x 60. The number of misread words and reading time is collected. A negative change from baseline indicates decline in reading speed.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=23 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=12 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=27 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in Reading Speed Test at Month 12 in Study Eye	-149.5590 words per minute Standard Error 10.9857	-122.1333 words per minute Standard Error 14.3276	-127.4706 words per minute Standard Error 9.9110

SECONDARY outcome

Timeframe: Baseline, Month 12

VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A score of 0 represents the worst outcome and 100 represents the best outcome. A negative change from baseline indicates decline in VFQ-25 score.

Outcome measures

Outcome measures
Measure	Untreated Control Group n=58 Participants Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=63 Participants Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Change From Baseline in the 25-Item Visual Function Questionnaire (VFQ-25) Composite Scores at Month 12 in Study Eye	-2.6971 score on a scale Standard Error 1.2786	1.7236 score on a scale Standard Error 1.6624	0.7964 score on a scale Standard Error 1.2308

Adverse Events

Untreated Control Group

Serious events: 10 serious events

Other events: 9 other events

Deaths: 0 deaths

BIIB111 Low Dose

Serious events: 9 serious events

Other events: 30 other events

Deaths: 0 deaths

BIIB111 High Dose

Serious events: 11 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

US Biogen Clinical Trial Center

Biogen

Phone: 866-633-4636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for non-commercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Untreated Control Group n=65 participants at risk Participants received no sham surgery or study medication to allow for a controlled comparison.	BIIB111 Low Dose n=34 participants at risk Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of low dose (1 × 10\^10 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).	BIIB111 High Dose n=65 participants at risk Followed by vitrectomy and retinal detachment in the study eye, participants received a single administration of high dose (1 × 10\^11 gp) BIIB111 (timrepigene emparvovec) as a sub-retinal injection on Day 0 (surgery day).
Cardiac disorders Angina pectoris	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	2.9% 1/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Cardiac disorders Angina unstable	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	1.5% 1/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Cardiac disorders Aortic valve stenosis	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	1.5% 1/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Cardiac disorders Atrial fibrillation	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	1.5% 1/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Cardiac disorders Myocardial infarction	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	2.9% 1/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Eye disorders Cataract	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	2.9% 1/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Eye disorders Heterophoria	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	1.5% 1/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Eye disorders Macular hole	1.5% 1/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	1.5% 1/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Eye disorders Noninfective retinitis	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	1.5% 1/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Eye disorders Retinal artery embolism	1.5% 1/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Eye disorders Retinal vascular occlusion	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	2.9% 1/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Eye disorders Visual acuity reduced	12.3% 8/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	14.7% 5/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	7.7% 5/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Eye disorders Visual impairment	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	1.5% 1/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Hepatobiliary disorders Cholelithiasis	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	1.5% 1/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Renal and urinary disorders Ureterolithiasis	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	2.9% 1/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Musculoskeletal and connective tissue disorders Arthralgia	1.5% 1/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Infections and infestations Covid-19 pneumonia	1.5% 1/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Infections and infestations Diverticulitis	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	2.9% 1/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Infections and infestations Gastroenteritis	1.5% 1/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Infections and infestations Pilonidal cyst	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	2.9% 1/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).
Infections and infestations Sepsis	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	2.9% 1/34 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).	0.00% 0/65 • From signing of informed consent through end of study (up to 12 months) Safety population included all randomized participants who either received study treatment (BIIB111) or a post-randomization study visit (control group).