A Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using BIIB112

Biogen50 enrolled

Overview

The objective of the study is to evaluate the safety, tolerability and efficacy of a single sub-retinal injection of BIIB112 in participants with X-linked retinitis pigmentosa (XLRP).

This study was previously posted by NightstaRx Ltd. In October 2020, sponsorship of the trial was transferred to Biogen.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

X-Linked Retinitis Pigmentosa

Interventions

BIIB112BIOLOGICAL

Administered as specified in the treatment arm.

Eligibility

Sex: MALEMin age: 10 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: Part 1: * Participants with genetically confirmed diagnosis of XLRP (with RPGR mutation). * Participant with active disease clinically visible within the macular region in both eyes. Part 2: \- Participant with mean total retinal sensitivity in the study eye as assessed by microperimetry ≥ 0.1 dB and ≤8 dB. Key exclusion Criteria: Parts 1 and 2: * Participant with history of amblyopia in either eye. * Participated in a gene therapy trial previously or a clinical trial with an investigational drug in the past 12 weeks or received a gene/cell-based therapy at any time previously. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (8)

Research Site

Gainesville, Florida, United States

Research Site

Miami, Florida, United States

Research Site

Portland, Oregon, United States

Research Site

Philadelphia, Pennsylvania, United States

Outcomes

Primary Outcomes

Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs)

DLTs are defined as any of the following events considered to be related to study drug: Sustained decrease in best-corrected visual acuity (BCVA) of ≥30 letters on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart compared to baseline (sustained is defined as lasting 48 hours or more until recovery, with recovery defined as visual acuity (VA) returning to within 10 letters of baseline VA. An exception is made for surgery-related events occurring in close temporal association {within \<24 hours} of the surgery); Vitreous inflammation, vitritis (\>Grade 3 using standardized Nussenblatt vitreous inflammation scale grading); Any clinically significant retinal damage observed that is not directly attributed to complications of surgery; Any clinically relevant suspected unexpected serious adverse reaction, with the exception of vision loss or vision threatening.

Time frame: Up to Month 24

Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs are defined as the AEs starting or worsening on or after the day of the first surgery.

Time frame: Day 0 (surgery) in Part 1 of the study up to 24 months

Part 2: Percentage of Study Eyes With ≥7 Decibels (dB) Improvement From Baseline at ≥5 Points Out of the 16 Central Loci Points of the 10-2 Grid Assessed by Macular Integrity Assessment (MAIA) Microperimetry

MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '\< 0', '0', or a positive integer. The point labelled as '\< 0' was assigned a value of '-1' by MAIA in the calculation. Improvement in Retinal Sensitivity in center grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points out of the 16 central points.

Data from ClinicalTrials.gov

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Secondary Outcomes

Part 1: Percentage of Study Eyes With ≥7 dB Improvement From Baseline at ≥5 Points Out of the 16 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry

MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '\< 0', '0' or a positive integer. The point labelled as '\< 0' was assigned a value of '-1' by MAIA in the calculation. Improvement in Retinal Sensitivity in center grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points out of the 16 central points.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Study Eyes With ≥7 dB Improvement From Baseline at ≥5 Points Out of the 68 Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry

MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '\< 0', '0' or a positive integer. The point labelled as '\< 0' was assigned a value of '-1' by MAIA in the calculation. Improvement in Retinal Sensitivity in whole grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points of the grid as a whole (68 points).

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Change From Baseline in Mean Sensitivity of the 16 Central Loci Points Assessed by MAIA Microperimetry

MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '\< 0', '0' or a positive integer. The point labelled as '\< 0' is assigned a value of '-1' by MAIA in the calculation. Improvement in mean sensitivity in center grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points out of the 16 central points. Here negative values indicate a decline in retinal sensitivity.

Time frame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Change From Baseline in Mean Sensitivity of the 68 Central Loci Points Assessed by MAIA Microperimetry

MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '\< 0', '0' or a positive integer. The point labelled as '\< 0' is assigned a value of '-1' by MAIA in the calculation. Improvement in mean sensitivity in whole grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points of the grid as a whole (68 points). Here negative values indicate a decline in retinal sensitivity.

Time frame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Change From Baseline in Mean Best Corrected Visual Acuity (BCVA) Reported as Letters

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was reported as number of letters read correctly by the participants using the ETDRS Scale (ranging from 0 to 100 letters). 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.

Time frame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Change From Baseline in Mean Low Luminance Visual Acuity (LLVA) Reported as Letters

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters). 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 LLVA.

Time frame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Eyes With a ≥15 Letters Increase From Baseline for BCVA

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥15 letters increase from baseline for BCVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Eyes With a ≥15 Letters Increase From Baseline for LLVA

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥15 letters increase from baseline for LLVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Eyes With a ≥10 Letters Increase From Baseline for BCVA

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥10 letters increase from baseline for BCVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Eyes With a ≥10 Letters Increase From Baseline for LLVA

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥10 letters increase from baseline for LLVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Eyes With a ≥5 Letters Increase From Baseline for BCVA

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters increase from baseline for BCVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Eyes With a ≥5 Letters Increase From Baseline for LLVA

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters increase from baseline for LLVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Eyes With a ≥15 Letters Loss From Baseline for BCVA

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥15 letters loss from baseline for BCVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Eyes With a ≥15 Letters Loss From Baseline for LLVA

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥15 letters loss from baseline for LLVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Eyes With a ≥10 Letters Loss From Baseline for BCVA

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥10 letters loss from baseline for BCVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Eyes With a ≥10 Letters Loss From Baseline for LLVA

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥10 letters loss from baseline for LLVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Eyes With a ≥5 Letters Loss From Baseline for BCVA

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters loss from baseline for BCVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Eyes With a ≥5 Letters Loss From Baseline for LLVA

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters loss from baseline for LLVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Eyes With Change From Baseline > -5 Letters for BCVA

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. 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. Percentage of eyes with a change from baseline of ≥ -5 letters for BCVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Percentage of Eyes With Change From Baseline > -5 Letters for LLVA

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. 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. Percentage of eyes with a change from baseline of ≥ -5 letters for LLVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Change From Baseline in Central Ellipsoid Area

Spectral Domain Optical Coherence Tomography (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 a decline in central ellipsoid area.

Time frame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Change From Baseline in Central Horizontal Ellipsoid Width

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 a decline in central horizontal ellipsoid width.

Time frame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Change From Baseline in Fundus Autofluoroscence- Mean Total Area of Preserved Autofluoroscence

Fundus Autofluoroscence was used to assess the total area of preserved autofluoroscence. Areas of preserved AF were identified as well-demarcated regions of relative hyper autofluorescence (hyper AF) compared with the background areas of surrounding atrophy. A negative change from baseline indicates a decline in total area of preserved autofluoroscence.

Time frame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Change From Baseline in Fundus Autofluoroscence- Mean Distance From Foveal Center (FC) to Nearest Border of Preserved Autofluoroscence

Fundus Autofluoroscence was used to assess the distance from FC to nearest border of preserved autofluoroscence. A negative change from baseline indicates a decline in the total area of preserved autofluoroscence.

Time frame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24

Part 1: Change From Baseline in Mean Volume of 30-Degree Hill of Vision

Visual field testing was performed to assess the volume of 30-degree hill vision, reported as dBs. Reliability Factor (RF)=number of false positive responses + number of false negative responses/number of false positive presentations + number of false negative presentations\*100. If there are 0 responses, then RF value=0. RFpositive=number of false positive responses/number of false positive presentations\*100. If RF≤ 20% measurement is considered reliable. If 20% \< RF ≤ 25% and RFpositive ≤ 10% measurement is also considered reliable. Otherwise if 20% \< RF ≤ 25% and RFpositive \> 10%, or RF \> 25%, measurement is not reliable. Only reliable measurements were included for analysis of this outcome measure. Here negative values indicate decline in volume of 30-degree hill vision.

Time frame: Baseline, Months 6, 12, and 24

Part 1: Change From Baseline in Mean Volume of Full Field Hill of Vision

Visual field testing was performed to assess the volume of full field of hill vision, reported as dBs. RF =number of false positive responses + number of false negative responses/number of false positive presentations + number of false negative presentations\*100. If there are 0 responses, then RF value=0. RFpositive=number of false positive responses/number of false positive presentations\*100. If RF≤ 20% measurement is considered reliable. If 20% \< RF ≤ 25% and RFpositive ≤ 10% measurement is also considered reliable. Otherwise if 20% \< RF ≤ 25% and RFpositive \> 10%, or RF \> 25%, measurement is not reliable. Only reliable measurements were included for analysis of this outcome measure. Here negative values indicate decline in volume of 30-degree hill vision.

Time frame: Baseline, Months 6, 12, and 24

Part 1: Change From Baseline in Contrast Sensitivity (CS) Score

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

Time frame: Baseline, Months 3, 6, 12, and 24

Part 2: Percentage of Study Eyes With ≥7 dB Improvement From Baseline at ≥5 Points Out of the 16 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry

MAIA microperimetry assessment was measured in dBs using a 10-2 grid of 68 points. Each point was labelled as '\< 0', '0' or a positive integer. The point labelled as '\< 0' is assigned a value of '-1' by MAIA in the calculation. Improvement in mean sensitivity in center grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points out of the 16 central points.

Time frame: Months 1, 2, 3, 6, and 9

Part 2: Percentage of Study Eyes With ≥7 dB Improvement From Baseline at ≥5 Points Out of the 68 Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry

MAIA microperimetry assessment was measured in dBs using a 10-2 grid of 68 points. Each point was labelled as '\< 0', '0' or a positive integer. The point labelled as '\< 0' was assigned a value of '-1' by MAIA in the calculation. Improvement in mean sensitivity in whole grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points of the grid as a whole (68 points).

Time frame: Months 1, 2, 3, 6, 9, and 12

Part 2: Change From Baseline in Mean Sensitivity of the 16 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry

MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '\< 0', '0' or a positive integer. The point labelled as '\< 0' was assigned a value of '-1' by MAIA in the calculation. Mean Sensitivity in center grid was defined as the mean in dB of the 16 points located in the center of the grid. Here negative values indicate a decline in retinal sensitivity.

Time frame: Baseline, Months 1, 2, 3, 6, 9, and 12

Part 2: Change From Baseline in Mean Sensitivity of the 68 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry

MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '\< 0', '0' or a positive integer. The point labelled as '\< 0' was assigned a value of '-1' by MAIA in the calculation. Improvement in mean ensitivity in whole grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points of the grid as a whole (68 points). Here negative values indicate a decline in retinal sensitivity.

Time frame: Baseline, Months 1, 2, 3, 6, 9, and 12

Part 2: Change From Baseline in BCVA Reported as Letters

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was reported as number of letters read correctly by the participant, using the ETDRS Scale (ranging from 0 to 100 letters). 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 a decline in BCVA.

Time frame: Baseline, Months 1, 2, 3, 6, 9, and 12

Part 2: Change From Baseline in Mean LLVA Reported as Letters

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the participant, using the ETDRS Scale (ranging from 0 to 100 letters). 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 a decline in LLVA.

Time frame: Baseline, Months 1, 3, 6, 9, and 12

Part 2: Percentage of Eyes With a ≥15 Letter Increase From Baseline for BCVA

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥15 letters increase from baseline for BCVA were reported for study and non-study eyes.

Time frame: Months 1, 2, 3, 6, 9, and 12

Part 2: Percentage of Eyes With a ≥15 Letter Increase From Baseline for LLVA

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥15 letters increase from baseline for LLVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, and 12

Part 2: Percentage of Eyes With a ≥10 Letter Increase From Baseline for BCVA

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. 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. Percentage of eyes with a ≥10 letters increase from baseline for BCVA were reported for study and non-study eyes.

Time frame: Months 1, 2, 3, 6, 9, and 12

Part 2: Percentage of Eyes With a ≥10 Letter Increase From Baseline for LLVA

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥10 letters increase from baseline for LLVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, and 12

Part 2: Percentage of Eyes With a ≥5 Letter Increase From Baseline for BCVA

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters increase from baseline for BCVA were reported for study and non-study eyes.

Time frame: Months 1, 2, 3, 6, 9, and 12

Part 2: Percentage of Eyes With a ≥5 Letter Increase From Baseline for LLVA

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters increase from baseline for LLVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, and 12

Part 2: Percentage of Eyes With a ≥15 Letters Loss From Baseline for BCVA

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters loss from baseline for BCVA were reported for study and non-study eyes.

Time frame: Months 1, 2, 3, 6, 9, and 12

Part 2: Percentage of Eyes With a ≥15 Letters Loss From Baseline for LLVA

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥15 letters loss from baseline for LLVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, and 12

Part 2: Percentage of Eyes With a ≥10 Letters Loss From Baseline for BCVA

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥10 letters loss from baseline for BCVA were reported for study and non-study eyes.

Time frame: Months 1, 2, 3, 6, 9, and 12

Part 2: Percentage of Eyes With a ≥10 Letters Loss From Baseline for LLVA

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥10 letters loss from baseline for LLVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, and 12

Part 2: Percentage of Eyes With a ≥5 Letters Loss From Baseline for BCVA

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters loss from baseline for BCVA were reported for study and non-study eyes.

Time frame: Months 1, 2, 3, 6, 9, and 12

Part 2: Percentage of Eyes With a ≥5 Letters Loss From Baseline for LLVA

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters loss from baseline for LLVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, and 12

Part 2: Percentage of Eyes With Change From Baseline >-5 Letters for BCVA

BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a change from baseline of ≥ -5 letters for BCVA were reported for study and non-study eyes.

Time frame: Months 1, 2, 3, 6, 9, and 12

Part 2: Percentage of Eyes With Change From Baseline >-5 Letters for LLVA

LLVA was measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters were read at a distance of 4 meters from the chart. If \<20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a change from baseline of ≥ -5 letters for LLVA were reported for study and non-study eyes.

Time frame: Months 1, 3, 6, 9, and 12

Part 2: Change From Baseline in Volume of 30-Degree Hill of Vision Assessed by Octopus 900

Visual field testing was performed to assess the volume of 30-degree hill vision, reported as dBs. RF=number of false positive responses + number of false negative responses/number of false positive presentations + number of false negative presentations\*100. If there are 0 responses, then RF value=0. RFpositive=number of false positive responses/number of false positive presentations\*100. If RF≤ 20% measurement is considered reliable. If 20% \< RF ≤ 25% and RFpositive ≤ 10% measurement is also considered reliable. Otherwise if 20% \< RF ≤ 25% and RFpositive \> 10%, or RF \> 25%, measurement is not reliable. Only reliable measurements were included for analysis of this outcome measure. Here negative values indicate decline in the volume of 30-degree hill vision.

Time frame: Baseline, Months 3, 6, and 12

Part 2: Change From Baseline in Volume of Full Field Hill of Vision Assessed by Octopus 900

Visual field testing was performed to assess the volume of full field of hill vision, reported as dBs. RF=number of false positive responses + number of false negative responses/number of false positive presentations + number of false negative presentations\*100. If there are 0 responses, then RF value=0. RFpositive=number of false positive responses/number of false positive presentations\*100. If RF≤ 20% measurement is considered reliable. If 20% \< RF ≤ 25% and RFpositive ≤ 10% measurement is also considered reliable. Otherwise if 20% \< RF ≤ 25% and RFpositive \> 10%, or RF \> 25%, measurement is not reliable. Only reliable measurements were included for analysis of this outcome measure. Here negative values indicate decline in volume of full field hill vision.

Time frame: Baseline, Months 3, 6, and 12