Choroideremia
Conditions
Keywords
NightstaRx, NSR-REP1, Gene Therapy, AAV, REP1, Timrepigene Emparvovec
Brief summary
The objective of the study is to evaluate the efficacy and safety of a single sub-retinal injection of BIIB111 in participants with choroideremia (CHM).
Detailed description
This study was previously posted by NightstaRx Ltd. In October 2020, sponsorship of the trial was transferred to Biogen.
Interventions
GENETICBIIB111
Administered as specified in the treatment arm.
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Are willing and able to give informed consent for participation in the study. * Have a documented genetically-confirmed diagnosis of CHM. * Have active disease clinically visible within the macular region in the study eye. * Have a BCVA of 34-73 ETDRS letters (equivalent to worse than or equal to 6/12 or 20/40 Snellen acuity, but better than or equal to 6/60 or 20/200 Snellen acuity) in the study eye. Key
Exclusion criteria
* Have a history of amblyopia in the eligible eye. * Have had previous intraocular surgery performed in the study eye within 3 months of Visit 1. * Have any other significant ocular or non-ocular disease/disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the results of the study, or the participant's ability to participate in the study. * Have participated in another research study involving an investigational product in the past 12 weeks or received a gene/cell-based therapy at any time previously. * Are unwilling to use barrier contraception methods, or abstain from sexual intercourse, for a period of 3 months, if treated with AAV2-REP1. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Month 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in BCVA at Month 12 Reported as Letters Measured by the ETDRS Chart in Study Eye | 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. |
| Percentage of Participants With a ≥10 -Letter Improvement From Baseline in BCVA at Month 12 Measured by the ETDRS Chart | 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. |
| 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 | 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. |
| Change From Baseline in BCVA at Months 4 and 8 Reported as Letters Measured by the ETDRS Chart | Baseline, Months 4 and 8 | 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. |
| Change From Baseline in Total Area of Preserved Autofluorescence (AF) at Month 12 in Study Eye | 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. |
| Change From Baseline in Distance From Foveal Center to Nearest Border of Preserved AF at Month 12 in Study Eye | 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. |
| Change From Baseline in the Foveal Subfield Thickness Using Spectral Domain Optical Coherence Tomography (SD-OCT) at Month 12 in Study Eye | 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. |
| Change From Baseline in the Total Macular Volume Using SD-OCT at Month 12 in Study Eye | 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. |
| Change From Baseline in the Central Horizontal Ellipsoid Width Using SD-OCT at Month 12 in Study Eye | 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. |
| Change From Baseline in the Central Ellipsoid Area Using SD-OCT at Month 12 in Study Eye | 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. |
| Change From Baseline in the Choroidal Thickness Using SD-OCT at Month 12 in Study Eye | 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. |
| Change From Baseline in the Mean Retinal Sensitivity Using Microperimetry at Month 12 in Study Eye | 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. |
| Change From Baseline in the Bivariate Contour Ellipse Area 63% Using Microperimetry at Month 12 in Study Eye | 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%. |
| Change From Baseline in the Bivariate Contour Ellipse Area 95% Using Microperimetry at Month 12 in Study Eye | 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%. |
| Change From Baseline in Contrast Sensitivity Score at Month 12 in Study Eye | Baseline, Month 12 | 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. |
| Change From Baseline in Colour Vision Total Error Score at Month 12 in Study Eye | 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. |
| Change From Baseline in Reading Speed Test at Month 12 in Study Eye | 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. |
| Change From Baseline in the 25-Item Visual Function Questionnaire (VFQ-25) Composite Scores at Month 12 in Study Eye | 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. |
Countries
Canada, Denmark, Finland, France, Germany, Netherlands, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Untreated Control Group Participants received no sham surgery or study medication to allow for a controlled comparison. | 65 |
| BIIB111 Low Dose 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). | 34 |
| 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). | 65 |
| Total | 164 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Reason Not Specified | 2 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | Untreated Control Group | BIIB111 Low Dose | BIIB111 High Dose | Total |
|---|---|---|---|---|
| Age, Continuous | 49.4 years STANDARD_DEVIATION 13.73 | 49.8 years STANDARD_DEVIATION 12.62 | 47.5 years STANDARD_DEVIATION 12.91 | 48.7 years STANDARD_DEVIATION 13.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 26 Participants | 54 Participants | 131 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 7 Participants | 7 Participants | 25 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Not Reported | 7 Participants | 4 Participants | 5 Participants | 16 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 55 Participants | 30 Participants | 59 Participants | 144 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 65 Participants | 34 Participants | 65 Participants | 164 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 65 | 0 / 34 | 0 / 65 |
| other Total, other adverse events | 9 / 65 | 30 / 34 | 54 / 65 |
| serious Total, serious adverse events | 10 / 65 | 9 / 34 | 11 / 65 |
Outcome results
Primary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Untreated Control Group | 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 |
| Untreated Control Group | 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 |
| BIIB111 Low Dose | 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 | 2.9 percentage of participants |
| BIIB111 Low Dose | 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 |
| BIIB111 High Dose | 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 | 4.6 percentage of participants |
| BIIB111 High Dose | 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 | 3.1 percentage of participants |
p-value: =0.35495% CI: [-3.1, 15]Fisher's Exact
p-value: =0.24595% CI: [-1.4, 12.8]Fisher's Exact
Secondary
Change From Baseline in BCVA at Month 12 Reported as Letters Measured by the ETDRS Chart in Study Eye
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.
Time frame: Baseline, Month 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Untreated Control Group | Change From Baseline in BCVA at Month 12 Reported as Letters Measured by the ETDRS Chart in Study Eye | -2.3 letters |
| BIIB111 Low Dose | Change From Baseline in BCVA at Month 12 Reported as Letters Measured by the ETDRS Chart in Study Eye | -1.5 letters |
| BIIB111 High Dose | Change From Baseline in BCVA at Month 12 Reported as Letters Measured by the ETDRS Chart in Study Eye | -0.3 letters |
Secondary
Change From Baseline in BCVA at Months 4 and 8 Reported as Letters Measured by the ETDRS Chart
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Untreated Control Group | 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 |
| Untreated Control Group | 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 |
| Untreated Control Group | 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 |
| Untreated Control Group | 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 |
| BIIB111 Low Dose | 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 | 1.9 letters | Standard Deviation 7.06 |
| BIIB111 Low Dose | 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 | -0.4 letters | Standard Deviation 14.16 |
| BIIB111 Low Dose | 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 | 0.9 letters | Standard Deviation 6.67 |
| BIIB111 Low Dose | 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 | -1.1 letters | Standard Deviation 13.13 |
| BIIB111 High Dose | 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 | 0.6 letters | Standard Deviation 11.11 |
| BIIB111 High Dose | 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 | 0.1 letters | Standard Deviation 11.71 |
| BIIB111 High Dose | 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 | 2.0 letters | Standard Deviation 6.63 |
| BIIB111 High Dose | 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 | 1.6 letters | Standard Deviation 5.91 |
Secondary
Change From Baseline in Colour Vision Total Error Score at Month 12 in Study Eye
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.
Time frame: Baseline, Month 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Untreated Control Group | 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 |
| BIIB111 Low Dose | Change From Baseline in Colour Vision Total Error Score at Month 12 in Study Eye | 43.5915 score on a scale | Standard Error 31.772 |
| BIIB111 High Dose | Change From Baseline in Colour Vision Total Error Score at Month 12 in Study Eye | 54.3777 score on a scale | Standard Error 24.0358 |
Secondary
Change From Baseline in Contrast Sensitivity Score at Month 12 in Study Eye
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Untreated Control Group | Change From Baseline in Contrast Sensitivity Score at Month 12 in Study Eye | -0.0595 score on a scale | Standard Error 0.0315 |
| BIIB111 Low Dose | Change From Baseline in Contrast Sensitivity Score at Month 12 in Study Eye | -0.0130 score on a scale | Standard Error 0.0417 |
| BIIB111 High Dose | Change From Baseline in Contrast Sensitivity Score at Month 12 in Study Eye | -0.0386 score on a scale | Standard Error 0.0304 |
Secondary
Change From Baseline in Distance From Foveal Center to Nearest Border of Preserved AF at Month 12 in Study Eye
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.
Time frame: Baseline, Month 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Untreated Control Group | 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 |
| BIIB111 Low Dose | Change From Baseline in Distance From Foveal Center to Nearest Border of Preserved AF at Month 12 in Study Eye | 23.6171 micrometers (µm) | Standard Error 12.3765 |
| BIIB111 High Dose | Change From Baseline in Distance From Foveal Center to Nearest Border of Preserved AF at Month 12 in Study Eye | 21.1660 micrometers (µm) | Standard Error 9.1863 |
Secondary
Change From Baseline in Reading Speed Test at Month 12 in Study Eye
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.
Time frame: Baseline, Month 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Untreated Control Group | Change From Baseline in Reading Speed Test at Month 12 in Study Eye | -149.5590 words per minute | Standard Error 10.9857 |
| BIIB111 Low Dose | Change From Baseline in Reading Speed Test at Month 12 in Study Eye | -122.1333 words per minute | Standard Error 14.3276 |
| BIIB111 High Dose | Change From Baseline in Reading Speed Test at Month 12 in Study Eye | -127.4706 words per minute | Standard Error 9.911 |
Secondary
Change From Baseline in the 25-Item Visual Function Questionnaire (VFQ-25) Composite Scores at Month 12 in Study Eye
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.
Time frame: Baseline, Month 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Untreated Control Group | 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 |
| BIIB111 Low Dose | Change From Baseline in the 25-Item Visual Function Questionnaire (VFQ-25) Composite Scores at Month 12 in Study Eye | 1.7236 score on a scale | Standard Error 1.6624 |
| BIIB111 High Dose | Change From Baseline in the 25-Item Visual Function Questionnaire (VFQ-25) Composite Scores at Month 12 in Study Eye | 0.7964 score on a scale | Standard Error 1.2308 |
Secondary
Change From Baseline in the Bivariate Contour Ellipse Area 63% Using Microperimetry at Month 12 in Study Eye
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%.
Time frame: Baseline, Month 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Untreated Control Group | 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 |
| BIIB111 Low Dose | Change From Baseline in the Bivariate Contour Ellipse Area 63% Using Microperimetry at Month 12 in Study Eye | -3.3771 square degrees (deg^2) | Standard Error 1.6405 |
| BIIB111 High Dose | Change From Baseline in the Bivariate Contour Ellipse Area 63% Using Microperimetry at Month 12 in Study Eye | -2.5555 square degrees (deg^2) | Standard Error 1.2403 |
Secondary
Change From Baseline in the Bivariate Contour Ellipse Area 95% Using Microperimetry at Month 12 in Study Eye
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%.
Time frame: Baseline, Month 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Untreated Control Group | 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 |
| BIIB111 Low Dose | Change From Baseline in the Bivariate Contour Ellipse Area 95% Using Microperimetry at Month 12 in Study Eye | -14.6926 deg^2 | Standard Error 5.3134 |
| BIIB111 High Dose | Change From Baseline in the Bivariate Contour Ellipse Area 95% Using Microperimetry at Month 12 in Study Eye | -11.6863 deg^2 | Standard Error 4.0207 |
Secondary
Change From Baseline in the Central Ellipsoid Area Using SD-OCT at Month 12 in Study Eye
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.
Time frame: Baseline, Month 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Untreated Control Group | 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 |
| BIIB111 Low Dose | Change From Baseline in the Central Ellipsoid Area Using SD-OCT at Month 12 in Study Eye | -0.4229 mm^2 | Standard Error 0.0527 |
| BIIB111 High Dose | Change From Baseline in the Central Ellipsoid Area Using SD-OCT at Month 12 in Study Eye | -0.3440 mm^2 | Standard Error 0.0332 |
Secondary
Change From Baseline in the Central Horizontal Ellipsoid Width Using SD-OCT at Month 12 in Study Eye
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.
Time frame: Baseline, Month 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Untreated Control Group | 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 |
| BIIB111 Low Dose | Change From Baseline in the Central Horizontal Ellipsoid Width Using SD-OCT at Month 12 in Study Eye | -116.3811 µm | Standard Error 27.8213 |
| BIIB111 High Dose | Change From Baseline in the Central Horizontal Ellipsoid Width Using SD-OCT at Month 12 in Study Eye | -170.7214 µm | Standard Error 20.4062 |
Secondary
Change From Baseline in the Choroidal Thickness Using SD-OCT at Month 12 in Study Eye
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.
Time frame: Baseline, Month 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Untreated Control Group | Change From Baseline in the Choroidal Thickness Using SD-OCT at Month 12 in Study Eye | -5.4897 µm | Standard Error 2.1873 |
| BIIB111 Low Dose | Change From Baseline in the Choroidal Thickness Using SD-OCT at Month 12 in Study Eye | -7.9579 µm | Standard Error 2.9207 |
| BIIB111 High Dose | Change From Baseline in the Choroidal Thickness Using SD-OCT at Month 12 in Study Eye | -4.6371 µm | Standard Error 2.1446 |
Secondary
Change From Baseline in the Foveal Subfield Thickness Using Spectral Domain Optical Coherence Tomography (SD-OCT) at Month 12 in Study Eye
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.
Time frame: Baseline, Month 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Untreated Control Group | 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 |
| BIIB111 Low Dose | Change From Baseline in the Foveal Subfield Thickness Using Spectral Domain Optical Coherence Tomography (SD-OCT) at Month 12 in Study Eye | -19.8654 µm | Standard Error 3.6998 |
| BIIB111 High Dose | Change From Baseline in the Foveal Subfield Thickness Using Spectral Domain Optical Coherence Tomography (SD-OCT) at Month 12 in Study Eye | -15.7993 µm | Standard Error 2.7233 |
Secondary
Change From Baseline in the Mean Retinal Sensitivity Using Microperimetry at Month 12 in Study Eye
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.
Time frame: Baseline, Month 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Untreated Control Group | Change From Baseline in the Mean Retinal Sensitivity Using Microperimetry at Month 12 in Study Eye | -0.3443 dBs | Standard Error 0.1134 |
| BIIB111 Low Dose | Change From Baseline in the Mean Retinal Sensitivity Using Microperimetry at Month 12 in Study Eye | -0.2965 dBs | Standard Error 0.1478 |
| BIIB111 High Dose | Change From Baseline in the Mean Retinal Sensitivity Using Microperimetry at Month 12 in Study Eye | -0.5015 dBs | Standard Error 0.1112 |
Secondary
Change From Baseline in the Total Macular Volume Using SD-OCT at Month 12 in Study Eye
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.
Time frame: Baseline, Month 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Untreated Control Group | 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 |
| BIIB111 Low Dose | Change From Baseline in the Total Macular Volume Using SD-OCT at Month 12 in Study Eye | -0.2876 cubic millimeters (mm^3) | Standard Error 0.0646 |
| BIIB111 High Dose | Change From Baseline in the Total Macular Volume Using SD-OCT at Month 12 in Study Eye | -0.2088 cubic millimeters (mm^3) | Standard Error 0.0476 |
Secondary
Change From Baseline in Total Area of Preserved Autofluorescence (AF) at Month 12 in Study Eye
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.
Time frame: Baseline, Month 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Untreated Control Group | 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 |
| BIIB111 Low Dose | Change From Baseline in Total Area of Preserved Autofluorescence (AF) at Month 12 in Study Eye | -0.5413 square millimeters (mm^2) | Standard Error 0.0501 |
| BIIB111 High Dose | Change From Baseline in Total Area of Preserved Autofluorescence (AF) at Month 12 in Study Eye | -0.5136 square millimeters (mm^2) | Standard Error 0.0371 |
Secondary
Percentage of Participants With a ≥10 -Letter Improvement From Baseline in BCVA at Month 12 Measured by the ETDRS Chart
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.
Time frame: Month 12
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Untreated Control Group | 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 |
| Untreated Control Group | 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 |
| BIIB111 Low Dose | Percentage of Participants With a ≥10 -Letter Improvement From Baseline in BCVA at Month 12 Measured by the ETDRS Chart | Study Eye | 17.6 percentage of participants |
| BIIB111 Low Dose | Percentage of Participants With a ≥10 -Letter Improvement From Baseline in BCVA at Month 12 Measured by the ETDRS Chart | Fellow Eye | 8.8 percentage of participants |
| BIIB111 High Dose | Percentage of Participants With a ≥10 -Letter Improvement From Baseline in BCVA at Month 12 Measured by the ETDRS Chart | Study Eye | 13.8 percentage of participants |
| BIIB111 High Dose | Percentage of Participants With a ≥10 -Letter Improvement From Baseline in BCVA at Month 12 Measured by the ETDRS Chart | Fellow Eye | 6.2 percentage of participants |
95% CI: [5.3, 32.2]
95% CI: [3.5, 23]
Secondary
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
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.
Time frame: Month 12
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Untreated Control Group | 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 |
| Untreated Control Group | 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 |
| BIIB111 Low Dose | 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 | 70.6 percentage of participants |
| BIIB111 Low Dose | 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 | 85.3 percentage of participants |
| BIIB111 High Dose | 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 | 83.1 percentage of participants |
| BIIB111 High Dose | 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 | 90.8 percentage of participants |
95% CI: [-17.2, 21]
95% CI: [0.3, 30.1]