A Study of Danicopan in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration

FAF provides high-contrast retinal images particularly valuable for the detection of atrophic areas. FAF images of the study eye were taken and sent to the reading center for total GA lesion area measurement. The total GA lesion area (mm^2) was transformed into sqrt (mm). Greater area affected means a worse outcome than smaller area affected.

FAF provides high-contrast retinal images particularly valuable for the detection of atrophic areas. FAF images of the study eye were taken and sent to the reading center for total GA lesion area (mm^2) measurement. Greater area affected means a worse outcome than smaller area affected.

Photoreceptor loss was assessed by measuring the percent of macular EZ total attenuation using SD-OCT. The EZ was considered to be formed mainly by mitochondria within the ellipsoid layer of the outer portion of the inner segments of the photoreceptors. In SD-OCT, decreases in the integrity and intensity of the EZ have been correlated with the reduction in cone photoreceptors and retinal sensitivity in retinal degenerative diseases. Lower increase in percentage means a better outcome. Higher increase in percentage means a worse outcome.

Photoreceptor degradation was assessed by measuring the percent of macular EZ partial attenuation using SD-OCT. The EZ was considered to be formed mainly by mitochondria within the ellipsoid layer of the outer portion of the inner segments of the photoreceptors. In SD-OCT, decreases in the integrity and intensity of the EZ have been correlated with the reduction in cone photoreceptors and retinal sensitivity in retinal degenerative diseases. Lower increase in percentage means a better outcome. Higher increase in percentage means a worse outcome.

The ONL - RPE mean central 1 mm subfield thickness refers to the average thickness of the retinal layers between the ONL and RPE measured within a 1 mm radius from the foveal center (the central point of the retina).

The ONL - RPE mean central macular 2 mm subfield thickness refers to the thickness of the retina in the central part of the macula, specifically within a 2 mm radius.

The EZ - RPE macular volume refers to the volume of the retinal tissue between the EZ and the RPE, specifically within the macular region. Changes in EZ-RPE volume indicate the presence or progression of diseases affecting the outer retina.

The EZ - RPE mean central 1 mm subfield thickness is a measurement of the thickness of the ellipsoid zone, a layer within the retina, in the central 1 mm region. Changes in EZ-RPE thickness indicate damage or dysfunction within the photoreceptors, which is associated with various eye diseases like AMD.

The EZ - RPE mean central macular 2 mm thickness measurement reflects the distance between the outer border of the EZ and the inner border of the RPE layer, typically within a central 2 mm area. Decreased EZ-RPE thickness is an early indicator of disease, such as in dry AMD, where a thinning or loss of the EZ is a hallmark. Changes in EZ-RPE thickness is used to monitor treatment response in conditions like AMD.

The percentage of total attenuation of the EZ in the central 1 mm subfield is reported.

The percentage of partial attenuation of the EZ in the central 1 mm subfield is reported.

The percentage of total attenuation of the EZ in the central macular 2 mm subfield is reported.

The percentage of partial attenuation of the EZ in the central macular 2 mm subfield is reported.

Sub-RPE compartment measures reflect the disease burden between the RPE and Bruch's membrane. The sub-RPE central 1 mm mean thickness refers to the average thickness of the retina within a 1-mm diameter circular area centered around the fovea (the central part of the retina).

Sub-RPE compartment measures reflect the disease burden between the RPE and Bruch's membrane. The sub-RPE central macular 2 mm subfield thickness refers to the thickness of the retina within a 2-mm radius in the central part of the macula.

Sub-RPE compartment measures reflect the disease burden between the RPE and Bruch's membrane. The panmacular sub-RPE volume refers to the total volume of fluid or space located underneath the RPE across the entire macula (the central part of the retina).

Macular total RPE attenuation refers to the degree of thinning or loss of the RPE in the macula, the central part of the retina responsible for sharp, detailed vision. This was measured as a percentage of the macular area affected.

The percentage of total attenuation of the RPE in the central 1 mm subfield is reported.

The percentage of total attenuation of the RPE in the central macular 2 mm subfield is reported.

ETDRS charts present a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows; there is a total of 14 lines (70 letters), with letter size increasing further geometrically and equivalently in every line by a factor of 1.2589 (or 0.1 log unit), moving up the chart. Minimum score of zero, maximum score of 100. Change from baseline: a more negative score is worse outcome, a more positive score is better outcome. A lower score means less letters were read correctly (worse outcome) and a higher score means more letters were read correctly (better outcome).

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. 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. Change from baseline: a negative score indicates decline in LLVA.

LLD score was calculated as the difference between BCVA and LLVA (BCVA-LLVA) scores. BCVA and LLVA were reported as the 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. LLD is a measure of visual acuity impairment in low-light conditions. A higher LLD score indicates a greater difference between vision in bright and dim light, suggesting a more significant loss of visual function in low-luminance settings.

MNRead acuity cards were continuous-text reading-acuity cards suitable for measuring the reading acuity and reading speed of normal and low-vision participants. The MNRead acuity cards consisted of single, simple sentences with equal numbers of characters. A stopwatch was used to record time to a tenth of a second. Sentences that could not be read or were not attempted due to vision should be recorded as 0 for time and 10 for errors. The Radner Reading Cards were suitable for measuring reading speed, reading visual acuity, and critical print size. The reading test was stopped when the reading time was longer than 20 seconds or when the participant was making severe errors. A negative change from baseline indicates a decrease in the monocular reading speed; disease worsening.

The NEI VFQ-25 instrument measures dimensions of self-reported vision-targeted health status of individuals with chronic eye conditions. The NEI VFQ-25 consists of 11 vision related domains: global vision rating, difficulty with near vision activities, difficulty with distance vision activities, limitations in social function related to vision, role limitations, dependency on others due to vision, mental health symptoms due to vision, driving difficulties, limitations with peripheral- and color-vision, and ocular pain. The NEI VFQ-25 also includes a single item measuring general health. A composite score averages the vision related domains and ranges from 0 (worse) to 100 (best). A higher score represents better functioning. A negative change from baseline indicates a decrease in the visual functioning; disease worsening.

All values below the limit of quantification (<0.1 nanograms [ng]/milliliter [mL]) were set to 0 for calculation of summary statistics.

Serum AP functional activity was measured by the Wieslab functional immunoassay method.

An adverse event (AE) was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), or an important medical event or reaction. A TEAE was defined as any AE that started during or after the first dose of study intervention. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.