An Extension Study to Evaluate the Long-term Safety and Efficacy of Pegcetacoplan (APL-2) in Subjects With Geographic Atrophy Secondary to AMD

The change in GA lesion area was measured by a qualified central reading center based on fundus autofluorescence (FAF) images.

The mean rate of change in GA area was analyzed by use of a piecewise linear mixed effect model assuming time as continuous and piecewise linear in FAS based on FAF images.

The NL-BCVA was assessed by early treatment diabetic retinopathy study (ETDRS) chart prior to dilating the eyes at a starting distance of 4 meters and ranged from 0 (least score) to 100 (best score). If the 4-meter score was >19 letters read correctly, the visual acuity score was the sum of total letters correctly read at 4 meters plus the addition of 30. If the 4-meter score was ≤19 letters read correctly, the visual acuity score was the sum of total letters read correctly at 4 meters and total letters read correctly at the 1-meter distance. If no letters were read correctly at either the 4-meter distance or the 1-meter distance, the visual acuity score was 0. A negative change from baseline indicates loss in visual acuity.

The LL-BCVA was assessed by early treatment diabetic retinopathy study (ETDRS) chart prior to dilating the eyes at a starting distance of 4 meters and ranged from 0 (least score) to 100 (best score). It was measured by placing a neutral density trial lens causing a reduction of 2.0 log units in luminance. If the 4-meter score was >19 letters read correctly, the visual acuity score was the sum of total letters correctly read at 4 meters plus the addition of 30. If the 4-meter score was ≤19 letters read correctly, the visual acuity score was the sum of total letters read correctly at 4 meters and total letters read correctly at the 1-meter distance. If no letters were read correctly at either the 4-meter distance or the 1-meter distance, the visual acuity score was 0. A negative change from baseline indicates loss in visual acuity.

The maximum reading speed of the study eye was calculated per Minnesota Low-Vision Reading Test (MNRead) or Radner user manuals, with adjustment for reading inaccuracy. An additional step to cap resulting reading speed values at a maximum of 300 words per minute was implemented. Maximum reading speed was calculated as the mean of the three highest nonzero reading speeds (or two, or one value, as available), except when all words per minute were calculated as 0: then the maximum reading speed was calculated as 0. A negative change from baseline indicated a decrease in the monocular reading speed; disease worsening.

The maximum reading speed was calculated per MNRead or Radner user manuals, with adjustment for reading inaccuracy. An additional step to cap resulting reading speed values at a maximum of 300 words per minute was implemented. Maximum reading speed was calculated as the mean of the three highest nonzero reading speeds (or two, or one value, as available), except when all words per minute were calculated as 0: then the maximum reading speed was calculated as 0. A negative change from baseline indicated a decrease in the binocular reading speed; disease worsening.

The number of absolute scotomatous points was determined from mesopic microperimetry as an assessment of the macular functional response.

Macular sensitivity was assessed by mesopic microperimetry. A negative change from baseline indicates a decrease in the macular sensitivity.

Microperimetry was conducted to assess the bivariate contour ellipse area 95%.

The FRI index is an individualized assessment of functional reading independence. The questionnaire has 7 items with one total index score. Scores derived from the index range from 1 (unable to do independently) to 4 (total independence) with higher scores indicating higher functional reading independence. A negative change from baseline indicated a decrease in the FRI; disease worsening. Least squares mean was calculated using a mixed effect model for repeated measure (MMRM) model.

The NEI-VFQ-25 is an interviewer-administered questionnaire designed to assess participant-reported visual function. It is a 25-item questionnaire with a composite score and covers 12 domains of functional health status and well-being (general health, general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, and peripheral vision). Scoring yields 12 subscales based on the 12 domains covered in the questionnaire. These scales are scored from 0 to 100 with higher scores indicating better visual function. A composite score is the average of the vision-targeted sub-scale scores, excluding the general health rating question. A negative change from baseline indicated a decrease in visual functioning; disease worsening.

The NEI-VFQ-25 is an interviewer-administered questionnaire designed to assess participant-reported visual function. It is a 25-item questionnaire with a composite score and covers 12 domains of functional health status and well-being (general health, general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, and peripheral vision). Scoring yields 12 subscales based on the 12 domains covered in the questionnaire. The possible score range is 0 to 100 with higher scores indicating better visual function. A negative change from baseline indicated a decrease in visual functioning; disease worsening. Near activities are defined as reading ordinary print in newspapers, performing work or hobbies requiring near vision, or finding something on a crowded shelf.

The NEI-VFQ-25 is a 25-item questionnaire with a composite score and covers 12 domains of functional health status and well-being. A distance activity subscale score one of the domains is the average of 3 items: 8 (How much difficulty do you have reading street signs or the names of stores?), 9 (Because of your eyesight, how much difficulty do you have going down steps, stairs, or curbs in dim light or at night?) and 14 (Because of your eyesight, how much difficulty do you have going out to see movies, plays, or sports events?). The possible score range is 0 to 100, with higher scores indicating better visual function. A negative change from baseline indicated a decrease in visual functioning; disease worsening.

The NEI-VFQ-25 is a 25-item questionnaire with a composite score and covers 12 domains of functional health status and well-being. A driving subscale score one of the domains is the average of 3 items: 15c (If currently driving: How much difficulty do you have driving during the day time in familiar places?), 16 (How much difficulty do you have driving at night), and 16a (How much difficulty do you have driving in difficult conditions, such as in bad weather, during rush hour, on the freeway, or in city traffic?). The possible score range is 0 to 100, with higher scores indicating better visual function. A negative change from baseline indicated a decrease in visual functioning; disease worsening.

NEI-VFQ-25 includes 13 additional items under 7 subscales related to general health, general vision, near vision, distance vision, social function, driving, role limitations, well-being or distress and dependency that allow for the calculation of NEI-VFQ-39 scores. The NEI-VFQ composite score is obtained by averaging the vision-related subscales, excluding the general health rating question. The possible score range is 0 to 100, with higher scores indicating better visual function. A negative change from baseline indicated a decrease in visual functioning; disease worsening.

NEI-VFQ-25 includes 13 additional items under 7 subscales, enabling calculation of NEI-VFQ-39 scores. NEI-VFQ near activity subscale score is obtained by averaging 6 items: 5 (How much difficulty do you have reading ordinary print in newspapers), 6 (How much difficulty do you have doing work/hobbies that require you to see up close?), 7 (Because of your eyesight, how much difficulty do you have finding something on a crowded shelf?), A3 (Wearing glasses, how much difficulty do you have reading the small print in a telephone book, on medicine bottle, or on legal forms?), A4 (Because of your eyesight, how much difficulty do you have figuring out bills you receive are accurate?) \& A5 (Because of your eyesight, how much difficulty do you have doing things like shaving, styling your hair or putting on makeup). The possible score range is 0 to 100, with higher scores indicating better visual function. A negative change from baseline indicated reduced visual functioning; disease worsening.

NEI-VFQ-25 includes 13 additional items under 7 subscales, enabling calculation of NEI-VFQ-39 scores. NEI-VFQ near activity subscale score is obtained by averaging 6 items: 8 (How much difficulty do you have reading street signs/names of stores?), 9 (Because of your eyesight, how much difficulty do you have going down steps, stairs/ curbs in dim light/ at night?) and 14 (Because of your eyesight, how much difficulty do you have going out to see movies, plays/sports events?), A6 (Because of your eyesight, how much difficulty do you have recognizing people you know from across a room?), A7 (Because of your eyesight, how much difficulty do you have taking part in active sports/other outdoor activities?) \& A8 (Because of your eyesight, how much difficulty do you have seeing \& enjoying programs on TV?). The possible score range is 0 to 100, with higher scores indicating better visual function. A negative change from baseline indicated reduced visual functioning; disease worsening.