Geographic Atrophy
Conditions
Brief summary
This is a 24-month, Phase III, multicenter, randomized, double-masked, sham-injection controlled study to assess the efficacy and safety of multiple IVT injections of APL-2 in subjects with GA secondary to AMD.
Interventions
DRUGAPL-2
Complement (C3) Inhibitor
OTHERSham Procedure
Subjects will receive a Sham procedure every month
Sponsors
Apellis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The study eye must meet all inclusion criteria. If both eyes meet the inclusion criteria, the eye with the worst visual acuity at the screening visit will be designated as the study eye. If both eyes have the same visual acuity, the right eye will be selected as the study eye. Ocular- specific inclusion criteria apply to the study eye only, unless otherwise specified. * Age ≥ 60 years. * Normal Luminance best corrected visual acuity of 24 letters or better using Early Treatment Diabetic Retinopathy Study (ETDRS) charts (approximately 20/320 Snellen equivalent). * Clinical diagnosis of GA of the macula secondary to AMD as determined by the Investigator and confirmed by the Reading Center. * The GA lesion must meet the following criteria as determined by the central reading center's assessment of Fundus Autofluorescence (FAF) imaging at screening: * Total GA area must be ≥ 2.5 and ≤ 17.5 mm2 (1 and 7 disk areas \[DA\] respectively) * If GA is multifocal, at least one focal lesion must be ≥ 1.25 mm2 (0.5 DA), with the overall aggregate area of GA, as specified above in 4a. * The entire GA lesion must be completely visualized on the macula centered image and must be able to be imaged in its entirety and not contiguous with any areas of peripapillary atrophy. * Presence of any pattern of hyperautofluorescence in the junctional zone of GA. Absence of hyperautofluorescence (i.e. pattern = none) is exclusionary. * Adequate clarity of ocular media, adequate pupillary dilation, and fixation to permit the collection of good quality images as determined by the Investigator. * Meets the following criteria related to microperimetry: * Able to detect fixation target. * Total elapsed time to complete the 10-2 68 point exam is ≤ 30 minutes in duration. * Reliability test ratio must be ≤ 20%. * Subject is willing and able to undertake microperimetry assessment in the opinion of the investigator. * Female subjects must be: * Women of non-child-bearing potential (WONCBP), or * Women of child-bearing potential (WOCBP) with a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study and refrain from breastfeeding for the duration of the study. * Males with female partners of child-bearing potential must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study. * Willing and able to give informed consent and to comply with the study procedures and assessments.
Exclusion criteria
Ocular specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares (LS) Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 12 | Baseline (screening) and Month 12 | The GA lesion area was measured by a quantified central reading center based on FAF images. LS mean was calculated using a mixed effect model for repeated measure (MMRM) model. Baseline was defined as the last available, non-missing observation prior to first study drug administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Baseline (screening) through Month 24 | The mean change in GA lesion area through Month 24 was measured by assuming a piecewise linear trend in time with knots by FAF images at Months 6, 12, 18, and 24 and was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration. |
| LS Mean Change From Baseline in Mean Threshold Sensitivity of All Points of the Study Eye at Month 24 | Baseline (screening) and Month 24 | Mean threshold sensitivity of all points was determined from the mesopic microperimetry as an assessment of the macular functional response. Microperimetry offers the option to test retinal light sensitivity while directly observing the fundus and allows for monitoring of macular function loss associated with GA progression. The microperimetry reading center overlaid the baseline FAF images with GA lesions traced by the imaging reading center and the corresponding macular integrity assessment microperimetry baseline scanning laser ophthalmoscope image and identified perilesional (within 500 microns outside the atrophy border), paralesional (beyond 500 microns outside the atrophy border), and extralesional (outside the atrophy border) loci on the microperimetry grid to determine the mean threshold sensitivity for these 3 areas. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration. |
| LS Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 24 | Baseline (screening) and Month 24 | The GA lesion area was measured by a quantified central reading center based on FAF images. LS mean was calculated using a mixed effect model for repeated measure model. Baseline was defined as the last available, non-missing observation prior to first study drug administration. |
| LS Mean Change From Baseline in Mean Functional Reading Independence (FRI) Index Score at Month 24 | Baseline (screening) and Month 24 | The FRI was an interviewer-administered questionnaire with 7 items on functional reading activities most relevant to GA AMD subjects. It had 1 total index score. For each FRI Index reading activity performed in the past 7 days, subjects were asked about the extent to which they required assistance beyond eyeglasses/contact lenses, including the use of low-vision aids, adjustments in the activity, or help from another subject. Mean FRI Index scores ranged from 1 (unable to do independently) to 4 (totally independent), with higher scores indicating higher functional reading independence. A negative change from baseline indicated a decrease in the FRI; disease worsening. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration. |
| LS Mean Change From Baseline in Normal-Luminance Best-Corrected Visual Acuity (NL-BCVA) Score of the Study Eye at Month 24 | Baseline (screening) and Month 24 | 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 positive change in the value indicated improvement in visual acuity. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration. |
| LS Mean Change From Baseline in Monocular Maximum Reading Speed of the Study Eye at Month 24 | Baseline (screening) and Month 24 | The maximum reading speed of the study eye was calculated per Minnesota Low-Vision Reading Test (MNREAD) or Radner Reading Charts user manuals, with no adjustment for reading inaccuracy. An additional step to cap resulting reading speed values at a maximum of 300 words per minute (wpm) was implemented. Maximum reading speed was calculated as the mean of the 3 highest non-zero reading speeds (or 2, or 1 value, as available), except when all wpm were calculated as 0 then the maximum reading speed was calculated as 0. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration. |
Countries
Australia, Brazil, Canada, Czechia, France, Germany, Israel, Italy, Netherlands, New Zealand, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
This Phase III, randomized, double-masked, sham injection-controlled study was conducted in subjects with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) at 110 sites in 13 countries between 31 Aug 2018 and 28 Jun 2022.
Pre-assignment details
This study consisted of a screening period (up to 30 days), a randomization visit on Day 1, and a treatment period (up to 24 months). Subjects were randomized in a 2:2:1:1 ratio on Day 1 to receive treatment with pegcetacoplan monthly, pegcetacoplan every other month (EOM), sham injection monthly or sham injection EOM, respectively. A total of 637 subjects were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Pegcetacoplan Monthly Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL once monthly for 24 months. | 213 |
| Pegcetacoplan EOM Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL EOM for 24 months. | 212 |
| Sham Pooled Sham Monthly: Subjects received sham injections once monthly for 24 months.
Sham EOM: Subjects received sham injections EOM for 24 months.
The procedure for sham injection was the same as that used for IVT injection until the actual injection but no actual injection occurred. | 212 |
| Total | 637 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 11 | 8 | 3 | 3 |
| Overall Study | Consent Withdrawal | 25 | 16 | 12 | 9 |
| Overall Study | Death | 20 | 9 | 7 | 1 |
| Overall Study | Due to Coronavirus Disease-2019 (COVID-19) impact | 9 | 4 | 5 | 8 |
| Overall Study | Lost to Follow-up | 4 | 5 | 3 | 2 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Pegcetacoplan Monthly | Pegcetacoplan EOM | Sham Pooled | Total |
|---|---|---|---|---|
| Age, Continuous | 79.0 years STANDARD_DEVIATION 7.21 | 78.1 years STANDARD_DEVIATION 7.81 | 78.6 years STANDARD_DEVIATION 7.2 | 78.6 years STANDARD_DEVIATION 7.41 |
| GA Lesion Size [fundus autofluorescence (FAF)] in the Study Eye | 8.2150 millimeter square (mm^2) STANDARD_DEVIATION 3.91483 | 8.3452 millimeter square (mm^2) STANDARD_DEVIATION 3.95679 | 8.1581 millimeter square (mm^2) STANDARD_DEVIATION 3.69739 | 8.2394 millimeter square (mm^2) STANDARD_DEVIATION 3.85283 |
| Race/Ethnicity, Customized Asian | 3 Participants | 1 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 5 Participants | 7 Participants | 4 Participants | 16 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 191 Participants | 193 Participants | 192 Participants | 576 Participants |
| Race/Ethnicity, Customized Not Reported | 17 Participants | 12 Participants | 16 Participants | 45 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 3 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 193 Participants | 196 Participants | 193 Participants | 582 Participants |
| Region of Enrollment Australia | 10 Participants | 14 Participants | 10 Participants | 34 Participants |
| Region of Enrollment Brazil | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Czechia | 9 Participants | 7 Participants | 5 Participants | 21 Participants |
| Region of Enrollment France | 15 Participants | 14 Participants | 15 Participants | 44 Participants |
| Region of Enrollment Germany | 7 Participants | 8 Participants | 11 Participants | 26 Participants |
| Region of Enrollment Israel | 3 Participants | 2 Participants | 1 Participants | 6 Participants |
| Region of Enrollment Italy | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Region of Enrollment Netherlands | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Region of Enrollment New Zealand | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Region of Enrollment Poland | 6 Participants | 5 Participants | 9 Participants | 20 Participants |
| Region of Enrollment Spain | 1 Participants | 3 Participants | 0 Participants | 4 Participants |
| Region of Enrollment United Kingdom | 2 Participants | 5 Participants | 4 Participants | 11 Participants |
| Region of Enrollment United States | 152 Participants | 148 Participants | 153 Participants | 453 Participants |
| Sex: Female, Male Female | 134 Participants | 122 Participants | 136 Participants | 392 Participants |
| Sex: Female, Male Male | 79 Participants | 90 Participants | 76 Participants | 245 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 213 | 0 / 212 | 0 / 211 | 0 / 213 | 0 / 212 | 0 / 211 | 20 / 213 | 9 / 212 | 8 / 211 |
| other Total, other adverse events | 100 / 213 | 95 / 212 | 59 / 211 | 69 / 213 | 56 / 212 | 65 / 211 | 86 / 213 | 72 / 212 | 67 / 211 |
| serious Total, serious adverse events | 5 / 213 | 4 / 212 | 1 / 211 | 1 / 213 | 0 / 212 | 2 / 211 | 77 / 213 | 56 / 212 | 55 / 211 |
Outcome results
Primary
Least Squares (LS) Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 12
The GA lesion area was measured by a quantified central reading center based on FAF images. LS mean was calculated using a mixed effect model for repeated measure (MMRM) model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
Time frame: Baseline (screening) and Month 12
Population: The modified intent-to-treat (mITT) analysis set included all subjects assigned to treatment who received at least 1 injection of pegcetacoplan or sham and had baseline and at least 1 post-baseline value of GA lesion area in the study eye as assessed by FAF. Subjects with a baseline and at least 1 post-baseline value of the outcome at a scheduled visit by Month 12 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan Monthly | Least Squares (LS) Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 12 | 1.5579 mm^2 | Standard Error 0.0835 |
| Pegcetacoplan EOM | Least Squares (LS) Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 12 | 1.6512 mm^2 | Standard Error 0.08118 |
| Sham Pooled | Least Squares (LS) Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 12 | 1.9692 mm^2 | Standard Error 0.08218 |
Comparison: Model included treatment + baseline GA lesion area (\<7.5 mm\^2 or ≥7.5 mm\^2) + analysis visit + presence of choroidal neovascularization (CNV) in the fellow eye (yes or no) + analysis visit × treatment + baseline GA lesion area × analysis visit.p-value: 0.000495% CI: [-0.6397, -0.1831]MMRM model
Comparison: Model included treatment + baseline GA lesion area (\<7.5 mm\^2 or ≥7.5 mm\^2) + analysis visit + presence of CNV in the fellow eye (yes or no) + analysis visit × treatment + baseline GA lesion area × analysis visit.p-value: 0.005595% CI: [-0.5423, -0.0937]MMRM model
Secondary
LS Mean Change From Baseline in Mean Functional Reading Independence (FRI) Index Score at Month 24
The FRI was an interviewer-administered questionnaire with 7 items on functional reading activities most relevant to GA AMD subjects. It had 1 total index score. For each FRI Index reading activity performed in the past 7 days, subjects were asked about the extent to which they required assistance beyond eyeglasses/contact lenses, including the use of low-vision aids, adjustments in the activity, or help from another subject. Mean FRI Index scores ranged from 1 (unable to do independently) to 4 (totally independent), with higher scores indicating higher functional reading independence. A negative change from baseline indicated a decrease in the FRI; disease worsening. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
Time frame: Baseline (screening) and Month 24
Population: The mITT analysis set included all subjects assigned to treatment who received at least 1 injection of pegcetacoplan or sham and had baseline and at least 1 post-baseline value of GA lesion area in the study eye as assessed by FAF. Subjects with a baseline and at least 1 post-baseline value of the outcome at a scheduled visit by Month 24 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan Monthly | LS Mean Change From Baseline in Mean Functional Reading Independence (FRI) Index Score at Month 24 | -0.287 score on a scale | Standard Error 0.0563 |
| Pegcetacoplan EOM | LS Mean Change From Baseline in Mean Functional Reading Independence (FRI) Index Score at Month 24 | -0.379 score on a scale | Standard Error 0.0536 |
| Sham Pooled | LS Mean Change From Baseline in Mean Functional Reading Independence (FRI) Index Score at Month 24 | -0.273 score on a scale | Standard Error 0.0554 |
Secondary
LS Mean Change From Baseline in Mean Threshold Sensitivity of All Points of the Study Eye at Month 24
Mean threshold sensitivity of all points was determined from the mesopic microperimetry as an assessment of the macular functional response. Microperimetry offers the option to test retinal light sensitivity while directly observing the fundus and allows for monitoring of macular function loss associated with GA progression. The microperimetry reading center overlaid the baseline FAF images with GA lesions traced by the imaging reading center and the corresponding macular integrity assessment microperimetry baseline scanning laser ophthalmoscope image and identified perilesional (within 500 microns outside the atrophy border), paralesional (beyond 500 microns outside the atrophy border), and extralesional (outside the atrophy border) loci on the microperimetry grid to determine the mean threshold sensitivity for these 3 areas. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
Time frame: Baseline (screening) and Month 24
Population: The mITT analysis set included all subjects assigned to treatment who received at least 1 injection of pegcetacoplan or sham and had baseline and at least 1 post-baseline value of GA lesion area in the study eye as assessed by FAF. Subjects with a baseline and at least 1 post-baseline value of the outcome at a scheduled visit by Month 24 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan Monthly | LS Mean Change From Baseline in Mean Threshold Sensitivity of All Points of the Study Eye at Month 24 | -3.319 decibels (dB) | Standard Error 0.2969 |
| Pegcetacoplan EOM | LS Mean Change From Baseline in Mean Threshold Sensitivity of All Points of the Study Eye at Month 24 | -3.064 decibels (dB) | Standard Error 0.2331 |
| Sham Pooled | LS Mean Change From Baseline in Mean Threshold Sensitivity of All Points of the Study Eye at Month 24 | -2.954 decibels (dB) | Standard Error 0.2156 |
Secondary
LS Mean Change From Baseline in Monocular Maximum Reading Speed of the Study Eye at Month 24
The maximum reading speed of the study eye was calculated per Minnesota Low-Vision Reading Test (MNREAD) or Radner Reading Charts user manuals, with no adjustment for reading inaccuracy. An additional step to cap resulting reading speed values at a maximum of 300 words per minute (wpm) was implemented. Maximum reading speed was calculated as the mean of the 3 highest non-zero reading speeds (or 2, or 1 value, as available), except when all wpm were calculated as 0 then the maximum reading speed was calculated as 0. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
Time frame: Baseline (screening) and Month 24
Population: The mITT analysis set included all subjects assigned to treatment who received at least 1 injection of pegcetacoplan or sham and had baseline and at least 1 post-baseline value of GA lesion area in the study eye as assessed by FAF. Subjects with a baseline and at least 1 post-baseline value of the outcome at a scheduled visit by Month 24 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan Monthly | LS Mean Change From Baseline in Monocular Maximum Reading Speed of the Study Eye at Month 24 | -22.446 wpm | Standard Error 3.0329 |
| Pegcetacoplan EOM | LS Mean Change From Baseline in Monocular Maximum Reading Speed of the Study Eye at Month 24 | -17.533 wpm | Standard Error 3.2886 |
| Sham Pooled | LS Mean Change From Baseline in Monocular Maximum Reading Speed of the Study Eye at Month 24 | -16.211 wpm | Standard Error 3.8129 |
Secondary
LS Mean Change From Baseline in Normal-Luminance Best-Corrected Visual Acuity (NL-BCVA) Score of the Study Eye at Month 24
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 positive change in the value indicated improvement in visual acuity. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
Time frame: Baseline (screening) and Month 24
Population: The mITT analysis set included all subjects assigned to treatment who received at least 1 injection of pegcetacoplan or sham and had baseline and at least 1 post-baseline value of GA lesion area in the study eye as assessed by FAF. Subjects with a baseline and at least 1 post-baseline value of the outcome at a scheduled visit by Month 24 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan Monthly | LS Mean Change From Baseline in Normal-Luminance Best-Corrected Visual Acuity (NL-BCVA) Score of the Study Eye at Month 24 | -7.477 ETDRS letters score | Standard Error 1.0512 |
| Pegcetacoplan EOM | LS Mean Change From Baseline in Normal-Luminance Best-Corrected Visual Acuity (NL-BCVA) Score of the Study Eye at Month 24 | -8.526 ETDRS letters score | Standard Error 1.0525 |
| Sham Pooled | LS Mean Change From Baseline in Normal-Luminance Best-Corrected Visual Acuity (NL-BCVA) Score of the Study Eye at Month 24 | -7.660 ETDRS letters score | Standard Error 1.0734 |
Secondary
LS Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 24
The GA lesion area was measured by a quantified central reading center based on FAF images. LS mean was calculated using a mixed effect model for repeated measure model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
Time frame: Baseline (screening) and Month 24
Population: The mITT analysis set included all subjects assigned to treatment who received at least 1 injection of pegcetacoplan or sham and had baseline and at least 1 post-baseline value of GA lesion area in the study eye as assessed by FAF. Subjects with a baseline and at least 1 post-baseline value of the outcome at a scheduled visit by Month 24 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan Monthly | LS Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 24 | 3.1237 mm^2 | Standard Error 0.14327 |
| Pegcetacoplan EOM | LS Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 24 | 3.2826 mm^2 | Standard Error 0.13238 |
| Sham Pooled | LS Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 24 | 4.0252 mm^2 | Standard Error 0.14642 |
Comparison: Model included treatment + baseline GA lesion area (\<7.5 mm\^2 or ≥7.5 mm\^2) + analysis visit + baseline presence of CNV in the fellow eye (yes or no) + analysis visit × treatment + baseline GA lesion area (\<7.5 mm\^2 or ≥7.5 mm\^2) × analysis visit.p-value: <0.000195% CI: [-1.3026, -0.5004]MMRM model
Comparison: Model included treatment + baseline GA lesion area (\<7.5 mm\^2 or ≥7.5 mm\^2) + analysis visit + baseline presence of CNV in the fellow eye (yes or no) + analysis visit × treatment + baseline GA lesion area (\<7.5 mm\^2 or ≥7.5 mm\^2) × analysis visit.p-value: 0.000295% CI: [-1.1282, -0.357]MMRM model
Secondary
Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24
The mean change in GA lesion area through Month 24 was measured by assuming a piecewise linear trend in time with knots by FAF images at Months 6, 12, 18, and 24 and was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
Time frame: From Baseline (screening) through Month 24
Population: The mITT analysis set included all subjects assigned to treatment who received at least 1 injection of pegcetacoplan or sham and had baseline and at least 1 post-baseline value of GA lesion area in the study eye as assessed by FAF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pegcetacoplan Monthly | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Month 18 to Month 24 | 0.7617 mm^2 | Standard Error 0.665 |
| Pegcetacoplan Monthly | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Month 12 to Month 18 | 0.8004 mm^2 | Standard Error 0.05034 |
| Pegcetacoplan Monthly | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Baseline to Month 6 | 0.7604 mm^2 | Standard Error 0.04629 |
| Pegcetacoplan Monthly | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Month 6 to Month 12 | 0.7848 mm^2 | Standard Error 0.05958 |
| Pegcetacoplan Monthly | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Baseline to Month 24 | 3.1073 mm^2 | Standard Error 0.14841 |
| Pegcetacoplan EOM | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Month 12 to Month 18 | 0.8682 mm^2 | Standard Error 0.04959 |
| Pegcetacoplan EOM | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Baseline to Month 6 | 0.8220 mm^2 | Standard Error 0.04346 |
| Pegcetacoplan EOM | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Month 6 to Month 12 | 0.8184 mm^2 | Standard Error 0.0566 |
| Pegcetacoplan EOM | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Month 18 to Month 24 | 0.7499 mm^2 | Standard Error 0.04372 |
| Pegcetacoplan EOM | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Baseline to Month 24 | 3.2586 mm^2 | Standard Error 0.1342 |
| Sham Pooled | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Baseline to Month 24 | 3.9775 mm^2 | Standard Error 0.1431 |
| Sham Pooled | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Month 18 to Month 24 | 0.9958 mm^2 | Standard Error 0.05824 |
| Sham Pooled | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Baseline to Month 6 | 0.9838 mm^2 | Standard Error 0.04666 |
| Sham Pooled | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Month 12 to Month 18 | 1.0269 mm^2 | Standard Error 0.05288 |
| Sham Pooled | Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 | From Month 6 to Month 12 | 0.9710 mm^2 | Standard Error 0.05163 |
Comparison: Estimates for Baseline to Month 6: Model included Treatment + Baseline GA lesion area (\< 7.5 mm\^2 or \>= 7.5 mm\^2) + Time (continuous) + Time Spline at Month 6 (continuous) + Time Spline at Month 12 (continuous) + Time Spline at Month 18 (continuous) + Presence of CNV in the fellow eye (Yes or No) + Time (continuous) x Treatment + Time Spline at Month 6 (continuous) x Treatment + Time Spline at Month 12 (continuous) x Treatment + Time Spline at Month 18 (continuous) x Treatment +p-value: 0.000795% CI: [-0.3522, -0.0946]MMRM model
Comparison: Estimates for Baseline to Month 6: Model included Treatment + Baseline GA lesion area (\< 7.5 mm\^2 or \>= 7.5 mm\^2) + Time (continuous) + Time Spline at Month 6 (continuous) + Time Spline at Month 12 (continuous) + Time Spline at Month 18 (continuous) + Presence of CNV in the fellow eye (Yes or No) + Time (continuous) x Treatment + Time Spline at Month 6 (continuous) x Treatment + Time Spline at Month 12 (continuous) x Treatment + Time Spline at Month 18 (continuous) x Treatment +p-value: 0.011695% CI: [-0.2874, -0.0361]MMRM model
Comparison: Estimates for Month 6 to Month 12: Model included Treatment + Baseline GA lesion area (\< 7.5 mm\^2 or \>= 7.5 mm\^2) + Time (continuous) + Time Spline at Month 6 (continuous) + Time Spline at Month 12 (continuous) + Time Spline at Month 18 (continuous) + Presence of CNV in the fellow eye (Yes or No) + Time (continuous) x Treatment + Time Spline at Month 6 (continuous) x Treatment + Time Spline at Month 12 (continuous) x Treatment + Time Spline at Month 18 (continuous) x Treatment +p-value: 0.018195% CI: [-0.3406, -0.0318]MMRM model
Comparison: Estimates for Month 6 to Month 12: Model included Treatment + Baseline GA lesion area (\< 7.5 mm\^2 or \>= 7.5 mm\^2) + Time (continuous) + Time Spline at Month 6 (continuous) + Time Spline at Month 12 (continuous) + Time Spline at Month 18 (continuous) + Presence of CNV in the fellow eye (Yes or No) + Time (continuous) x Treatment + Time Spline at Month 6 (continuous) x Treatment + Time Spline at Month 12 (continuous) x Treatment + Time Spline at Month 18 (continuous) x Treatment +p-value: 0.046795% CI: [-0.303, -0.0023]MMRM model
Comparison: Estimates for Month 12 to Month 18: Model included Treatment + Baseline GA lesion area (\< 7.5 mm\^2 or \>= 7.5 mm\^2) + Time (continuous) + Time Spline at Month 6 (continuous) + Time Spline at Month 12 (continuous) + Time Spline at Month 18 (continuous) + Presence of CNV in the fellow eye (Yes or No) + Time (continuous) x Treatment + Time Spline at Month 6 (continuous) x Treatment + Time Spline at Month 12 (continuous) x Treatment + Time Spline at Month 18 (continuous) x Treatment +p-value: 0.001995% CI: [-0.3696, -0.0834]MMRM model
Comparison: Estimates for Month 12 to Month 18: Model included Treatment + Baseline GA lesion area (\< 7.5 mm\^2 or \>= 7.5 mm\^2) + Time (continuous) + Time Spline at Month 6 (continuous) + Time Spline at Month 12 (continuous) + Time Spline at Month 18 (continuous) + Presence of CNV in the fellow eye (Yes or No) + Time (continuous) x Treatment + Time Spline at Month 6 (continuous) x Treatment + Time Spline at Month 12 (continuous) x Treatment + Time Spline at Month 18 (continuous) x Treatment +p-value: 0.028895% CI: [-0.3009, -0.0164]MMRM model
Comparison: Estimates for Month 18 to Month 24: Model included Treatment + Baseline GA lesion area (\< 7.5 mm\^2 or \>= 7.5 mm\^2) + Time (continuous) + Time Spline at Month 6 (continuous) + Time Spline at Month 12 (continuous) + Time Spline at Month 18 (continuous) + Presence of CNV in the fellow eye (Yes or No) + Time (continuous) x Treatment + Time Spline at Month 6 (continuous) x Treatment + Time Spline at Month 12 (continuous) x Treatment + Time Spline at Month 18 (continuous) x Treatment +p-value: 0.00895% CI: [-0.4071, -0.0611]MMRM model
Comparison: Estimates for Month 18 to Month 24: Model included Treatment + Baseline GA lesion area (\< 7.5 mm\^2 or \>= 7.5 mm\^2) + Time (continuous) + Time Spline at Month 6 (continuous) + Time Spline at Month 12 (continuous) + Time Spline at Month 18 (continuous) + Presence of CNV in the fellow eye (Yes or No) + Time (continuous) x Treatment + Time Spline at Month 6 (continuous) x Treatment + Time Spline at Month 12 (continuous) x Treatment + Time Spline at Month 18 (continuous) x Treatment +p-value: 0.000795% CI: [-0.3886, -0.1031]MMRM model
Comparison: Estimates for Baseline to Month 24: Model included Treatment + Baseline GA lesion area (\< 7.5 mm\^2 or \>= 7.5 mm\^2) + Time (continuous) + Time Spline at Month 6 (continuous) + Time Spline at Month 12 (continuous) + Time Spline at Month 18 (continuous) + Presence of CNV in the fellow eye (Yes or No) + Time (continuous) x Treatment + Time Spline at Month 6 (continuous) x Treatment + Time Spline at Month 12 (continuous) x Treatment + Time Spline at Month 18 (continuous) x Treatment +p-value: <0.000195% CI: [-1.274, -0.4664]MMRM model
Comparison: Estimates for Baseline to Month 24: Model included Treatment + Baseline GA lesion area (\< 7.5 mm\^2 or \>= 7.5 mm\^2) + Time (continuous) + Time Spline at Month 6 (continuous) + Time Spline at Month 12 (continuous) + Time Spline at Month 18 (continuous) + Presence of CNV in the fellow eye (Yes or No) + Time (continuous) x Treatment + Time Spline at Month 6 (continuous) x Treatment + Time Spline at Month 12 (continuous) x Treatment + Time Spline at Month 18 (continuous) x Treatment +p-value: 0.000395% CI: [-1.1039, -0.3339]MMRM model