A Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration

• ClinicalTrials.gov Identifier: NCT03525613
• Recruitment Status: Completed
• First Posted: May 15, 2018
• Results First Posted: July 6, 2023
• Last Update Posted: July 6, 2023
• Sponsor: Apellis Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Apellis Pharmaceuticals, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Geographic Atrophy
• Interventions: Drug: APL-2; Other: Sham Procedure
• Enrollment: 637

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.

Arm/Group Title	Pegcetacoplan Monthly	Pegcetacoplan EOM	Sham Monthly	Sham EOM
Arm/Group Description	Subjects received intravitreal (IVT) injections of pegcetacoplan 15 milligram (mg)/0.1 milliliter (mL) once monthly for 24 months.	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL EOM for 24 months.	Subjects received sham injections once monthly 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.	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.
Period Title: Overall Study
Started	213	212	106	106
Completed	144	169	76	82
Not Completed	69	43	30	24
Reason Not Completed
Adverse Event	11	8	3	3
Lost to Follow-up	4	5	3	2
Physician Decision	0	1	0	1
Consent Withdrawal	25	16	12	9
Death	20	9	7	1
Due to Coronavirus Disease-2019 (COVID-19) impact	9	4	5	8

Baseline Characteristics

Arm/Group Title		Pegcetacoplan Monthly	Pegcetacoplan EOM	Sham Pooled	Total
Arm/Group Description		Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL once monthly for 24 months.	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL EOM for 24 months.	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.	Total of all reporting groups
Overall Number of Baseline Participants		213	212	212	637
Baseline Analysis Population Description		The intent-to-treat (ITT) analysis set included all subjects assigned to treatment.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	213 participants	212 participants	212 participants	637 participants
		79.0 (7.21)	78.1 (7.81)	78.6 (7.20)	78.6 (7.41)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	213 participants	212 participants	212 participants	637 participants
	Female	134	122	136	392
	Male	79	90	76	245
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	213 participants	212 participants	212 participants	637 participants
White		193	196	193	582
Not Reported		14	12	14	40
Unknown		1	3	3	7
Asian		3	1	2	6
Black or African American		2	0	0	2
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	213 participants	212 participants	212 participants	637 participants
Hispanic or Latino		5	7	4	16
Not Hispanic or Latino		191	193	192	576
Not Reported		17	12	16	45
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	213 participants	212 participants	212 participants	637 participants
United States		152	148	153	453
France		15	14	15	44
Australia		10	14	10	34
Germany		7	8	11	26
Czechia		9	7	5	21
Poland		6	5	9	20
United Kingdom		2	5	4	11
Italy		3	3	3	9
Israel		3	2	1	6
Netherlands		3	1	0	4
New Zealand		1	2	1	4
Spain		1	3	0	4
Brazil		1	0	0	1
GA Lesion Size [fundus autofluorescence (FAF)] in the Study Eye; Mean (Standard Deviation); Unit of measure: Millimeter square (mm^2)
	Number Analyzed	213 participants	212 participants	212 participants	637 participants
		8.2150 (3.91483)	8.3452 (3.95679)	8.1581 (3.69739)	8.2394 (3.85283)

Outcome Measures

1. Primary Outcome

Title	Least Squares (LS) Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 12
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Pegcetacoplan Monthly	Pegcetacoplan EOM	Sham Pooled
Arm/Group Description:	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL once monthly for 24 months.	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL EOM for 24 months.	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.
Overall Number of Participants Analyzed	202	204	205
Least Squares Mean (Standard Error); Unit of Measure: mm^2
	1.5579 (0.08350)	1.6512 (0.08118)	1.9692 (0.08218)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pegcetacoplan Monthly, Sham Pooled
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0004
	Comments	[Not Specified]
	Method	MMRM model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4114
	Confidence Interval	(2-Sided) 95%; -0.6397 to -0.1831
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pegcetacoplan EOM, Sham Pooled
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0055
	Comments	[Not Specified]
	Method	MMRM model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3180
	Confidence Interval	(2-Sided) 95%; -0.5423 to -0.0937
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	LS Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 24
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Pegcetacoplan Monthly	Pegcetacoplan EOM	Sham Pooled
Arm/Group Description:	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL once monthly for 24 months.	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL EOM for 24 months.	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.
Overall Number of Participants Analyzed	202	204	206
Least Squares Mean (Standard Error); Unit of Measure: mm^2
	3.1237 (0.14327)	3.2826 (0.13238)	4.0252 (0.14642)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pegcetacoplan Monthly, Sham Pooled
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	MMRM model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.9015
	Confidence Interval	(2-Sided) 95%; -1.3026 to -0.5004
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pegcetacoplan EOM, Sham Pooled
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0002
	Comments	[Not Specified]
	Method	MMRM model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7426
	Confidence Interval	(2-Sided) 95%; -1.1282 to -0.3570
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Pegcetacoplan Monthly	Pegcetacoplan EOM	Sham Pooled
Arm/Group Description:	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL once monthly for 24 months.	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL EOM for 24 months.	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.
Overall Number of Participants Analyzed	202	205	207
Mean (Standard Error); Unit of Measure: mm^2
From Baseline to Month 6	0.7604 (0.04629)	0.8220 (0.04346)	0.9838 (0.04666)
From Month 6 to Month 12	0.7848 (0.05958)	0.8184 (0.05660)	0.9710 (0.05163)
From Month 12 to Month 18	0.8004 (0.05034)	0.8682 (0.04959)	1.0269 (0.05288)
From Month 18 to Month 24	0.7617 (0.6650)	0.7499 (0.04372)	0.9958 (0.05824)
From Baseline to Month 24	3.1073 (0.14841)	3.2586 (0.13420)	3.9775 (0.14310)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pegcetacoplan Monthly, Sham Pooled
	Comments	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 +
	Type of Statistical Test	Superiority
	Comments	Baseline GA lesion area x Time (continuous) + Baseline GA lesion area x Time Spline at Month 6 (continuous) + Baseline GA lesion area x Time Spline at Month 12 (continuous) + Baseline GA lesion area x Time Spline at Month 18 (continuous). A heterogeneous autoregressive covariance matrix was used to model within-subject errors.
Statistical Test of Hypothesis	P-Value	0.0007
	Comments	[Not Specified]
	Method	MMRM model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.2234
	Confidence Interval	(2-Sided) 95%; -0.3522 to -0.0946
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pegcetacoplan EOM, Sham Pooled
	Comments	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 +
	Type of Statistical Test	Superiority
	Comments	Baseline GA lesion area x Time (continuous) + Baseline GA lesion area x Time Spline at Month 6 (continuous) + Baseline GA lesion area x Time Spline at Month 12 (continuous) + Baseline GA lesion area x Time Spline at Month 18 (continuous). A heterogeneous autoregressive covariance matrix was used to model within-subject errors.
Statistical Test of Hypothesis	P-Value	0.0116
	Comments	[Not Specified]
	Method	MMRM model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.1618
	Confidence Interval	(2-Sided) 95%; -0.2874 to -0.0361
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pegcetacoplan Monthly, Sham Pooled
	Comments	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 +
	Type of Statistical Test	Superiority
	Comments	Baseline GA lesion area x Time (continuous) + Baseline GA lesion area x Time Spline at Month 6 (continuous) + Baseline GA lesion area x Time Spline at Month 12 (continuous) + Baseline GA lesion area x Time Spline at Month 18 (continuous). A heterogeneous autoregressive covariance matrix was used to model within-subject errors.
Statistical Test of Hypothesis	P-Value	0.0181
	Comments	[Not Specified]
	Method	MMRM model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.1862
	Confidence Interval	(2-Sided) 95%; -0.3406 to -0.0318
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pegcetacoplan EOM, Sham Pooled
	Comments	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 +
	Type of Statistical Test	Superiority
	Comments	Baseline GA lesion area x Time (continuous) + Baseline GA lesion area x Time Spline at Month 6 (continuous) + Baseline GA lesion area x Time Spline at Month 12 (continuous) + Baseline GA lesion area x Time Spline at Month 18 (continuous). A heterogeneous autoregressive covariance matrix was used to model within-subject errors.
Statistical Test of Hypothesis	P-Value	0.0467
	Comments	[Not Specified]
	Method	MMRM model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.1526
	Confidence Interval	(2-Sided) 95%; -0.3030 to -0.0023
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pegcetacoplan Monthly, Sham Pooled
	Comments	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 +
	Type of Statistical Test	Superiority
	Comments	Baseline GA lesion area x Time (continuous) + Baseline GA lesion area x Time Spline at Month 6 (continuous) + Baseline GA lesion area x Time Spline at Month 12 (continuous) + Baseline GA lesion area x Time Spline at Month 18 (continuous). A heterogeneous autoregressive covariance matrix was used to model within-subject errors.
Statistical Test of Hypothesis	P-Value	0.0019
	Comments	[Not Specified]
	Method	MMRM model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.2265
	Confidence Interval	(2-Sided) 95%; -0.3696 to -0.0834
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pegcetacoplan EOM, Sham Pooled
	Comments	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 +
	Type of Statistical Test	Superiority
	Comments	Baseline GA lesion area x Time (continuous) + Baseline GA lesion area x Time Spline at Month 6 (continuous) + Baseline GA lesion area x Time Spline at Month 12 (continuous) + Baseline GA lesion area x Time Spline at Month 18 (continuous). A heterogeneous autoregressive covariance matrix was used to model within-subject errors.
Statistical Test of Hypothesis	P-Value	0.0288
	Comments	[Not Specified]
	Method	MMRM model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.1586
	Confidence Interval	(2-Sided) 95%; -0.3009 to -0.0164
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Pegcetacoplan Monthly, Sham Pooled
	Comments	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 +
	Type of Statistical Test	Superiority
	Comments	Baseline GA lesion area x Time (continuous) + Baseline GA lesion area x Time Spline at Month 6 (continuous) + Baseline GA lesion area x Time Spline at Month 12 (continuous) + Baseline GA lesion area x Time Spline at Month 18 (continuous). A heterogeneous autoregressive covariance matrix was used to model within-subject errors.
Statistical Test of Hypothesis	P-Value	0.0080
	Comments	[Not Specified]
	Method	MMRM model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.2341
	Confidence Interval	(2-Sided) 95%; -0.4071 to -0.0611
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Pegcetacoplan EOM, Sham Pooled
	Comments	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 +
	Type of Statistical Test	Superiority
	Comments	Baseline GA lesion area x Time (continuous) + Baseline GA lesion area x Time Spline at Month 6 (continuous) + Baseline GA lesion area x Time Spline at Month 12 (continuous) + Baseline GA lesion area x Time Spline at Month 18 (continuous). A heterogeneous autoregressive covariance matrix was used to model within-subject errors.
Statistical Test of Hypothesis	P-Value	0.0007
	Comments	[Not Specified]
	Method	MMRM model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.2459
	Confidence Interval	(2-Sided) 95%; -0.3886 to -0.1031
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Pegcetacoplan Monthly, Sham Pooled
	Comments	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 +
	Type of Statistical Test	Superiority
	Comments	Baseline GA lesion area x Time (continuous) + Baseline GA lesion area x Time Spline at Month 6 (continuous) + Baseline GA lesion area x Time Spline at Month 12 (continuous) + Baseline GA lesion area x Time Spline at Month 18 (continuous). A heterogeneous autoregressive covariance matrix was used to model within-subject errors.
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	MMRM model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.8702
	Confidence Interval	(2-Sided) 95%; -1.2740 to -0.4664
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Pegcetacoplan EOM, Sham Pooled
	Comments	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 +
	Type of Statistical Test	Superiority
	Comments	Baseline GA lesion area x Time (continuous) + Baseline GA lesion area x Time Spline at Month 6 (continuous) + Baseline GA lesion area x Time Spline at Month 12 (continuous) + Baseline GA lesion area x Time Spline at Month 18 (continuous). A heterogeneous autoregressive covariance matrix was used to model within-subject errors.
Statistical Test of Hypothesis	P-Value	0.0003
	Comments	[Not Specified]
	Method	MMRM model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.7189
	Confidence Interval	(2-Sided) 95%; -1.1039 to -0.3339
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	LS Mean Change From Baseline in Mean Threshold Sensitivity of All Points of the Study Eye at Month 24
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Pegcetacoplan Monthly	Pegcetacoplan EOM	Sham Pooled
Arm/Group Description:	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL once monthly for 24 months.	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL EOM for 24 months.	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.
Overall Number of Participants Analyzed	179	187	186
Least Squares Mean (Standard Error); Unit of Measure: decibels (dB)
	-3.319 (0.2969)	-3.064 (0.2331)	-2.954 (0.2156)

5. Secondary Outcome

Title	LS Mean Change From Baseline in Monocular Maximum Reading Speed of the Study Eye at Month 24
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Pegcetacoplan Monthly	Pegcetacoplan EOM	Sham Pooled
Arm/Group Description:	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL once monthly for 24 months.	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL EOM for 24 months.	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.
Overall Number of Participants Analyzed	168	181	181
Least Squares Mean (Standard Error); Unit of Measure: wpm
	-22.446 (3.0329)	-17.533 (3.2886)	-16.211 (3.8129)

6. Secondary Outcome

Title	LS Mean Change From Baseline in Mean Functional Reading Independence (FRI) Index Score at Month 24
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Pegcetacoplan Monthly	Pegcetacoplan EOM	Sham Pooled
Arm/Group Description:	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL once monthly for 24 months.	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL EOM for 24 months.	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.
Overall Number of Participants Analyzed	185	193	195
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-0.287 (0.0563)	-0.379 (0.0536)	-0.273 (0.0554)

7. Secondary Outcome

Title	LS Mean Change From Baseline in Normal-Luminance Best-Corrected Visual Acuity (NL-BCVA) Score of the Study Eye at Month 24
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Pegcetacoplan Monthly	Pegcetacoplan EOM	Sham Pooled
Arm/Group Description:	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL once monthly for 24 months.	Subjects received IVT injections of pegcetacoplan 15 mg/0.1 mL EOM for 24 months.	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.
Overall Number of Participants Analyzed	202	205	207
Least Squares Mean (Standard Error); Unit of Measure: ETDRS letters score
	-7.477 (1.0512)	-8.526 (1.0525)	-7.660 (1.0734)

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) were reported from first study drug administration (Day 1) up to the last visit or early termination visit, 30 days after the last study drug administration for the monthly treatment groups and 60 days after the last study drug administration for the EOM treatment groups, a maximum of 24 months.
Adverse Event Reporting Description	The safety analysis set included all subjects randomly assigned to treatment who received at least 1 injection of pegcetacoplan or sham. Ocular TEAEs are presented separately for the study and fellow eyes, and non-ocular (systemic) TEAEs are also presented.
Arm/Group Title	Pegcetacoplan Monthly: Ocular Study Eye		Pegcetacoplan EOM: Ocular Study Eye		Sham Pooled: Ocular Study Eye		Pegcetacoplan Monthly: Ocular Fellow Eye		Pegcetacoplan EOM: Ocular Fellow Eye		Sham Pooled: Ocular Fellow Eye		Pegcetacoplan Monthly: Non-ocular		Pegcetacoplan EOM: Non-ocular		Sham Pooled: Non-ocular
Arm/Group Description	Ocular TEAEs were summarized for the study eye for all subjects who received IVT injections of pegcetacoplan 15 mg/0.1 mL once monthly for 24 months.		Ocular TEAEs were summarized for the study eye for all subjects who received IVT injections of pegcetacoplan 15 mg/0.1 mL EOM for 24 months.		Ocular TEAEs were summarized for the study eye for all subjects who were randomized to sham monthly and sham EOM treatment groups. 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.		Ocular TEAEs were summarized for the fellow eye for all subjects who received IVT injections of pegcetacoplan 15 mg/0.1 mL once monthly for 24 months.		Ocular TEAEs were summarized for the fellow eye for all subjects who received IVT injections of pegcetacoplan 15 mg/0.1 mL EOM for 24 months.		Ocular TEAEs were summarized for the fellow eye for all subjects who were randomized to sham monthly and sham EOM treatment groups. 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.		Non-ocular (systemic) TEAEs were summarized for all subjects who received IVT injections of pegcetacoplan 15 mg/0.1 mL once monthly for 24 months.		Non-ocular (systemic) TEAEs were summarized for all subjects who received IVT injections of pegcetacoplan 15 mg/0.1 mL EOM for 24 months.		Non-ocular (systemic) TEAEs were summarized for all subjects who were randomized to sham monthly and sham EOM treatment groups. 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.
All-Cause Mortality
	Pegcetacoplan Monthly: Ocular Study Eye		Pegcetacoplan EOM: Ocular Study Eye		Sham Pooled: Ocular Study Eye		Pegcetacoplan Monthly: Ocular Fellow Eye		Pegcetacoplan EOM: Ocular Fellow Eye		Sham Pooled: Ocular Fellow Eye		Pegcetacoplan Monthly: Non-ocular		Pegcetacoplan EOM: Non-ocular		Sham Pooled: Non-ocular
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/213 (0.00%)		0/212 (0.00%)		0/211 (0.00%)		0/213 (0.00%)		0/212 (0.00%)		0/211 (0.00%)		20/213 (9.39%)		9/212 (4.25%)		8/211 (3.79%)
Serious Adverse Events
	Pegcetacoplan Monthly: Ocular Study Eye		Pegcetacoplan EOM: Ocular Study Eye		Sham Pooled: Ocular Study Eye		Pegcetacoplan Monthly: Ocular Fellow Eye		Pegcetacoplan EOM: Ocular Fellow Eye		Sham Pooled: Ocular Fellow Eye		Pegcetacoplan Monthly: Non-ocular		Pegcetacoplan EOM: Non-ocular		Sham Pooled: Non-ocular
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/213 (2.35%)		4/212 (1.89%)		1/211 (0.47%)		1/213 (0.47%)		0/212 (0.00%)		2/211 (0.95%)		77/213 (36.15%)		56/212 (26.42%)		55/211 (26.07%)
Blood and lymphatic system disorders
Blood loss anaemia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	1/211 (0.47%)	1
Lymphadenopathy † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Splenic infarction † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Anaemia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Cardiac disorders
Atrial fibrillation † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	7/213 (3.29%)	8	1/212 (0.47%)	1	6/211 (2.84%)	6
Cardiac failure congestive † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	3/213 (1.41%)	5	3/212 (1.42%)	3	3/211 (1.42%)	3
Acute myocardial infarction † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	2/212 (0.94%)	2	0/211 (0.00%)	0
Angina pectoris † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	1/212 (0.47%)	1	0/211 (0.00%)	0
Cardiac arrest † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	1/212 (0.47%)	1	0/211 (0.00%)	0
Cardiac failure † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	1/212 (0.47%)	1	0/211 (0.00%)	0
Myocardial infarction † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	2/213 (0.94%)	2	0/212 (0.00%)	0	2/211 (0.95%)	2
Arrhythmia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Cardiac failure acute † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Cardiogenic shock † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Coronary artery disease † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	1/211 (0.47%)	1
Coronary artery stenosis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Mitral valve incompetence † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Myocardial ischaemia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Sinus node dysfunction † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Supraventricular extrasystoles † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Supraventricular tachycardia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Coronary artery occlusion † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Right ventricular failure † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Ear and labyrinth disorders
Vertigo positional † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Eye disorders
Optic ischaemic neuropathy † 1	2/213 (0.94%)	2	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Retinal detachment † 1	1/213 (0.47%)	1	1/212 (0.47%)	1	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Papilloedema † 1	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Visual acuity reduced † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	1/212 (0.47%)	1	0/211 (0.00%)	0
Colitis ulcerative † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	1/212 (0.47%)	1	0/211 (0.00%)	0
Gastrointestinal haemorrhage † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	2/213 (0.94%)	2	0/212 (0.00%)	0	1/211 (0.47%)	1
Abdominal hernia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Ascites † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Colitis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	1/211 (0.47%)	1
Gastric ulcer † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Intestinal perforation † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Large intestine polyp † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Peptic ulcer haemorrhage † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Small intestinal obstruction † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Diverticular perforation † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Duodenal ulcer haemorrhage † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Hypoaesthesia oral † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Inguinal hernia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Intestinal haemorrhage † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Intestinal ischaemia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Oesophagitis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
General disorders
Death † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	2/213 (0.94%)	2	1/212 (0.47%)	1	1/211 (0.47%)	1
General physical health deterioration † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	2/212 (0.94%)	2	0/211 (0.00%)	0
Disease complication † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Multiple organ dysfunction syndrome † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Asthenia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Chest discomfort † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Sudden death † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Hepatobiliary disorders
Cholangitis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	2	0/211 (0.00%)	0
Cholecystitis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Cholelithiasis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Cirrhosis alcoholic † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Hepatic failure † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Infections and infestations
Endophthalmitis † 1	2/213 (0.94%)	2	3/212 (1.42%)	3	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	2/211 (0.95%)	2	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Pneumonia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	12/213 (5.63%)	12	3/212 (1.42%)	3	3/211 (1.42%)	4
COVID-19 † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	7/213 (3.29%)	7	3/212 (1.42%)	3	4/211 (1.90%)	4
COVID-19 pneumonia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	2/213 (0.94%)	2	1/212 (0.47%)	1	4/211 (1.90%)	5
Septic shock † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	3/212 (1.42%)	3	0/211 (0.00%)	0
Cellulitis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	1/212 (0.47%)	1	2/211 (0.95%)	2
Sepsis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	2/213 (0.94%)	2	0/212 (0.00%)	0	0/211 (0.00%)	0
Acute sinusitis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Bacteraemia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Bronchiolitis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Clostridium difficile infection † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Diverticulitis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Enterococcal bacteraemia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	2	0/212 (0.00%)	0	0/211 (0.00%)	0
Influenza † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	1/211 (0.47%)	1
Klebsiella bacteraemia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Post procedural infection † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Postoperative wound infection † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Pyelonephritis acute † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Respiratory tract infection † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Urinary tract infection † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	2/211 (0.95%)	2
Arthritis infective † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Blastocystis infection † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Bronchitis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Bronchitis bacterial † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Localised infection † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Pneumonia bacterial † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Urosepsis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Injury, poisoning and procedural complications
Hyphaema † 1	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Rib fracture † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	3/212 (1.42%)	3	0/211 (0.00%)	0
Road traffic accident † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	2/213 (0.94%)	2	1/212 (0.47%)	1	1/211 (0.47%)	1
Subdural haematoma † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	2/213 (0.94%)	2	1/212 (0.47%)	1	1/211 (0.47%)	1
Ankle fracture † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	1/212 (0.47%)	1	0/211 (0.00%)	0
Head injury † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	2/212 (0.94%)	2	0/211 (0.00%)	0
Hip fracture † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	2/212 (0.94%)	2	1/211 (0.47%)	1
Anaemia postoperative † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	2	0/211 (0.00%)	0
Cervical vertebral fracture † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	2	0/212 (0.00%)	0	0/211 (0.00%)	0
Fall † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	1/211 (0.47%)	1
Femur fracture † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	1/211 (0.47%)	1
Jaw fracture † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Joint dislocation † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Lower limb fracture † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Meniscus injury † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Multiple injuries † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Muscle strain † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Pelvic fracture † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Post procedural haematuria † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	2	0/211 (0.00%)	0
Postoperative thrombosis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	2	0/211 (0.00%)	0
Procedural pain † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Sternal fracture † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Subcutaneous haematoma † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Urinary retention postoperative † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	2	0/211 (0.00%)	0
Face injury † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Spinal compression fracture † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Splenic rupture † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Upper limb fracture † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	2/211 (0.95%)	2
Investigations
Haemoglobin decreased † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Metabolism and nutrition disorders
Malnutrition † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	1/212 (0.47%)	1	0/211 (0.00%)	0
Dehydration † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Hypernatraemia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Hyponatraemia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Decreased appetite † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Hyperkalaemia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Hypoglycaemia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Hypokalaemia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	2/211 (0.95%)	2
Musculoskeletal and connective tissue disorders
Osteoarthritis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	1/212 (0.47%)	1	1/211 (0.47%)	1
Intervertebral disc protrusion † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Pain in jaw † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Rheumatoid arthritis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Rotator cuff syndrome † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Spinal stenosis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	1/211 (0.47%)	1
Synovial cyst † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Pain in extremity † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	2/213 (0.94%)	2	0/212 (0.00%)	0	0/211 (0.00%)	0
Basal cell carcinoma † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	1/212 (0.47%)	1	0/211 (0.00%)	0
Chronic myeloid leukaemia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	1/212 (0.47%)	1	0/211 (0.00%)	0
Skin cancer † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	2/213 (0.94%)	2	0/212 (0.00%)	0	0/211 (0.00%)	0
Anal squamous cell carcinoma † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Benign lung neoplasm † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Breast cancer † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Colon cancer † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	1/211 (0.47%)	1
Endometrial cancer † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Fibrosarcoma † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Lung neoplasm malignant † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Lymphoma † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Malignant melanoma † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Non-small cell lung cancer † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Ovarian cancer † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Pancreatic carcinoma metastatic † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Prostate cancer † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	1/211 (0.47%)	1
Urethral cancer † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Adenocarcinoma of colon † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Brain cancer metastatic † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Brain neoplasm † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Lung adenocarcinoma † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Lung adenocarcinoma stage III † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Lung cancer metastatic † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Metastases to thorax † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Squamous cell carcinoma of skin † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Nervous system disorders
Cerebrovascular accident † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	3/213 (1.41%)	4	1/212 (0.47%)	1	2/211 (0.95%)	2
Syncope † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	2/212 (0.94%)	2	2/211 (0.95%)	2
Transient ischaemic attack † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	2/213 (0.94%)	2	0/212 (0.00%)	0	1/211 (0.47%)	1
Altered state of consciousness † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Aphasia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Brain stem stroke † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Carotid artery stenosis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Cerebellar stroke † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Cerebral infarction † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	1/211 (0.47%)	1
Dementia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Ischaemic stroke † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Loss of consciousness † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Intracranial haematoma † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Intracranial mass † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Metabolic encephalopathy † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Seizure † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Psychiatric disorders
Panic attack † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	1/211 (0.47%)	1
Genitourinary symptom † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Haematuria † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Hydronephrosis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Urinary retention † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	1/211 (0.47%)	1
End stage renal disease † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Prostatomegaly † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Vaginal prolapse † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	2/213 (0.94%)	2	2/212 (0.94%)	2	2/211 (0.95%)	2
Dyspnoea † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	2/213 (0.94%)	2	1/212 (0.47%)	1	0/211 (0.00%)	0
Acute respiratory failure † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	1/212 (0.47%)	1	0/211 (0.00%)	0
Chronic obstructive pulmonary disease † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	1/212 (0.47%)	1	1/211 (0.47%)	1
Aspiration † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Hypoxia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Pleural effusion † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	2	0/212 (0.00%)	0	0/211 (0.00%)	0
Pneumonia aspiration † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	1/211 (0.47%)	1
Tachypnoea † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Atelectasis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Lung consolidation † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Pneumothorax † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Pulmonary artery thrombosis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Respiratory failure † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Skin and subcutaneous tissue disorders
Eczema † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	1/213 (0.47%)	1	0/212 (0.00%)	0	0/211 (0.00%)	0
Stasis dermatitis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Vascular disorders
Arteriosclerosis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Deep vein thrombosis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	1/211 (0.47%)	1
Hypertensive emergency † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	1/212 (0.47%)	1	0/211 (0.00%)	0
Aortic aneurysm † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Giant cell arteritis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Hypertension † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
Hypertensive urgency † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	1/211 (0.47%)	1
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pegcetacoplan Monthly: Ocular Study Eye		Pegcetacoplan EOM: Ocular Study Eye		Sham Pooled: Ocular Study Eye		Pegcetacoplan Monthly: Ocular Fellow Eye		Pegcetacoplan EOM: Ocular Fellow Eye		Sham Pooled: Ocular Fellow Eye		Pegcetacoplan Monthly: Non-ocular		Pegcetacoplan EOM: Non-ocular		Sham Pooled: Non-ocular
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	100/213 (46.95%)		95/212 (44.81%)		59/211 (27.96%)		69/213 (32.39%)		56/212 (26.42%)		65/211 (30.81%)		86/213 (40.38%)		72/212 (33.96%)		67/211 (31.75%)
Eye disorders
Conjunctival haemorrhage † 1	22/213 (10.33%)	39	19/212 (8.96%)	25	10/211 (4.74%)	10	2/213 (0.94%)	2	3/212 (1.42%)	3	3/211 (1.42%)	4	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Visual acuity reduced † 1	17/213 (7.98%)	21	20/212 (9.43%)	21	17/211 (8.06%)	28	13/213 (6.10%)	15	11/212 (5.19%)	13	19/211 (9.00%)	25	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Vitreous floaters † 1	17/213 (7.98%)	20	19/212 (8.96%)	25	2/211 (0.95%)	2	2/213 (0.94%)	3	5/212 (2.36%)	5	3/211 (1.42%)	3	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Neovascular age-related macular degeneration † 1	20/213 (9.39%)	21	14/212 (6.60%)	15	3/211 (1.42%)	3	9/213 (4.23%)	9	5/212 (2.36%)	5	11/211 (5.21%)	12	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Eye pain † 1	17/213 (7.98%)	19	16/212 (7.55%)	18	14/211 (6.64%)	18	4/213 (1.88%)	4	1/212 (0.47%)	1	2/211 (0.95%)	2	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Dry eye † 1	14/213 (6.57%)	15	14/212 (6.60%)	15	7/211 (3.32%)	7	13/213 (6.10%)	13	13/212 (6.13%)	14	5/211 (2.37%)	6	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Punctate keratitis † 1	16/213 (7.51%)	16	6/212 (2.83%)	6	0/211 (0.00%)	0	9/213 (4.23%)	9	4/212 (1.89%)	4	1/211 (0.47%)	1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Vitreous detachment † 1	7/213 (3.29%)	7	11/212 (5.19%)	12	8/211 (3.79%)	8	4/213 (1.88%)	4	3/212 (1.42%)	3	5/211 (2.37%)	5	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Blepharitis † 1	4/213 (1.88%)	4	11/212 (5.19%)	11	5/211 (2.37%)	6	3/213 (1.41%)	3	9/212 (4.25%)	10	4/211 (1.90%)	5	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Cataract † 1	8/213 (3.76%)	8	4/212 (1.89%)	5	11/211 (5.21%)	11	7/213 (3.29%)	7	6/212 (2.83%)	6	12/211 (5.69%)	12	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Low luminance best-corrected visual acuity decreased † 1	7/213 (3.29%)	7	5/212 (2.36%)	5	10/211 (4.74%)	11	10/213 (4.69%)	14	6/212 (2.83%)	7	11/211 (5.21%)	13	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Retinal haemorrhage † 1	9/213 (4.23%)	10	6/212 (2.83%)	7	4/211 (1.90%)	5	10/213 (4.69%)	15	5/212 (2.36%)	5	11/211 (5.21%)	13	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0
Infections and infestations
Urinary tract infection † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	23/213 (10.80%)	26	20/212 (9.43%)	22	22/211 (10.43%)	31
COVID-19 † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	15/213 (7.04%)	16	11/212 (5.19%)	11	10/211 (4.74%)	10
Nasopharyngitis † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	10/213 (4.69%)	11	5/212 (2.36%)	5	12/211 (5.69%)	14
Injury, poisoning and procedural complications
Fall † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	16/213 (7.51%)	17	16/212 (7.55%)	18	9/211 (4.27%)	10
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	15/213 (7.04%)	21	12/212 (5.66%)	15	7/211 (3.32%)	7
Nervous system disorders
Headache † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	12/213 (5.63%)	15	4/212 (1.89%)	4	9/211 (4.27%)	9
Vascular disorders
Hypertension † 1	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	0/213 (0.00%)	0	0/212 (0.00%)	0	0/211 (0.00%)	0	20/213 (9.39%)	20	16/212 (7.55%)	16	17/211 (8.06%)	17
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Apellis Clinical Trial Information Line
• Organization: Apellis Pharmaceuticals, Inc
• Phone: 1-833-284-6361
• EMail: clinicaltrials@apellis.com

• Responsible Party: Apellis Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03525613
• Other Study ID Numbers: APL2-304
• First Submitted: April 20, 2018
• First Posted: May 15, 2018
• Results First Submitted: May 15, 2023
• Results First Posted: July 6, 2023
• Last Update Posted: July 6, 2023