Trial Outcomes & Findings for CLG561 Proof-of-Concept Study as a Monotherapy and in Combination With LFG316 in Subjects With Geographic Atrophy (GA) (NCT NCT02515942)

Last Updated: 2019-05-30

Results Overview

A serious adverse event (SAE) was defined as any adverse experience that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. All SAEs related to the study drug are reported. No statistical analysis was conducted.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

114 participants

Primary outcome timeframe

Up to Day 421

Results posted on

2019-05-30

Participant Flow

Subjects were recruited from 28 sites in the US and Puerto Rico.

This reporting group includes all randomized participants.

Participant milestones

Participant milestones
Measure	CLG561 CLG561 10 mg, one intravitreal (IVT) injection every 28 days for a total of 12 injections	CLG561+LFG316 CLG561 5 mg +LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection One sham injection every 28 days for total of 12 sham injections
Overall Study STARTED	36	39	39
Overall Study Safety Analysis Set	36	39	39
Overall Study Full Analysis Set (FAS)	35	37	38
Overall Study Per Protocol Analysis Set (PPS)	30	35	34
Overall Study Pharmacokinetics (PK) Analysis Set	36	39	0
Overall Study Completed Day 85	35	38	37
Overall Study Completed Day 169	32	37	37
Overall Study Completed Day 253	29	37	36
Overall Study Completed Day 337	30	36	35
Overall Study COMPLETED	29	36	35
Overall Study NOT COMPLETED	7	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	CLG561 CLG561 10 mg, one intravitreal (IVT) injection every 28 days for a total of 12 injections	CLG561+LFG316 CLG561 5 mg +LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection One sham injection every 28 days for total of 12 sham injections
Overall Study Adverse Event	5	0	0
Overall Study Death	0	0	1
Overall Study Lack of Efficacy	0	0	1
Overall Study Lost to Follow-up	2	0	0
Overall Study Withdrawal by Subject	0	3	2

Baseline Characteristics

CLG561 Proof-of-Concept Study as a Monotherapy and in Combination With LFG316 in Subjects With Geographic Atrophy (GA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CLG561 n=36 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=39 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection n=39 Participants One sham injection every 28 days for total of 12 sham injections	Total n=114 Participants Total of all reporting groups
Age, Continuous	77.7 years STANDARD_DEVIATION 8.61 • n=5 Participants	78.8 years STANDARD_DEVIATION 7.11 • n=7 Participants	78.7 years STANDARD_DEVIATION 9.80 • n=5 Participants	78.4 years STANDARD_DEVIATION 8.52 • n=4 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	21 Participants n=7 Participants	24 Participants n=5 Participants	67 Participants n=4 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	18 Participants n=7 Participants	15 Participants n=5 Participants	47 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants	35 Participants n=7 Participants	33 Participants n=5 Participants	99 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	38 Participants n=5 Participants	38 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	35 Participants n=5 Participants	39 Participants n=7 Participants	0 Participants n=5 Participants	74 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to Day 421

Population: Safety Analysis Set

Outcome measures

Outcome measures
Measure	CLG561 n=36 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=39 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection n=39 Participants One sham injection every 28 days for total of 12 sham injections
Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug	0 subjects	0 subjects	0 subjects

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 253, Day 281, Day 309

Population: Safety Analysis Set. At each time point, only subjects with a value at both baseline and that time point are included.

IOP (fluid pressure inside the eye) was measured by Goldmann applanation tonometry and reported in millimeters of mercury (mmHg). A higher IOP can be a greater risk for developing glaucoma or glaucoma progression (leading to optic nerve damage). Baseline is defined as the last measurement prior to first dose of treatment. A more negative change indicates a greater amount of improvement. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.

Outcome measures

Outcome measures
Measure	CLG561 n=36 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=39 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection n=39 Participants One sham injection every 28 days for total of 12 sham injections
Mean Change From Baseline in Intraocular Pressure (IOP) Change from BL at Day 169	0.4 mmHg Standard Deviation 4.35	-0.1 mmHg Standard Deviation 3.33	-0.6 mmHg Standard Deviation 3.75
Mean Change From Baseline in Intraocular Pressure (IOP) Change from BL at Day 197	-0.4 mmHg Standard Deviation 3.88	-0.0 mmHg Standard Deviation 3.74	-0.2 mmHg Standard Deviation 3.13
Mean Change From Baseline in Intraocular Pressure (IOP) Change from BL at Day 225	-0.3 mmHg Standard Deviation 3.72	-0.0 mmHg Standard Deviation 4.11	-0.4 mmHg Standard Deviation 3.40
Mean Change From Baseline in Intraocular Pressure (IOP) Change from BL at Day 253	0.6 mmHg Standard Deviation 4.39	-0.2 mmHg Standard Deviation 3.61	-1.1 mmHg Standard Deviation 3.75
Mean Change From Baseline in Intraocular Pressure (IOP) Change from BL at Day 281	1.6 mmHg Standard Deviation 8.32	0.5 mmHg Standard Deviation 3.72	-0.6 mmHg Standard Deviation 3.91
Mean Change From Baseline in Intraocular Pressure (IOP) Change from BL at Day 309	1.0 mmHg Standard Deviation 2.97	0.0 mmHg Standard Deviation 3.43	-1.2 mmHg Standard Deviation 4.00
Mean Change From Baseline in Intraocular Pressure (IOP) Baseline (BL) (Day 1)	15.1 mmHg Standard Deviation 3.58	14.5 mmHg Standard Deviation 3.42	15.5 mmHg Standard Deviation 3.54
Mean Change From Baseline in Intraocular Pressure (IOP) Change from BL at Day 29	-0.2 mmHg Standard Deviation 2.57	0.0 mmHg Standard Deviation 2.95	-0.7 mmHg Standard Deviation 3.74
Mean Change From Baseline in Intraocular Pressure (IOP) Change from BL at Day 57	-0.2 mmHg Standard Deviation 3.46	-0.4 mmHg Standard Deviation 2.70	-0.1 mmHg Standard Deviation 3.06
Mean Change From Baseline in Intraocular Pressure (IOP) Change from BL at Day 85	-0.1 mmHg Standard Deviation 2.80	-0.1 mmHg Standard Deviation 3.02	0.2 mmHg Standard Deviation 2.86
Mean Change From Baseline in Intraocular Pressure (IOP) Change from BL at Day 113	0.2 mmHg Standard Deviation 3.84	0.4 mmHg Standard Deviation 3.31	-0.7 mmHg Standard Deviation 2.69
Mean Change From Baseline in Intraocular Pressure (IOP) Change from BL at Day 141	0.4 mmHg Standard Deviation 2.93	0.1 mmHg Standard Deviation 3.82	-0.6 mmHg Standard Deviation 3.09

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 337

Population: PPS. Only subjects with a value at both baseline and that time point are included.

Geographic atrophy, also known as atrophic age-related macular degeneration (AMD) or advanced dry AMD, is an advanced form of age-related macular degeneration that can result in the progressive and irreversible loss of retina which can lead to a loss of visual function over time. Geographic atrophy (GA) lesion size was assessed by a Central Reading Center (CRC) using FAF. Baseline is defined as the last measurement prior to first dose of treatment. One eye (study eye) contributed to the analysis.

Outcome measures

Outcome measures
Measure	CLG561 n=29 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=34 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection n=33 Participants One sham injection every 28 days for total of 12 sham injections
Change in GA Lesion Size From Baseline to Day 337 as Measured by Fundus Autofluorescence (FAF)	1.53 square millimeters (mm2) Interval 1.31 to 1.74	1.88 square millimeters (mm2) Interval 1.68 to 2.08	1.82 square millimeters (mm2) Interval 1.61 to 2.03

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 85, Day 169, Day 253

Population: PPS. At each time point, only subjects with a value at both baseline and that time point are included.

Outcome measures

Outcome measures
Measure	CLG561 n=30 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=35 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection n=34 Participants One sham injection every 28 days for total of 12 sham injections
Change in GA Lesion Size From Baseline to Day 85, 169, and 253 as Measured by FAF Change from BL at Day 85	0.41 mm2 Interval 0.33 to 0.49	0.41 mm2 Interval 0.34 to 0.48	0.37 mm2 Interval 0.3 to 0.45
Change in GA Lesion Size From Baseline to Day 85, 169, and 253 as Measured by FAF Change from BL at Day 169	0.69 mm2 Interval 0.58 to 0.8	0.81 mm2 Interval 0.71 to 0.92	0.82 mm2 Interval 0.72 to 0.93
Change in GA Lesion Size From Baseline to Day 85, 169, and 253 as Measured by FAF Change from BL at Day 253	1.08 mm2 Interval 0.93 to 1.22	1.33 mm2 Interval 1.2 to 1.46	1.25 mm2 Interval 1.11 to 1.38

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 421

Population: PPS. At each time point, only subjects with a value at both baseline and that time point are included.

Outcome measures

Outcome measures
Measure	CLG561 n=30 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=35 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection n=34 Participants One sham injection every 28 days for total of 12 sham injections
Mean Change in GA Lesion Size From Baseline to Day 421 as Measured by FAF Baseline (Day 1)	9.090 mm2 Standard Deviation 3.9628	9.070 mm2 Standard Deviation 3.6955	9.017 mm2 Standard Deviation 4.2132
Mean Change in GA Lesion Size From Baseline to Day 421 as Measured by FAF Change from Baseline at Day 421	2.056 mm2 Standard Deviation 1.0618	2.449 mm2 Standard Deviation 1.0691	2.395 mm2 Standard Deviation 1.1905

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 2, Day 8, Day 15, Day 29, Day 30, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 253, Day 281, Day 309, Day 337

Population: FAS. At each time point, only subjects with a value at both baseline and that time point are included.

BCVA was assessed using ETDRS testing at 4 meters. Baseline is defined as the last measurement prior to first dose of treatment. BCVA change was defined as a change in letters read from the baseline assessment. A positive change value indicates improvement. One eye (study eye) contributed to the analysis.

Outcome measures

Outcome measures
Measure	CLG561 n=35 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=37 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection n=38 Participants One sham injection every 28 days for total of 12 sham injections
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 337	0.25 letters Interval -2.92 to 3.42	0.07 letters Interval -2.93 to 3.08	0.45 letters Interval -2.52 to 3.41
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 2	-0.93 letters Interval -2.65 to 0.78	1.79 letters Interval 0.09 to 3.48	-1.44 letters Interval -3.1 to 0.22
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 8	2.14 letters Interval 0.31 to 3.98	2.46 letters Interval 0.67 to 4.26	0.86 letters Interval -0.88 to 2.6
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 15	2.89 letters Interval 1.1 to 4.69	4.83 letters Interval 3.1 to 6.55	3.02 letters Interval 1.33 to 4.7
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 29	3.28 letters Interval 1.53 to 5.02	5.29 letters Interval 3.61 to 6.96	1.25 letters Interval -0.4 to 2.9
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 30	3.30 letters Interval 1.7 to 4.91	3.16 letters Interval 1.62 to 4.71	2.92 letters Interval 1.4 to 4.44
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 57	3.65 letters Interval 1.74 to 5.55	4.69 letters Interval 2.84 to 6.54	4.25 letters Interval 2.42 to 6.08
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 85	3.86 letters Interval 2.05 to 5.68	2.57 letters Interval 0.8 to 4.35	3.05 letters Interval 1.31 to 4.8
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 113	3.09 letters Interval 1.11 to 5.07	3.60 letters Interval 1.65 to 5.54	3.40 letters Interval 1.5 to 5.29
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 141	3.20 letters Interval 1.28 to 5.12	5.14 letters Interval 3.27 to 7.01	2.22 letters Interval 0.39 to 4.05
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 169	2.62 letters Interval 0.64 to 4.6	3.57 letters Interval 1.67 to 5.47	3.61 letters Interval 1.73 to 5.48
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 197	2.30 letters Interval 0.05 to 4.54	2.60 letters Interval 0.42 to 4.77	3.54 letters Interval 1.41 to 5.67
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 225	2.98 letters Interval 0.54 to 5.41	3.33 letters Interval 0.98 to 5.68	1.87 letters Interval -0.43 to 4.17
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 253	2.76 letters Interval 0.18 to 5.34	3.31 letters Interval 0.85 to 5.77	0.46 letters Interval -1.96 to 2.88
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 281	1.52 letters Interval -1.17 to 4.21	2.08 letters Interval -0.48 to 4.63	0.67 letters Interval -1.86 to 3.2
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Change from BL at Day 309	1.39 letters Interval -1.24 to 4.01	2.92 letters Interval 0.43 to 5.42	-0.75 letters Interval -3.22 to 1.71

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 2, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 253, Day 281, Day 309, Day 337

Population: FAS. At each time point, only subjects with a value at both baseline and that time point are included.

Low Luminance Visual Acuity (VA) was assessed using ETDRS testing at 4 meters with a neutral density filter to reduce chart luminance to 3 candelas/m2. Baseline is defined as the last measurement prior to first dose of treatment. BCVA change was defined as a change in letters read from the baseline assessment. A positive change value indicates improvement. One eye (study eye) contributed to the analysis.

Outcome measures

Outcome measures
Measure	CLG561 n=35 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=37 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection n=38 Participants One sham injection every 28 days for total of 12 sham injections
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 253	3.50 letters Interval 0.95 to 6.04	0.68 letters Interval -1.76 to 3.12	1.71 letters Interval -0.67 to 4.08
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 2	-0.57 letters Interval -1.93 to 0.79	-0.72 letters Interval -2.09 to 0.65	-1.03 letters Interval -2.36 to 0.29
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 29	0.99 letters Interval -0.71 to 2.69	3.87 letters Interval 2.21 to 5.53	1.39 letters Interval -0.23 to 3.02
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 57	2.41 letters Interval 0.4 to 4.43	1.89 letters Interval -0.11 to 3.88	1.18 letters Interval -0.78 to 3.13
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 85	3.80 letters Interval 1.86 to 5.75	2.89 letters Interval 0.96 to 4.83	-0.15 letters Interval -2.03 to 1.73
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 113	3.59 letters Interval 1.52 to 5.65	-0.09 letters Interval -2.16 to 1.98	1.67 letters Interval -0.31 to 3.65
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 141	2.90 letters Interval 0.36 to 5.44	1.41 letters Interval -1.1 to 3.93	1.57 letters Interval -0.85 to 3.99
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 169	1.40 letters Interval -0.68 to 3.47	3.03 letters Interval 1.01 to 5.05	2.78 letters Interval 0.81 to 4.75
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 197	2.52 letters Interval 0.2 to 4.83	2.23 letters Interval -0.05 to 4.5	1.58 letters Interval -0.62 to 3.78
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 225	2.47 letters Interval -0.2 to 5.14	0.69 letters Interval -1.94 to 3.32	0.75 letters Interval -1.79 to 3.29
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 281	3.21 letters Interval 0.3 to 6.12	1.90 letters Interval -0.93 to 4.73	0.79 letters Interval -1.96 to 3.55
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 309	1.72 letters Interval -1.12 to 4.56	1.79 letters Interval -0.96 to 4.53	-0.61 letters Interval -3.29 to 2.06
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 337	1.47 letters Interval -1.38 to 4.32	-1.09 letters Interval -3.85 to 1.68	-0.73 letters Interval -3.42 to 1.96

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 2, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 253, Day 281, Day 309, Day 337

Population: FAS. At each time point, only subjects with a value at both baseline and that time point are included.

Low Luminance Visual Acuity (VA) was assessed using ETDRS testing at 4 meters with a neutral density filter to reduce chart luminance to 3 candelas/m2. A deficit in LLVA is defined as a loss in letters read from baseline. Baseline is defined as the last measurement prior to first dose of treatment. A negative change value indicates improvement (more letters read). One eye (study eye) contributed to the analysis.

Outcome measures

Outcome measures
Measure	CLG561 n=35 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=37 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection n=38 Participants One sham injection every 28 days for total of 12 sham injections
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 141	0.45 letters Interval -2.08 to 2.99	4.30 letters Interval 1.79 to 6.81	0.83 letters Interval -1.58 to 3.25
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 169	0.80 letters Interval -1.25 to 2.86	0.85 letters Interval -1.15 to 2.85	0.85 letters Interval -1.1 to 2.81
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 29	2.43 letters Interval 0.54 to 4.32	1.27 letters Interval -0.57 to 3.12	0.06 letters Interval -1.76 to 1.88
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 197	-0.37 letters Interval -2.62 to 1.88	0.72 letters Interval -1.49 to 2.93	2.08 letters Interval -0.07 to 4.23
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 2	-0.43 letters Interval -2.28 to 1.43	2.32 letters Interval 0.45 to 4.18	-0.15 letters Interval -1.96 to 1.67
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 57	1.38 letters Interval -0.79 to 3.55	2.54 letters Interval 0.4 to 4.69	3.07 letters Interval 0.97 to 5.18
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 85	-0.10 letters Interval -2.01 to 1.81	-0.23 letters Interval -2.14 to 1.68	3.27 letters Interval 1.41 to 5.13
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 113	-0.33 letters Interval -2.58 to 1.92	3.59 letters Interval 1.34 to 5.85	1.83 letters Interval -0.34 to 3.99
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 225	-0.08 letters Interval -2.63 to 2.47	3.86 letters Interval 1.35 to 6.36	1.39 letters Interval -1.04 to 3.82
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 253	-0.39 letters Interval -2.68 to 1.89	3.24 letters Interval 1.06 to 5.42	-0.85 letters Interval -2.99 to 1.28
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 281	-2.13 letters Interval -4.75 to 0.49	1.09 letters Interval -1.43 to 3.6	0.14 letters Interval -2.33 to 2.61
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 309	-0.62 letters Interval -3.26 to 2.01	2.02 letters Interval -0.53 to 4.56	0.07 letters Interval -2.42 to 2.57
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 337	-1.35 letters Interval -4.32 to 1.62	2.55 letters Interval -0.32 to 5.41	1.37 letters Interval -1.43 to 4.16

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 281, Day 309, Day 337

Population: PPS. At each time point, only subjects with a value at both baseline and that time point are included.

BCVA was assessed using ETDRS testing at 4 meters. Day 281, Day 309, and Day 337 were averaged and compared to baseline. BCVA change was defined as a change in letters read from the baseline assessment. A positive change value indicates improvement. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.

Outcome measures

Outcome measures
Measure	CLG561 n=30 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=35 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection n=34 Participants One sham injection every 28 days for total of 12 sham injections
Average Change in BCVA From Baseline to the Period Day 281 to Day 337 as Measured by ETDRS	3.0 letters Standard Deviation 11.50	2.3 letters Standard Deviation 13.25	-0.3 letters Standard Deviation 11.23

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 281, Day 309, Day 337

Population: PPS. At each time point, only subjects with a value at both baseline and that time point are included.

LLVA was assessed at 4 meters using a neutral density filter to reduce chart luminance to 3 candelas/m2. Baseline is defined as the last measurement prior to first dose of treatment. Day 281, Day 309, and Day 337 were averaged and compared to baseline. BCVA change was defined as a change in letters read from the baseline assessment. A positive change value indicates improvement. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.

Outcome measures

Outcome measures
Measure	CLG561 n=30 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=35 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection n=34 Participants One sham injection every 28 days for total of 12 sham injections
Average Change in LLVA From Baseline to the Period Day 281 to Day 337 as Measured by ETDRS	3.6 letters Standard Deviation 11.04	0.4 letters Standard Deviation 10.80	-2.2 letters Standard Deviation 17.01

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 281, Day 309, Day 337

Population: PPS. At each time point, only subjects with a value at both baseline and that time point are included.

LLVA was assessed at 4 meters using a neutral density filter to reduce chart luminance to 3 candelas/m2. A deficit in LLVA is defined as a loss in letters read from baseline. Baseline is defined as the last measurement prior to first dose of treatment. Day 281, Day 309, and Day 337 were averaged and compared to baseline. A negative change value indicates improvement (more letters read). One eye (study eye) contributed to the analysis.

Outcome measures

Outcome measures
Measure	CLG561 n=30 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=35 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection n=34 Participants One sham injection every 28 days for total of 12 sham injections
Average LLVA Deficit (Letters) Change From Baseline at Day 281 to Day 337 as Measured by ETDRS	-0.6 letters Standard Deviation 8.91	1.9 letters Standard Deviation 12.96	1.9 letters Standard Deviation 16.82

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 2, Day 8, Day 15, Day 29, Day 30, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 253, Day 281, Day 309, Day 337

Population: FAS. At each time point, only subjects with a value at both baseline and that time point are included.

BCVA was assessed using ETDRS testing at 4 meters. Baseline is defined as the last measurement prior to first dose of treatment. BCVA change was defined as a change in letters read from the baseline assessment and is reported categorically. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.

Outcome measures

Outcome measures
Measure	CLG561 n=35 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=37 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection n=38 Participants One sham injection every 28 days for total of 12 sham injections
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 2, ≥ 15 letters	2.9 percentage of subjects	2.8 percentage of subjects	0.0 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 2, ≥ 5 letters	20.0 percentage of subjects	27.8 percentage of subjects	10.8 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 8, ≤ -10 letters	5.9 percentage of subjects	5.6 percentage of subjects	5.3 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 8, ≤ -15 letters	0.0 percentage of subjects	2.8 percentage of subjects	0.0 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 29, ≥ 10 letters	20.6 percentage of subjects	18.9 percentage of subjects	10.5 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 30, ≤ -5 letters	6.1 percentage of subjects	11.1 percentage of subjects	13.5 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 57, ≤ -5 letters	8.6 percentage of subjects	13.5 percentage of subjects	13.5 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 85, ≥ 15 letters	8.6 percentage of subjects	5.6 percentage of subjects	8.1 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 113, ≥ 10 letters	22.9 percentage of subjects	22.9 percentage of subjects	13.2 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 253, ≤ -15 letters	3.4 percentage of subjects	8.3 percentage of subjects	11.1 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 281, ≥ 5 letters	43.3 percentage of subjects	44.4 percentage of subjects	28.6 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 281, ≤ -5 letters	26.7 percentage of subjects	25.0 percentage of subjects	25.7 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 2, ≥ 10 letters	8.6 percentage of subjects	5.6 percentage of subjects	2.7 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 2, ≤ -5 letters	20.0 percentage of subjects	5.6 percentage of subjects	18.9 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 2, ≤ -10 letters	5.7 percentage of subjects	2.8 percentage of subjects	5.4 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 2, ≤ -15 letters	5.7 percentage of subjects	0.0 percentage of subjects	5.4 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 8, ≥ 15 letters	2.9 percentage of subjects	5.6 percentage of subjects	0.0 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 8, ≥ 10 letters	23.5 percentage of subjects	5.6 percentage of subjects	5.3 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 8, ≥ 5 letters	29.4 percentage of subjects	27.8 percentage of subjects	21.1 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 8, ≤ -5 letters	8.8 percentage of subjects	8.3 percentage of subjects	13.2 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 15, ≥ 15 letters	12.1 percentage of subjects	5.6 percentage of subjects	7.9 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 15, ≥ 10 letters	18.2 percentage of subjects	11.1 percentage of subjects	15.8 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 15, ≥ 5 letters	36.4 percentage of subjects	36.1 percentage of subjects	26.3 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 15, ≤ -5 letters	6.1 percentage of subjects	8.3 percentage of subjects	15.8 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 15, ≤ -10 letters	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 15, ≤ -15 letters	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 29, ≥ 15 letters	5.9 percentage of subjects	8.1 percentage of subjects	2.6 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 29, ≥ 5 letters	41.2 percentage of subjects	37.8 percentage of subjects	18.4 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 29, ≤ -5 letters	11.8 percentage of subjects	5.4 percentage of subjects	13.2 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 29, ≤ -10 letters	5.9 percentage of subjects	2.7 percentage of subjects	5.3 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 29, ≤ -15 letters	0.0 percentage of subjects	0.0 percentage of subjects	2.6 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 30, ≥ 15 letters	12.1 percentage of subjects	5.6 percentage of subjects	8.1 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 30, ≥ 10 letters	18.2 percentage of subjects	13.9 percentage of subjects	13.5 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 30, ≥ 5 letters	45.5 percentage of subjects	33.3 percentage of subjects	24.3 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 30, ≤ -10 letters	0.0 percentage of subjects	2.8 percentage of subjects	5.4 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 30, ≤ -15 letters	0.0 percentage of subjects	2.8 percentage of subjects	2.7 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 57, ≥ 15 letters	11.4 percentage of subjects	5.4 percentage of subjects	10.8 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 57, ≥ 10 letters	22.9 percentage of subjects	16.2 percentage of subjects	16.2 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 57, ≥ 5 letters	48.6 percentage of subjects	45.9 percentage of subjects	35.1 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 57, ≤ -10 letters	2.9 percentage of subjects	2.7 percentage of subjects	2.7 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 57, ≤ -15 letters	0.00 percentage of subjects	0.00 percentage of subjects	0.00 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 85, ≥ 10 letters	28.6 percentage of subjects	13.9 percentage of subjects	13.5 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 85, ≥ 5 letters	45.7 percentage of subjects	38.9 percentage of subjects	24.3 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 85, ≤ -5 letters	8.6 percentage of subjects	16.7 percentage of subjects	13.5 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 85, ≤ -10 letters	0.0 percentage of subjects	5.6 percentage of subjects	2.7 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 85, ≤ -15 letters	0.0 percentage of subjects	2.8 percentage of subjects	0.0 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 113, ≥ 15 letters	8.6 percentage of subjects	2.9 percentage of subjects	7.9 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 113, ≥ 5 letters	40.0 percentage of subjects	40.0 percentage of subjects	23.7 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 113, ≤ -5 letters	5.7 percentage of subjects	17.1 percentage of subjects	13.2 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 113, ≤ -10 letters	2.9 percentage of subjects	8.6 percentage of subjects	5.3 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 113, ≤ -15 letters	0.0 percentage of subjects	0.0 percentage of subjects	2.6 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 141, ≥ 15 letters	14.7 percentage of subjects	5.6 percentage of subjects	10.5 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 141, ≥ 10 letters	23.5 percentage of subjects	19.4 percentage of subjects	15.8 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 141, ≥ 5 letters	44.1 percentage of subjects	41.7 percentage of subjects	23.7 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 141 ≤ -5 letters	8.8 percentage of subjects	2.8 percentage of subjects	26.3 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 141, ≤ -10 letters	5.9 percentage of subjects	0.0 percentage of subjects	7.9 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 141, ≤ -15 letters	2.9 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 169, ≥ 15 letters	12.5 percentage of subjects	2.7 percentage of subjects	13.5 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 169, ≥ 10 letters	21.9 percentage of subjects	13.5 percentage of subjects	18.9 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 169, ≥ 5 letters	37.5 percentage of subjects	35.1 percentage of subjects	24.3 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 169, ≤ -5 letters	21.9 percentage of subjects	18.9 percentage of subjects	10.8 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 169, ≤ -10 letters	3.1 percentage of subjects	5.4 percentage of subjects	2.7 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 169, ≤ -15 letters	0.0 percentage of subjects	2.7 percentage of subjects	0.0 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 197, ≥ 15 letters	15.2 percentage of subjects	2.8 percentage of subjects	10.8 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 197, ≥ 10 letters	30.3 percentage of subjects	13.9 percentage of subjects	18.9 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 197, ≥ 5 letters	45.5 percentage of subjects	41.7 percentage of subjects	32.4 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 197, ≤ -5 letters	21.2 percentage of subjects	19.4 percentage of subjects	16.2 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 197, ≤ -10 letters	9.1 percentage of subjects	11.1 percentage of subjects	10.8 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 197, ≤ -15 letters	6.1 percentage of subjects	2.8 percentage of subjects	5.4 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 225, ≥ 15 letters	21.9 percentage of subjects	8.6 percentage of subjects	8.1 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 225, ≥ 10 letters	28.1 percentage of subjects	20.0 percentage of subjects	10.8 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 225, ≥ 5 letters	37.5 percentage of subjects	45.7 percentage of subjects	21.6 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 225, ≤ -5 letters	21.9 percentage of subjects	20.0 percentage of subjects	24.3 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 225, ≤ -10 letters	9.4 percentage of subjects	5.7 percentage of subjects	16.2 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 225, ≤ -15 letters	6.3 percentage of subjects	5.7 percentage of subjects	2.7 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 253, ≥ 15 letters	17.2 percentage of subjects	5.6 percentage of subjects	13.9 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 253, ≥ 10 letters	34.5 percentage of subjects	30.6 percentage of subjects	16.7 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 253, ≥ 5 letters	44.8 percentage of subjects	38.9 percentage of subjects	16.7 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 253, ≤ -5 letters	24.1 percentage of subjects	19.4 percentage of subjects	27.8 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 253, ≤ -10 letters	3.4 percentage of subjects	13.9 percentage of subjects	19.4 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 281, ≥ 15 letters	23.3 percentage of subjects	8.3 percentage of subjects	8.6 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 281, ≥ 10 letters	33.3 percentage of subjects	22.2 percentage of subjects	14.3 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 281, ≤ -10 letters	6.7 percentage of subjects	22.2 percentage of subjects	20.0 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 281, ≤ -15 letters	6.7 percentage of subjects	11.1 percentage of subjects	11.4 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 309, ≥ 15 letters	20.0 percentage of subjects	8.6 percentage of subjects	2.9 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 309, ≥ 10 letters	23.3 percentage of subjects	22.9 percentage of subjects	11.4 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 309, ≥ 5 letters	43.3 percentage of subjects	40.7 percentage of subjects	25.7 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 309, ≤ -5 letters	20.0 percentage of subjects	22.9 percentage of subjects	31.4 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 309, ≤ -10 letters	10.0 percentage of subjects	8.6 percentage of subjects	22.9 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 309, ≤ -15 letters	3.3 percentage of subjects	5.7 percentage of subjects	8.6 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 337, ≥ 15 letters	16.7 percentage of subjects	8.6 percentage of subjects	5.7 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 337, ≥ 10 letters	30.0 percentage of subjects	20.0 percentage of subjects	11.4 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 337, ≥ 5 letters	43.3 percentage of subjects	40.0 percentage of subjects	25.7 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 337, ≤ -5 letters	26.7 percentage of subjects	22.9 percentage of subjects	34.3 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 337, ≤ -10 letters	13.3 percentage of subjects	14.3 percentage of subjects	14.3 percentage of subjects
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS Change from BL at Day 337, ≤ -15 letters	6.7 percentage of subjects	11.4 percentage of subjects	5.7 percentage of subjects

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 2, Day 8, Day 15, Day 29, Day 85, Day 169, Day 253, Day 309, Day 337, Day 421

Population: PK Analysis Set. At each time point, only subjects with a value at both baseline and that time point are included.

Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.

Outcome measures

Outcome measures
Measure	CLG561 n=36 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=39 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection One sham injection every 28 days for total of 12 sham injections
Total CLG561 Serum Concentrations up to Day 421 Baseline	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0	—
Total CLG561 Serum Concentrations up to Day 421 Day 2	998 ng/mL Standard Deviation 471	475 ng/mL Standard Deviation 57	—
Total CLG561 Serum Concentrations up to Day 421 Day 8	821 ng/mL Standard Deviation 483	417 ng/mL Standard Deviation 90	—
Total CLG561 Serum Concentrations up to Day 421 Day 15	476 ng/mL Standard Deviation 76	428 ng/mL Standard Deviation NA Standard deviation was not estimated due to low number of subjects with events.	—
Total CLG561 Serum Concentrations up to Day 421 Day 29	181 ng/mL Standard Deviation 255	0 ng/mL Standard Deviation NA Standard deviation was not estimated due to low number of subjects with events.	—
Total CLG561 Serum Concentrations up to Day 421 Day 85	271 ng/mL Standard Deviation 236	0 ng/mL Standard Deviation 0	—
Total CLG561 Serum Concentrations up to Day 421 Day 169	294 ng/mL Standard Deviation 225	75 ng/mL Standard Deviation 160	—
Total CLG561 Serum Concentrations up to Day 421 Day 253	97 ng/mL Standard Deviation 178	36 ng/mL Standard Deviation 112	—
Total CLG561 Serum Concentrations up to Day 421 Day 309	161 ng/mL Standard Deviation 236	31 ng/mL Standard Deviation 113	—
Total CLG561 Serum Concentrations up to Day 421 Day 337	281 ng/mL Standard Deviation 242	54 ng/mL Standard Deviation 139	—
Total CLG561 Serum Concentrations up to Day 421 Day 421	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0	—

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 337, Day 421

Population: PK Analysis Set. At each time point, only subjects with a value at both baseline and that time point are included.

Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.

Outcome measures

Outcome measures
Measure	CLG561 n=39 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection One sham injection every 28 days for total of 12 sham injections
Total LFG316 Serum Concentration up to Day 421 Baseline	0 ng/mL Standard Deviation NA Standard deviation was not estimated due to low number of subjects with events.	—	—
Total LFG316 Serum Concentration up to Day 421 Day 337	338 ng/mL Standard Deviation NA Standard deviation was not estimated due to low number of subjects with events.	—	—
Total LFG316 Serum Concentration up to Day 421 Day 421	0 ng/mL Standard Deviation 0	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1), up to Day 421

Population: IG analysis set: All subjects in the safety analysis set with evaluable immunogenicity (IG) data and with no major protocol deviations that had an impact on the assessment of immunogenicity.

Samples were collected and assessed for anti-CLG561 antibodies.

Outcome measures

Outcome measures
Measure	CLG561 n=36 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 n=39 Participants CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection One sham injection every 28 days for total of 12 sham injections
Percentage of Subjects With Anti-CLG561 Antibodies up to Day 421	0 percentage of subjects	7.7 percentage of subjects	—

SECONDARY outcome

Timeframe: Baseline (Day 1), up to Day 421

Samples were collected and assessed for anti-LFG316 antibodies.

Outcome measures

Outcome measures
Measure	CLG561 n=39 Participants CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561+LFG316 CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Sham Injection One sham injection every 28 days for total of 12 sham injections
Percentage of Subjects With Anti-LFG316 Antibodies up to Day 421	0 percentage of subjects	—	—

Adverse Events

CLG561

Serious events: 5 serious events

Other events: 27 other events

Deaths: 1 deaths

CLG561+LFG316

Serious events: 5 serious events

Other events: 31 other events

Deaths: 0 deaths

Sham Injection

Serious events: 7 serious events

Other events: 29 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

WW Brand Medical Director Ophtha, GMA Ophthalmics

Alcon, A Novartis Division

Phone: 1-888-451-3937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
Publication restrictions are in place

Restriction type: OTHER

Measure	CLG561 n=36 participants at risk All subjects exposed to CLG561 10 mg	CLG561+LFG316 n=39 participants at risk All subjects exposed to CLG561 5 mg + LFG316 5 mg	Sham Injection n=39 participants at risk All subjects exposed to sham injection
Cardiac disorders Angina unstable	2.8% 1/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Cardiac disorders Arteriosclerosis coronary artery	2.8% 1/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Cardiac disorders Atrial fibrillation	2.8% 1/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Cardiac disorders Myocardial infarction	0.00% 0/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Eye disorders Blindness	0.00% 0/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
General disorders Chest pain	0.00% 0/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Infections and infestations Clostridium difficile colitis	0.00% 0/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Infections and infestations Endophthalmitis	2.8% 1/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Infections and infestations Gastroenteritis	0.00% 0/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Infections and infestations Pneumonia	0.00% 0/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	5.1% 2/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Infections and infestations Sepsis	0.00% 0/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Injury, poisoning and procedural complications Cataract traumatic	2.8% 1/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	2.8% 1/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ureteric cancer	0.00% 0/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Nervous system disorders Encephalopathy	2.8% 1/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Nervous system disorders Spinal cord compression	0.00% 0/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Nervous system disorders Transient ischaemic attack	2.8% 1/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Psychiatric disorders Mental status changes	0.00% 0/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	2.6% 1/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	5.1% 2/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.8% 1/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	2.8% 1/36 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.	0.00% 0/39 • Day 1 through study completion, an average of 336 days Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Safety Analysis Set.