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

• Sponsor: Alcon Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02515942
• Collaborator: Novartis Institutes for BioMedical Research (Other)
• Enrollment: 114
• Arms: 3
• Actual Duration (Months): 26.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of 12 (every 28 days) intravitreal (IVT) injections of CLG561 as a monotherapy and in combination with LFG316 as compared to sham in subjects with geographic atrophy.

Condition or Disease	Intervention/Treatment	Phase
Geographic Atrophy	Drug: CLG561; Drug: LFG316; Drug: Sham injection	Phase 2

Detailed Description

This study consists of an up-to 30-day screening period, an approximately 336-day treatment period, and a follow-up period consisting of two visits occurring 4 and 16 weeks after the last administered injection.

Study Design

• Study Type: Interventional
• Actual Enrollment: 114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multi-Center, Single Masked, Sham Controlled, Proof-of-Concept Study of Intravitreal CLG561 as a Monotherapy and in Combination With LFG316 in Subjects With Geographic Atrophy
• Actual Study Start Date: Sep 25, 2015
• Actual Primary Completion Date: Aug 14, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CLG561 CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	Drug: CLG561
Experimental: CLG561+LFG316 CLG561 5mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	Drug: CLG561; Drug: LFG316
Sham Comparator: Sham Injection One sham injection every 28 days for total of 12 sham injections	Drug: Sham injection; Empty syringe (without a needle) placed against the eye

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug [Up to Day 421]

   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.

2. Mean Change From Baseline in Intraocular Pressure (IOP) [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]

   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.

3. Change in GA Lesion Size From Baseline to Day 337 as Measured by Fundus Autofluorescence (FAF) [Baseline (Day 1), Day 337]

   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.

Secondary Outcome Measures

1. Change in GA Lesion Size From Baseline to Day 85, 169, and 253 as Measured by FAF [Baseline (Day 1), Day 85, Day 169, Day 253]

   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.

2. Mean Change in GA Lesion Size From Baseline to Day 421 as Measured by FAF [Baseline (Day 1), Day 421]

   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. Day 421 measurements were only summarized descriptively and did not include any statistical modeling.

3. Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) [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]

   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.

4. Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS [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]

   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.

5. Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS [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]

   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.

6. Average Change in BCVA From Baseline to the Period Day 281 to Day 337 as Measured by ETDRS [Baseline (Day 1), Day 281, Day 309, Day 337]

   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.

7. Average Change in LLVA From Baseline to the Period Day 281 to Day 337 as Measured by ETDRS [Baseline (Day 1), Day 281, Day 309, Day 337]

   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.

8. Average LLVA Deficit (Letters) Change From Baseline at Day 281 to Day 337 as Measured by ETDRS [Baseline (Day 1), Day 281, Day 309, Day 337]

   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.

9. Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS [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]

   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.

10. Total CLG561 Serum Concentrations up to Day 421 [Baseline (Day 1), Day 2, Day 8, Day 15, Day 29, Day 85, Day 169, Day 253, Day 309, Day 337, Day 421]

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

11. Total LFG316 Serum Concentration up to Day 421 [Baseline (Day 1), Day 337, Day 421]

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

12. Percentage of Subjects With Anti-CLG561 Antibodies up to Day 421 [Baseline (Day 1), up to Day 421]

    Samples were collected and assessed for anti-CLG561 antibodies.

13. Percentage of Subjects With Anti-LFG316 Antibodies up to Day 421 [Baseline (Day 1), up to Day 421]

    Samples were collected and assessed for anti-LFG316 antibodies.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Sign written informed consent form;

• Geographic atrophy in both eyes;

• Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

• Pregnant or lactating women and women of child-bearing potential;

• Any medical condition (systemic or ophthalmic) that may preclude the safe administration of test article or safe participation in this study;

• Any contraindications or hypersensitivities to any component of the LFG316 or CLG561 solution;

• Any contraindications to IVT injections;

• Ocular surgery in either eye within 90 days of screening;

• Uncontrolled ocular hypertension or glaucoma in the study eye;

• Other protocol-specified exclusion criteria may apply.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Alcon Research
• Novartis Institutes for BioMedical Research

Investigators

• Study Director: Sr Clinical Manager, Pharma, GCRA, Alcon Research

Study Documents (Full-Text)

• Statistical Analysis Plan - Jan 8, 2018
• Study Protocol - Jan 20, 2016

More Information

Publications

None provided.

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT02515942
• Other Study ID Numbers: CLG561-2201; CCLG561X2201
• First Posted: Aug 5, 2015
• Last Update Posted: May 30, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Alcon Research: Geographic atrophy (GA); Macular degeneration; Dry age-related macular degeneration (AMD); Intravitreal (IVT); Retinal diseases; Fundus auto fluorescence (FAF)
• Additional relevant MeSH terms: Geographic Atrophy; Atrophy

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from 28 sites in the US and Puerto Rico.
Pre-assignment Detail	This reporting group includes all randomized participants.

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

Baseline Characteristics

Arm/Group Title	CLG561	CLG561+LFG316	Sham Injection	Total
Arm/Group Description	CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	One sham injection every 28 days for total of 12 sham injections	Total of all reporting groups
Overall Participants	36	39	39	114
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	77.7 (8.61)	78.8 (7.11)	78.7 (9.80)	78.4 (8.52)
Sex: Female, Male (Count of Participants)
Female	22 61.1%	21 53.8%	24 61.5%	67 58.8%
Male	14 38.9%	18 46.2%	15 38.5%	47 41.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 13.9%	3 7.7%	5 12.8%	13 11.4%
Not Hispanic or Latino	31 86.1%	35 89.7%	33 84.6%	99 86.8%
Unknown or Not Reported	0 0%	1 2.6%	1 2.6%	2 1.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	38 97.4%	38 33.3%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	35 97.2%	39 100%	0 0%	74 64.9%
More than one race	1 2.8%	0 0%	0 0%	1 0.9%
Unknown or Not Reported	0 0%	0 0%	1 2.6%	1 0.9%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug
Description	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.
Time Frame	Up to Day 421

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	CLG561	CLG561+LFG316	Sham Injection
Arm/Group Description	CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	One sham injection every 28 days for total of 12 sham injections
Measure Participants	36	39	39
Number [subjects]	0	0	0

2. Primary Outcome

Title	Mean Change From Baseline in Intraocular Pressure (IOP)
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

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

3. Primary Outcome

Title	Change in GA Lesion Size From Baseline to Day 337 as Measured by Fundus Autofluorescence (FAF)
Description	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.
Time Frame	Baseline (Day 1), Day 337

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CLG561	CLG561+LFG316	Sham Injection
Arm/Group Description	CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561 5 mg +LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	One sham injection every 28 days for total of 12 sham injections
Measure Participants	29	34	33
Least Squares Mean (80% Confidence Interval) [square millimeters (mm2)]	1.53	1.88	1.82

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from ANCOVA model with treatment, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal), baseline lesion size as covariates after multiple imputations.
Statistical Test of Hypothesis	p-Value	0.0636
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 80%; -0.64 to -0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Least squares mean for change from baseline from ANCOVA model with treatment, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal), baseline lesion size as covariates after multiple imputations.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1019
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 80%; -0.59 to 0.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Least squares mean for change from baseline from ANCOVA model with treatment, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal), baseline lesion size as covariates after multiple imputations.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5987
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 80%; -0.24 to 0.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change in GA Lesion Size From Baseline to Day 85, 169, and 253 as Measured by FAF
Description	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.
Time Frame	Baseline (Day 1), Day 85, Day 169, Day 253

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CLG561	CLG561+LFG316	Sham Injection
Arm/Group Description	CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	One sham injection every 28 days for total of 12 sham injections
Measure Participants	30	35	34
Change from BL at Day 85	0.41	0.41	0.37
Change from BL at Day 169	0.69	0.81	0.82
Change from BL at Day 253	1.08	1.33	1.25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 85
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5029
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 80%; -0.11 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 85
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.6820
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 80%; -0.07 to 0.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 85
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.6826
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 80%; -0.07 to 0.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 169
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.1545
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 80%; -0.28 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 169
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.1398
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 80%; -0.29 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 169
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4717
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 80%; -0.16 to 0.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 253
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0530
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 80%; -0.45 to -0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 253
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.1386
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 80%; -0.37 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 253
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.7087
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 80%; -0.11 to 0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Mean Change in GA Lesion Size From Baseline to Day 421 as Measured by FAF
Description	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. Day 421 measurements were only summarized descriptively and did not include any statistical modeling.
Time Frame	Baseline (Day 1), Day 421

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CLG561	CLG561+LFG316	Sham Injection
Arm/Group Description	CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561 5 mg +LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	One sham injection every 28 days for total of 12 sham injections
Measure Participants	30	35	34
Baseline (Day 1)	9.090 (3.9628)	9.070 (3.6955)	9.017 (4.2132)
Change from Baseline at Day 421	2.056 (1.0618)	2.449 (1.0691)	2.395 (1.1905)

6. Secondary Outcome

Title	Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS)
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CLG561	CLG561+LFG316	Sham Injection
Arm/Group Description	CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	One sham injection every 28 days for total of 12 sham injections
Measure Participants	35	37	38
Change from BL at Day 2	-0.93	1.79	-1.44
Change from BL at Day 8	2.14	2.46	0.86
Change from BL at Day 15	2.89	4.83	3.02
Change from BL at Day 29	3.28	5.29	1.25
Change from BL at Day 30	3.30	3.16	2.92
Change from BL at Day 57	3.65	4.69	4.25
Change from BL at Day 85	3.86	2.57	3.05
Change from BL at Day 113	3.09	3.60	3.40
Change from BL at Day 141	3.20	5.14	2.22
Change from BL at Day 169	2.62	3.57	3.61
Change from BL at Day 197	2.30	2.60	3.54
Change from BL at Day 225	2.98	3.33	1.87
Change from BL at Day 253	2.76	3.31	0.46
Change from BL at Day 281	1.52	2.08	0.67
Change from BL at Day 309	1.39	2.92	-0.75
Change from BL at Day 337	0.25	0.07	0.45

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 2
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.9243
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-2.72
	Confidence Interval	(2-Sided) 80%; -5.15 to -0.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 2
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3929
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 80%; -1.89 to 2.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 2
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0418
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	3.23
	Confidence Interval	(2-Sided) 80%; 0.85 to 5.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 8
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5632
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 80%; -2.91 to 2.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 8
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2575
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 80%; -1.25 to 3.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 8
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2058
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.61
	Confidence Interval	(2-Sided) 80%; -0.91 to 4.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 15
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.8392
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.94
	Confidence Interval	(2-Sided) 80%; -4.44 to 0.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 15
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5255
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effecgt
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 80%; -2.59 to 2.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 15
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.1685
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.81
	Confidence Interval	(2-Sided) 80%; -0.61 to 4.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 29
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.8544
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment
	Estimated Value	-2.01
	Confidence Interval	(2-Sided) 80%; -4.45 to 0.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 29
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.1402
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.03
	Confidence Interval	(2-Sided) 80%; -0.38 to 4.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 29
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0150
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	4.03
	Confidence Interval	(2-Sided) 80%; 1.67 to 6.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 30
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4682
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.14
	Confidence Interval	(2-Sided) 80%; -2.11 to 2.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 30
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4125
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 80%; -1.84 to 2.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 30
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4431
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.24
	Confidence Interval	(2-Sided) 80%; -1.94 to 2.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 57
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.6924
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.04
	Confidence Interval	(2-Sided) 80%; -3.72 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 57
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.6160
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.61
	Confidence Interval	(2-Sided) 80%; -3.26 to 2.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 57
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4149
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 80%; -2.18 to 3.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 85
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2582
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 80%; -1.27 to 3.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 85
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3402
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 80%; -1.72 to 3.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 85
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5976
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 80%; -2.99 to 2.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 113
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5916
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 80%; -3.30 to 2.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 113
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5564
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 80%; -3.05 to 2.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 113
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4625
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 80%; -2.53 to 2.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 141
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.8221
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.94
	Confidence Interval	(2-Sided) 80%; -4.64 to 0.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 141
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3179
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 80%; -1.68 to 3.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 141
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0773
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.92
	Confidence Interval	(2-Sided) 80%; 0.29 to 5.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 169
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.6708
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.95
	Confidence Interval	(2-Sided) 80%; -3.71 to 1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 169
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.6790
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.99
	Confidence Interval	(2-Sided) 80%; -3.71 to 1.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 169
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5070
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 80%; -2.72 to 2.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 197
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5487
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 80%; -3.44 to 2.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 197
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.6973
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.25
	Confidence Interval	(2-Sided) 80%; -4.35 to 1.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 197
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.6548
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.95
	Confidence Interval	(2-Sided) 80%; -4.00 to 2.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 225
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5533
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 80%; -3.76 to 3.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 225
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3358
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 80%; -2.25 to 4.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 225
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2850
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.46
	Confidence Interval	(2-Sided) 80%; -1.85 to 4.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 253
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5778
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.55
	Confidence Interval	(2-Sided) 80%; -4.14 to 3.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 253
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2018
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.30
	Confidence Interval	(2-Sided) 80%; -1.24 to 5.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 253
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.1457
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.85
	Confidence Interval	(2-Sided) 80%; -0.62 to 6.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 281
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5758
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.56
	Confidence Interval	(2-Sided) 80%; -4.29 to 3.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 281
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3833
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 80%; -2.84 to 4.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 281
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3083
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.41
	Confidence Interval	(2-Sided) 80%; -2.21 to 5.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 43

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 309
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.7063
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.54
	Confidence Interval	(2-Sided) 80%; -5.19 to 2.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 44

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 309
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2227
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.14
	Confidence Interval	(2-Sided) 80%; -1.46 to 5.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 45

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 309
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0907
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	3.68
	Confidence Interval	(2-Sided) 80%; 0.15 to 7.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 46

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 337
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4799
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 80%; -4.23 to 4.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 47

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 337
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5237
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 80%; -4.54 to 4.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 48

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 337
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5451
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 80%; -4.62 to 3.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CLG561	CLG561+LFG316	Sham Injection
Arm/Group Description	CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	One sham injection every 28 days for total of 12 sham injections
Measure Participants	35	37	38
Change from BL at Day 2	-0.57	-0.72	-1.03
Change from BL at Day 29	0.99	3.87	1.39
Change from BL at Day 57	2.41	1.89	1.18
Change from BL at Day 85	3.80	2.89	-0.15
Change from BL at Day 113	3.59	-0.09	1.67
Change from BL at Day 141	2.90	1.41	1.57
Change from BL at Day 169	1.40	3.03	2.78
Change from BL at Day 197	2.52	2.23	1.58
Change from BL at Day 225	2.47	0.69	0.75
Change from BL at Day 253	3.50	0.68	1.71
Change from BL at Day 281	3.21	1.90	0.79
Change from BL at Day 309	1.72	1.79	-0.61
Change from BL at Day 337	1.47	-1.09	-0.73

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 2
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4609
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.15
	Confidence Interval	(2-Sided) 80%; -1.79 to 2.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 2
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3771
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 80%; -1.44 to 2.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 2
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4161
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.32
	Confidence Interval	(2-Sided) 80%; -1.60 to 2.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 29
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.9385
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-2.88
	Confidence Interval	(2-Sided) 80%; -5.26 to -0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 29
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5862
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 80%; -2.76 to 1.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 29
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0875
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.48
	Confidence Interval	(2-Sided) 80%; 0.14 to 4.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 57
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4059
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.53
	Confidence Interval	(2-Sided) 80%; -2.32 to 3.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 57
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2860
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.24
	Confidence Interval	(2-Sided) 80%; -1.58 to 4.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 57
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3727
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 80%; -2.10 to 3.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 85
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3360
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 80%; -1.85 to 3.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 85
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0316
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	3.95
	Confidence Interval	(2-Sided) 80%; 1.24 to 6.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 85
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0762
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	3.04
	Confidence Interval	(2-Sided) 80%; 0.32 to 5.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 113
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0544
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	3.68
	Confidence Interval	(2-Sided) 80%; 0.75 to 6.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 113
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.1955
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.91
	Confidence Interval	(2-Sided) 80%; -0.95 to 4.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 113
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.7844
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.77
	Confidence Interval	(2-Sided) 80%; -4.65 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 141
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2973
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.49
	Confidence Interval	(2-Sided) 80%; -2.11 to 5.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 141
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3127
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 80%; -2.18 to 4.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 141
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5227
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 80%; -3.67 to 3.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 169
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.7643
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.63
	Confidence Interval	(2-Sided) 80%; -4.54 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 169
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.7331
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.38
	Confidence Interval	(2-Sided) 80%; -4.25 to 1.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 169
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4557
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.25
	Confidence Interval	(2-Sided) 80%; -2.59 to 3.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 197
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4549
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.29
	Confidence Interval	(2-Sided) 80%; -2.97 to 3.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 197
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3535
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 80%; -2.26 to 4.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 197
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3970
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 80%; -2.54 to 3.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 225
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2714
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.78
	Confidence Interval	(2-Sided) 80%; -1.99 to 5.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 225
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2741
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.72
	Confidence Interval	(2-Sided) 80%; -1.97 to 5.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 225
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5084
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 80%; -3.74 to 3.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 253
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.1537
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.82
	Confidence Interval	(2-Sided) 80%; -0.73 to 6.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 253
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2542
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.79
	Confidence Interval	(2-Sided) 80%; -1.69 to 5.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 253
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.6504
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.03
	Confidence Interval	(2-Sided) 80%; -4.46 to 2.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 281
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3405
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.30
	Confidence Interval	(2-Sided) 80%; -2.78 to 5.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 281
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2194
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.41
	Confidence Interval	(2-Sided) 80%; -1.59 to 6.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 281
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3596
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 80%; -2.87 to 5.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 309
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5086
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 80%; -4.04 to 3.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 309
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2211
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.33
	Confidence Interval	(2-Sided) 80%; -1.57 to 6.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 309
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2126
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.40
	Confidence Interval	(2-Sided) 80%; -1.47 to 6.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 337
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2053
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.56
	Confidence Interval	(2-Sided) 80%; -1.44 to 6.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 337
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2353
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.20
	Confidence Interval	(2-Sided) 80%; -1.72 to 6.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 337
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5471
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 80%; -4.24 to 3.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CLG561	CLG561+LFG316	Sham Injection
Arm/Group Description	CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	One sham injection every 28 days for total of 12 sham injections
Measure Participants	35	37	38
Change from BL at Day 2	-0.43	2.32	-0.15
Change from BL at Day 29	2.43	1.27	0.06
Change from BL at Day 57	1.38	2.54	3.07
Change from BL at Day 85	-0.10	-0.23	3.27
Change from BL at Day 113	-0.33	3.59	1.83
Change from BL at Day 141	0.45	4.30	0.83
Change from BL at Day 169	0.80	0.85	0.85
Change from BL at Day 197	-0.37	0.72	2.08
Change from BL at Day 225	-0.08	3.86	1.39
Change from BL at Day 253	-0.39	3.24	-0.85
Change from BL at Day 281	-2.13	1.09	0.14
Change from BL at Day 309	-0.62	2.02	0.07
Change from BL at Day 337	-1.35	2.55	1.37

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 2
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0913
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-2.74
	Confidence Interval	(2-Sided) 80%; -5.38 to -0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 2
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4454
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 80%; -2.89 to 2.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 2
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.8861
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.46
	Confidence Interval	(2-Sided) 80%; -0.16 to 5.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 29
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.7130
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 80%; -1.49 to 3.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 29
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.8759
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.37
	Confidence Interval	(2-Sided) 80%; -0.26 to 5.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 29
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.7256
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 80%; -1.39 to 3.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 57
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3111
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.17
	Confidence Interval	(2-Sided) 80%; -4.22 to 1.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 57
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2360
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.70
	Confidence Interval	(2-Sided) 80%; -4.73 to 1.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 57
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4110
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.53
	Confidence Interval	(2-Sided) 80%; -3.55 to 2.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 85
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5247
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.13
	Confidence Interval	(2-Sided) 80%; -2.57 to 2.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 85
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0534
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-3.37
	Confidence Interval	(2-Sided) 80%; -6.04 to -0.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 85
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0475
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-3.50
	Confidence Interval	(2-Sided) 80%; -6.18 to -0.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 113
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0575
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-3.92
	Confidence Interval	(2-Sided) 80%; -7.11 to -0.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 113
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.1876
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-2.16
	Confidence Interval	(2-Sided) 80%; -5.29 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 113
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.7644
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.76
	Confidence Interval	(2-Sided) 80%; -1.38 to 4.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 141
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0838
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-3.85
	Confidence Interval	(2-Sided) 80%; -7.42 to -0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 141
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4444
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 80%; -3.89 to 3.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 141
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.8977
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	3.47
	Confidence Interval	(2-Sided) 80%; -0.04 to 6.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 169
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4917
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 80%; -2.92 to 2.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 169
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4909
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 80%; -2.89 to 2.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 169
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4992
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 80%; -2.82 to 2.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 197
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.3285
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.09
	Confidence Interval	(2-Sided) 80%; -4.25 to 2.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 197
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.1568
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-2.45
	Confidence Interval	(2-Sided) 80%; -5.57 to 0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 197
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2867
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.36
	Confidence Interval	(2-Sided) 80%; -4.46 to 1.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 225
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0798
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-3.93
	Confidence Interval	(2-Sided) 80%; -7.51 to -0.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 225
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2962
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.47
	Confidence Interval	(2-Sided) 80%; -5.00 to 2.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 225
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.8163
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.46
	Confidence Interval	(2-Sided) 80%; -1.05 to 5.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 253
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.0708
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-3.64
	Confidence Interval	(2-Sided) 80%; -6.81 to -0.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 253
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.5750
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 80%; -2.67 to 3.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 253
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.9560
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	4.10
	Confidence Interval	(2-Sided) 80%; 1.03 to 7.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 281
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.1283
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-3.22
	Confidence Interval	(2-Sided) 80%; -6.86 to 0.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 281
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.2085
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-2.28
	Confidence Interval	(2-Sided) 80%; -5.88 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 281
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.6335
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 80%; -2.61 to 4.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 309
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.1778
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-2.64
	Confidence Interval	(2-Sided) 80%; -6.31 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 309
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.4027
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.70
	Confidence Interval	(2-Sided) 80%; -4.33 to 2.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 309
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.7570
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.94
	Confidence Interval	(2-Sided) 80%; -1.64 to 5.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	CLG561, CLG561+LFG316
	Comments	Change from baseline at Day 337
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.1132
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-3.90
	Confidence Interval	(2-Sided) 80%; -8.03 to 0.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	CLG561, Sham Injection
	Comments	Change from baseline at Day 337
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.1965
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-2.71
	Confidence Interval	(2-Sided) 80%; -6.80 to 1.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	CLG561+LFG316, Sham Injection
	Comments	Change from baseline at Day 337
	Type of Statistical Test	Superiority
	Comments	Least squares mean for change from baseline from repeated measures mixed effect model with treatment, visit and treatment*visit interaction, baseline lesion location (foveal vs. extrafoveal), baseline lesion type (unifocal vs. multifocal) and baseline value as fixed effects, and unstructured covariance for observations within the same subject.
Statistical Test of Hypothesis	p-Value	0.6471
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 80%; -2.85 to 5.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Average Change in BCVA From Baseline to the Period Day 281 to Day 337 as Measured by ETDRS
Description	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.
Time Frame	Baseline (Day 1), Day 281, Day 309, Day 337

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CLG561	CLG561+LFG316	Sham Injection
Arm/Group Description	CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	One sham injection every 28 days for total of 12 sham injections
Measure Participants	30	35	34
Mean (Standard Deviation) [letters]	3.0 (11.50)	2.3 (13.25)	-0.3 (11.23)

10. Secondary Outcome

Title	Average Change in LLVA From Baseline to the Period Day 281 to Day 337 as Measured by ETDRS
Description	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.
Time Frame	Baseline (Day 1), Day 281, Day 309, Day 337

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CLG561	CLG561+LFG316	Sham Injection
Arm/Group Description	CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	One sham injection every 28 days for total of 12 sham injections
Measure Participants	30	35	34
Mean (Standard Deviation) [letters]	3.6 (11.04)	0.4 (10.80)	-2.2 (17.01)

11. Secondary Outcome

Title	Average LLVA Deficit (Letters) Change From Baseline at Day 281 to Day 337 as Measured by ETDRS
Description	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.
Time Frame	Baseline (Day 1), Day 281, Day 309, Day 337

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CLG561	CLG561+LFG316	Sham Injection
Arm/Group Description	CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561 5 mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections	One sham injection every 28 days for total of 12 sham injections
Measure Participants	30	35	34
Mean (Standard Deviation) [letters]	-0.6 (8.91)	1.9 (12.96)	1.9 (16.82)

12. Secondary Outcome

Title	Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

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

13. Secondary Outcome

Title	Total CLG561 Serum Concentrations up to Day 421
Description	Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.
Time Frame	Baseline (Day 1), Day 2, Day 8, Day 15, Day 29, Day 85, Day 169, Day 253, Day 309, Day 337, Day 421

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CLG561	CLG561+LFG316
Arm/Group Description	CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561 5 mg +LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections
Measure Participants	36	39
Baseline	0 (0)	0 (0)
Day 2	998 (471)	475 (57)
Day 8	821 (483)	417 (90)
Day 15	476 (76)	428 (NA)
Day 29	181 (255)	0 (NA)
Day 85	271 (236)	0 (0)
Day 169	294 (225)	75 (160)
Day 253	97 (178)	36 (112)
Day 309	161 (236)	31 (113)
Day 337	281 (242)	54 (139)
Day 421	0 (0)	0 (0)

14. Secondary Outcome

Title	Total LFG316 Serum Concentration up to Day 421
Description	Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.
Time Frame	Baseline (Day 1), Day 337, Day 421

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CLG561+LFG316
Arm/Group Description	CLG561 5 mg +LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections
Measure Participants	39
Baseline	0 (NA)
Day 337	338 (NA)
Day 421	0 (0)

15. Secondary Outcome

Title	Percentage of Subjects With Anti-CLG561 Antibodies up to Day 421
Description	Samples were collected and assessed for anti-CLG561 antibodies.
Time Frame	Baseline (Day 1), up to Day 421

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	CLG561	CLG561+LFG316
Arm/Group Description	CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections	CLG561 5 mg +LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections
Measure Participants	36	39
Number [percentage of subjects]	0	7.7

16. Secondary Outcome

Title	Percentage of Subjects With Anti-LFG316 Antibodies up to Day 421
Description	Samples were collected and assessed for anti-LFG316 antibodies.
Time Frame	Baseline (Day 1), up to Day 421

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	CLG561+LFG316
Arm/Group Description	CLG561 5 mg +LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections
Measure Participants	39
Number [percentage of subjects]	0

Adverse Events

Time Frame	Day 1 through study completion, an average of 336 days
Adverse Event Reporting Description	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.
Arm/Group Title	CLG561		CLG561+LFG316		Sham Injection
Arm/Group Description	All subjects exposed to CLG561 10 mg		All subjects exposed to CLG561 5 mg + LFG316 5 mg		All subjects exposed to sham injection
All Cause Mortality
	CLG561		CLG561+LFG316		Sham Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/36 (2.8%)		0/39 (0%)		1/39 (2.6%)
Serious Adverse Events
	CLG561		CLG561+LFG316		Sham Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/36 (13.9%)		5/39 (12.8%)		7/39 (17.9%)
Cardiac disorders
Angina unstable	1/36 (2.8%)		0/39 (0%)		0/39 (0%)
Arteriosclerosis coronary artery	1/36 (2.8%)		0/39 (0%)		0/39 (0%)
Atrial fibrillation	1/36 (2.8%)		1/39 (2.6%)		0/39 (0%)
Myocardial infarction	0/36 (0%)		1/39 (2.6%)		1/39 (2.6%)
Eye disorders
Blindness	0/36 (0%)		1/39 (2.6%)		0/39 (0%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	0/36 (0%)		0/39 (0%)		1/39 (2.6%)
General disorders
Chest pain	0/36 (0%)		0/39 (0%)		1/39 (2.6%)
Infections and infestations
Clostridium difficile colitis	0/36 (0%)		0/39 (0%)		1/39 (2.6%)
Endophthalmitis	1/36 (2.8%)		0/39 (0%)		0/39 (0%)
Gastroenteritis	0/36 (0%)		0/39 (0%)		1/39 (2.6%)
Pneumonia	0/36 (0%)		2/39 (5.1%)		1/39 (2.6%)
Sepsis	0/36 (0%)		1/39 (2.6%)		0/39 (0%)
Injury, poisoning and procedural complications
Cataract traumatic	1/36 (2.8%)		0/39 (0%)		0/39 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma	1/36 (2.8%)		0/39 (0%)		0/39 (0%)
Ureteric cancer	0/36 (0%)		0/39 (0%)		1/39 (2.6%)
Nervous system disorders
Encephalopathy	1/36 (2.8%)		0/39 (0%)		0/39 (0%)
Spinal cord compression	0/36 (0%)		1/39 (2.6%)		0/39 (0%)
Transient ischaemic attack	1/36 (2.8%)		1/39 (2.6%)		1/39 (2.6%)
Psychiatric disorders
Mental status changes	0/36 (0%)		1/39 (2.6%)		0/39 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/36 (0%)		2/39 (5.1%)		0/39 (0%)
Pleural effusion	1/36 (2.8%)		0/39 (0%)		0/39 (0%)
Pulmonary oedema	1/36 (2.8%)		0/39 (0%)		0/39 (0%)
Other (Not Including Serious) Adverse Events
	CLG561		CLG561+LFG316		Sham Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/36 (75%)		31/39 (79.5%)		29/39 (74.4%)
Eye disorders
Anterior chamber cell	3/36 (8.3%)		1/39 (2.6%)		0/39 (0%)
Anterior chamber flare	2/36 (5.6%)		0/39 (0%)		0/39 (0%)
Blepharitis	1/36 (2.8%)		3/39 (7.7%)		5/39 (12.8%)
Cataract nuclear	0/36 (0%)		0/39 (0%)		2/39 (5.1%)
Conjunctival haemorrhage	7/36 (19.4%)		9/39 (23.1%)		5/39 (12.8%)
Conjunctival hyperaemia	4/36 (11.1%)		4/39 (10.3%)		0/39 (0%)
Conjunctivitis allergic	0/36 (0%)		0/39 (0%)		2/39 (5.1%)
Dry age-related macular degeneration	0/36 (0%)		2/39 (5.1%)		2/39 (5.1%)
Dry eye	3/36 (8.3%)		0/39 (0%)		2/39 (5.1%)
Eye irritation	2/36 (5.6%)		2/39 (5.1%)		4/39 (10.3%)
Eye pain	3/36 (8.3%)		5/39 (12.8%)		4/39 (10.3%)
Iridocyclitis	5/36 (13.9%)		0/39 (0%)		0/39 (0%)
Metamorphopsia	0/36 (0%)		2/39 (5.1%)		0/39 (0%)
Ocular discomfort	0/36 (0%)		0/39 (0%)		2/39 (5.1%)
Photophobia	0/36 (0%)		2/39 (5.1%)		0/39 (0%)
Posterior capsule opacification	1/36 (2.8%)		2/39 (5.1%)		1/39 (2.6%)
Punctate keratitis	2/36 (5.6%)		2/39 (5.1%)		0/39 (0%)
Retinal haemorrhage	3/36 (8.3%)		4/39 (10.3%)		1/39 (2.6%)
Uveitis	3/36 (8.3%)		0/39 (0%)		0/39 (0%)
Visual acuity reduced	12/36 (33.3%)		8/39 (20.5%)		5/39 (12.8%)
Vitreal cells	2/36 (5.6%)		1/39 (2.6%)		0/39 (0%)
Vitreous detachment	2/36 (5.6%)		2/39 (5.1%)		1/39 (2.6%)
Vitreous floaters	3/36 (8.3%)		9/39 (23.1%)		0/39 (0%)
Vitreous opacities	2/36 (5.6%)		0/39 (0%)		0/39 (0%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	0/36 (0%)		0/39 (0%)		2/39 (5.1%)
General disorders
Non-cardiac chest pain	2/36 (5.6%)		0/39 (0%)		0/39 (0%)
Oedema peripheral	3/36 (8.3%)		0/39 (0%)		1/39 (2.6%)
Immune system disorders
Seasonal allergy	2/36 (5.6%)		1/39 (2.6%)		1/39 (2.6%)
Infections and infestations
Bronchitis	3/36 (8.3%)		1/39 (2.6%)		2/39 (5.1%)
Gastroenteritis viral	0/36 (0%)		1/39 (2.6%)		2/39 (5.1%)
Influenza	0/36 (0%)		2/39 (5.1%)		2/39 (5.1%)
Nasopharyngitis	1/36 (2.8%)		3/39 (7.7%)		3/39 (7.7%)
Oral herpes	2/36 (5.6%)		0/39 (0%)		0/39 (0%)
Pneumonia	0/36 (0%)		2/39 (5.1%)		1/39 (2.6%)
Sinusitis	2/36 (5.6%)		4/39 (10.3%)		4/39 (10.3%)
Urinary tract infection	1/36 (2.8%)		2/39 (5.1%)		1/39 (2.6%)
Injury, poisoning and procedural complications
Contusion	0/36 (0%)		3/39 (7.7%)		1/39 (2.6%)
Fall	0/36 (0%)		1/39 (2.6%)		2/39 (5.1%)
Muscle strain	0/36 (0%)		0/39 (0%)		2/39 (5.1%)
Investigations
Blood creatine phosphokinase increased	0/36 (0%)		0/39 (0%)		2/39 (5.1%)
Blood triglycerides increased	0/36 (0%)		0/39 (0%)		2/39 (5.1%)
Intraocular pressure increased	4/36 (11.1%)		4/39 (10.3%)		0/39 (0%)
Prothrombin time prolonged	0/36 (0%)		0/39 (0%)		2/39 (5.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/36 (2.8%)		0/39 (0%)		2/39 (5.1%)
Arthritis	1/36 (2.8%)		1/39 (2.6%)		3/39 (7.7%)
Intervertebral disc degeneration	0/36 (0%)		2/39 (5.1%)		0/39 (0%)
Osteoarthritis	2/36 (5.6%)		0/39 (0%)		1/39 (2.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	0/36 (0%)		0/39 (0%)		2/39 (5.1%)
Nervous system disorders
Headache	0/36 (0%)		3/39 (7.7%)		1/39 (2.6%)
Sciatica	1/36 (2.8%)		0/39 (0%)		2/39 (5.1%)
Psychiatric disorders
Anxiety	0/36 (0%)		0/39 (0%)		2/39 (5.1%)
Renal and urinary disorders
Renal cyst	0/36 (0%)		2/39 (5.1%)		0/39 (0%)
Urinary incontinence	0/36 (0%)		0/39 (0%)		2/39 (5.1%)
Respiratory, thoracic and mediastinal disorders
Cough	2/36 (5.6%)		2/39 (5.1%)		3/39 (7.7%)
Epistaxis	1/36 (2.8%)		0/39 (0%)		3/39 (7.7%)
Wheezing	2/36 (5.6%)		0/39 (0%)		0/39 (0%)
Vascular disorders
Hypertension	4/36 (11.1%)		4/39 (10.3%)		5/39 (12.8%)
Hypotension	1/36 (2.8%)		2/39 (5.1%)		0/39 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Sponsor reserves the right of prior review of any publication or presentation of information related to the study.