A Study Investigating the Efficacy and Safety of Lampalizumab Intravitreal Injections in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (CHROMA)

• ClinicalTrials.gov Identifier: NCT02247479
• Recruitment Status: Terminated
• First Posted: September 25, 2014
• Results First Posted: April 23, 2019
• Last Update Posted: June 26, 2019
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Geographic Atrophy
• Interventions: Drug: Lampalizumab; Other: Sham
• Enrollment: 906

Participant Flow

Recruitment Details	A total of 906 participants were randomized to the study from 131 investigation sites across 19 countries. The study was terminated early by the Sponsor due to lack of efficacy.
Pre-assignment Details	This study enrolled participants with bilateral Geographic Atrophy (GA) secondary to Age-Related Macular Degeneration (AMD) and no signs of prior or active choroidal neovascularization (CNV), age >= 50 years with a valid complement factor I (CFI)-profile biomarker result.

Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Period Title: Overall Study
Started	305	298	303
Completed	163	160	165
Not Completed	142	138	138
Reason Not Completed
Adverse Event	8	9	8
Death	5	4	6
Lost to Follow-up	3	3	1
Non-compliance	0	0	1
Withdrawal by Subject	25	29	24
Study Terminated by Sponsor	98	88	94
Physician Decision	1	0	2
Unspecified Reason	2	5	2

Baseline Characteristics

Arm/Group Title		Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W	Total
Arm/Group Description		Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.	Total of all reporting groups
Overall Number of Baseline Participants		305	298	303	906
Baseline Analysis Population Description		Intent-to-treat (ITT) population included all the participants who were randomized to the study.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	305 participants	298 participants	303 participants	906 participants
		78.5 (7.8)	77.5 (7.9)	78.3 (8.5)	78.1 (8.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	305 participants	298 participants	303 participants	906 participants
	Female	186 61.0%	182 61.1%	185 61.1%	553 61.0%
	Male	119 39.0%	116 38.9%	118 38.9%	353 39.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	305 participants	298 participants	303 participants	906 participants
	American Indian or Alaska Native	0 0.0%	1 0.3%	1 0.3%	2 0.2%
	Native Hawaiian or other Pacific Islander	0 0.0%	1 0.3%	0 0.0%	1 0.1%
	White	302 99.0%	294 98.7%	295 97.4%	891 98.3%
	Multiple	0 0.0%	0 0.0%	1 0.3%	1 0.1%
	Unknown	3 1.0%	2 0.7%	6 2.0%	11 1.2%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	305 participants	298 participants	303 participants	906 participants
	Hispanic or Latino	20 6.6%	17 5.7%	18 5.9%	55 6.1%
	Not Hispanic or Latino	279 91.5%	278 93.3%	282 93.1%	839 92.6%
	Not Stated	2 0.7%	3 1.0%	1 0.3%	6 0.7%
	Unknown	4 1.3%	0 0.0%	2 0.7%	6 0.7%
Geographic Atrophy (GA) Area, as Assessed by Fundus Autofluoresence (FAF) [1] [2]; Mean (Standard Deviation); Unit of measure: Millimeter square (mm^2)
	Number Analyzed	305 participants	298 participants	302 participants	905 participants
		7.953 (3.925)	7.910 (3.887)	8.116 (4.236)	7.993 (4.016)
		[1] Measure Description: At baseline the area of GA was assessed by FAF.; [2] Measure Analysis Population Description: ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.
Number of Absolute Scotomatous Points as Assessed by Mesopic Micrometry [1] [2]; Mean (Standard Deviation); Unit of measure: Absolute scotomatous points
	Number Analyzed	44 participants	33 participants	39 participants	116 participants
		29.1 (16.8)	25.2 (13.4)	20.5 (13.4)	25.1 (15.1)
		[1] Measure Description: Scotomatous points were the testing points on microperimetry examination that were centered on the macula and reported a lack of retinal sensitivity within the range tested, a maximum of 68 points were tested within this range. Higher results indicate expansion of absolute scotoma and higher number of abolute scotomatous points. Mesopic microperimetry assessments were performed post-dilation on the study eye only, and the data was forwarded to the central reading center.; [2] Measure Analysis Population Description: The microperimetry analysis population consisted of all participants who met the microperimetry eligibility criteria assessed by the reading center (participants at selected sites only; participants grouped according to treatment assigned at randomization).
Macular Sensitivity as Assessed by Mesopic Microperimetry [1] [2]; Mean (Standard Deviation); Unit of measure: Decibel (dB)
	Number Analyzed	44 participants	33 participants	39 participants	116 participants
		5.40 (3.37)	6.37 (4.02)	7.38 (3.40)	6.34 (3.64)
		[1] Measure Description: Mesopic microperimetry was used to assess macular sensitivity and assessments were performed post-dilation on the study eye only, and the data was forwarded to the central reading center.; [2] Measure Analysis Population Description: The microperimetry analysis population consisted of all participants who met the microperimetry eligibility criteria assessed by the reading center (participants at selected sites only; participants grouped according to treatment assigned at randomization).
Best Corrected Visual Acuity (BCVA) Score as Assessed by Early Treatment Diabetic Retinopathy Study [1] [2]; Mean (Standard Deviation); Unit of measure: Letters
	Number Analyzed	301 participants	295 participants	301 participants	897 participants
		65.9 (9.9)	66.1 (10.0)	66.4 (10.1)	66.2 (10.0)
		[1] Measure Description: BCVA score was based on the number of letters read correctly on the ETDRS visual acuity chart assessed at a starting distance of 4 meters. BCVA score testing was performed prior to dilating the eyes. BCVA score ranges from 0 to 100 letters in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity).; [2] Measure Analysis Population Description: ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.
Low Luminance Visual Acuity (LLVA) as Assessed by ETDRS Chart Under Low Luminance Conditions [1] [2]; Mean (Standard Deviation); Unit of measure: Letters
	Number Analyzed	299 participants	287 participants	293 participants	879 participants
		36.0 (15.7)	36.9 (17.8)	36.2 (16.7)	36.4 (16.7)
		[1] Measure Description: The LLVA was measured by placing a 2.0-log-unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart. The assessment was performed prior to dilating the eyes. LLVA score ranges from 0 to 100 letters in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity).; [2] Measure Analysis Population Description: ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.
Binocular Reading Speed as Assessed by Minnesota Low-Vision Reading Test or Radner Reading Charts [1] [2]; Mean (Standard Deviation); Unit of measure: Words per minute (wpm)
	Number Analyzed	278 participants	262 participants	269 participants	809 participants
		106.89 (57.98)	109.18 (60.14)	104.22 (62.37)	106.74 (60.12)
		[1] Measure Description: Minnesota Low-Vision Reading (MNRead) acuity cards were continuous-text reading-acuity cards suitable for measuring reading acuity and reading speed of normal and low-vision participants. A stopwatch was used to record time to a tenth of a second. Sentences that could not be read or were not attempted due to vision should be recorded as 0 for time and 10 for errors. Radner Reading Cards were suitable for measuring reading speed, reading visual acuity, and critical print size. Reading test was stopped when reading time was longer than 20 seconds or when participant was making severe errors.; [2] Measure Analysis Population Description: ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.
National Eye Institute Visual Functioning Questionnaire 25-item (NEI VFQ-25) Version Composite Score [1] [2]; Mean (Standard Deviation); Unit of measure: Score on a scale
	Number Analyzed	276 participants	275 participants	282 participants	833 participants
		66.16 (17.33)	64.80 (16.12)	65.19 (17.27)	65.38 (16.91)
		[1] Measure Description: NEI-VFQ-25 questionnaire included 25 items based on which overall composite VFQ score and 12 subscales were derived: near activities, distance activities, general health,general vision, ocular pain, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision and peripheral vision. Response to each question converted to 0-100 score. Each subscale, total score=average of items contributing to score. For each subscale and total score, score range: 0 to 100, a higher score represents better functioning.; [2] Measure Analysis Population Description: ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.
Mean Functional Reading Independence (FRI) Index [1] [2]; Mean (Standard Deviation); Unit of measure: Score on a scale
	Number Analyzed	276 participants	273 participants	280 participants	829 participants
		2.69 (0.83)	2.71 (0.79)	2.70 (0.82)	2.70 (0.81)
		[1] Measure Description: The FRI was an interviewer-administered questionnaire with 7-items on functional reading activities most relevant to GA AMD participants. It has one total index score. For each FRI Index reading activity performed in the past 7 days, participants were asked about the extent to which they required vision aids, adjustments in the activity, or help from another participant. Mean FRI Index scores range from 1 to 4, with higher scores indicating greater independence.; [2] Measure Analysis Population Description: ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.
NEI VFQ-25 Near Activity Subscale Score [1] [2]; Mean (Standard Deviation); Unit of measure: Score on a scale
	Number Analyzed	276 participants	275 participants	282 participants	833 participants
		54.98 (20.98)	53.78 (20.56)	53.67 (22.21)	54.14 (21.25)
		[1] Measure Description: NEI-VFQ-25 questionnaire included 25 items based on near activities, which are defined as reading ordinary print in newspapers, performing work or hobbies requiring near vision, or finding something on a crowded shelf. Response to each question converted to 0-100 score. Subscale=average of items contributing to score. For this subscale the score range is 0 to 100, a higher score represents better functioning.; [2] Measure Analysis Population Description: ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.
NEI VFQ-25 Distance Activity Subscale Score [1] [2]; Mean (Standard Deviation); Unit of measure: Score on a scale
	Number Analyzed	276 participants	275 participants	282 participants	833 participants
		62.86 (21.46)	60.97 (20.48)	62.10 (22.16)	61.98 (21.37)
		[1] Measure Description: NEI-VFQ-25 questionnaire included 25 items based on which distance activities was measured. Distance activities are defined as reading street signs or names on stores, and going down stairs, steps, or curbs. Response to each question converted to 0-100 score. Subscale=average of items contributing to score. For this subscale the score range is 0 to 100, a higher score represents better functioning.; [2] Measure Analysis Population Description: ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.
Monocular Maximum Reading Speed as Assessed by MNRead Charts or Radner Reading Charts [1] [2]; Mean (Standard Deviation); Unit of measure: Wpm
	Number Analyzed	278 participants	265 participants	271 participants	814 participants
		80.89 (52.95)	85.18 (54.55)	79.49 (54.23)	81.82 (53.89)
		[1] Measure Description: MNRead acuity cards were continuous-text reading-acuity cards suitable for measuring the reading acuity and reading speed of normal and low-vision participants. A stopwatch was used to record time to a tenth of a second. Sentences that could not be read or were not attempted due to vision should be recorded as 0 for time and 10 for errors. Radner Reading Cards were suitable for measuring reading speed, reading visual acuity, and critical print size. Reading test was stopped when reading time was longer than 20 seconds or when participant was making severe errors.; [2] Measure Analysis Population Description: ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.
GA Area in Complement Factor I (CFI) Positive Participants [1] [2]; Mean (Standard Deviation); Unit of measure: Mm^2
	Number Analyzed	181 participants	176 participants	177 participants	534 participants
		8.015 (3.915)	8.152 (4.118)	8.406 (4.399)	8.190 (4.142)
		[1] Measure Description: For CFI profile, positive biomarker status refers to the presence (carrier) of the risk allele at CFI and at least one risk allele at complement factor H (CFH) or risk locus containing both complement component 2 and complement factor B (C2/CFB).; [2] Measure Analysis Population Description: ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.
GA Area in CFI Negative Participants [1] [2]; Mean (Standard Deviation); Unit of measure: Mm^2
	Number Analyzed	124 participants	122 participants	125 participants	371 participants
		7.864 (3.952)	7.560 (3.515)	7.705 (3.975)	7.710 (3.814)
		[1] Measure Description: For CFI profile, negative biomarker status refers to the absence of the risk allele at CFI and at least one risk allele at CFH or C2/CFB.; [2] Measure Analysis Population Description: ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Geographic Atrophy (GA) Area, as Assessed by Fundus Autofluoresence (FAF) at Week 48
Description	The change in GA lesion area was measured by FAF and analysis of FAF images was performed by the central reading center. A positive change from baseline indicates an increase in size of GA lesion area (worsening; disease progression).
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all the participants who were randomized to the study. Participants analyzed in this outcome measure were those included in Mixed-effect model repeated measures (MMRM) analysis.

Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description:	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Number of Participants Analyzed	274	259	270
Mean (Standard Error); Unit of Measure: millimeter square (mm^2)
	2.035 (0.066)	2.016 (0.068)	2.086 (0.067)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q4W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, visit, treatment-by-visit interaction, baseline GA area, lesion location, contiguity, biomarker status, modified baseline BCVA and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8381
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-0.019
	Confidence Interval	(2-Sided) 95%; -0.206 to 0.167
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, visit, treatment-by-visit interaction, baseline GA area, lesion location, contiguity, biomarker status, modified baseline BCVA and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5901
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	0.051
	Confidence Interval	(2-Sided) 95%; -0.134 to 0.236
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Change From Baseline in GA Area in Complement Factor I (CFI) Positive and Negative Participants at Week 48
Description	For CFI profile, positive or negative biomarker status refers to the presence (carrier) or absence of the risk allele at CFI and at least one risk allele at complement factor H (CFH) or risk locus containing both complement component 2 and complement factor B (C2/CFB).The change in GA lesion area was measured by FAF and analysis of FAF images was performed by the central reading center. A positive change from baseline indicates an increase in size of GA lesion area (worsening; disease progression).
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all the participants who were randomized to the study. The analysis was done specifically for CFI-positive and negative participants. Number analyzed for each row signifies the participants evaluated for specified categories for each reporting group.

Arm/Group Title		Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description:		Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Number of Participants Analyzed		305	298	303
Mean (Standard Error); Unit of Measure: mm^2
CFI-Positive Participants	Number Analyzed	162 participants	152 participants	160 participants
		2.067 (0.086)	2.045 (0.089)	2.144 (0.087)
CFI-Negative Participants	Number Analyzed	112 participants	107 participants	110 participants
		2.006 (0.103)	1.974 (0.105)	2.012 (0.104)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q4W
	Comments	CFI Positive: MMRM analysis uses change as response variable and included treatment group, visit, treatment-by-visit interaction, baseline GA area, lesion location, contiguity, biomarker status, modified baseline BCVA and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8612
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-0.022
	Confidence Interval	(2-Sided) 95%; -0.266 to 0.223
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	CFI Positive: MMRM analysis uses change as response variable and included treatment group, visit, treatment-by-visit interaction, baseline GA area, lesion location, contiguity, biomarker status, modified baseline BCVA and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5317
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	0.077
	Confidence Interval	(2-Sided) 95%; -0.165 to 0.319
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q4W
	Comments	CFI Negative: MMRM analysis uses change as response variable and included treatment group, visit, treatment-by-visit interaction, baseline GA area, lesion location, contiguity, biomarker status, modified baseline BCVA and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8240
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-0.033
	Confidence Interval	(2-Sided) 95%; -0.322 to 0.257
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	CFI Negative: MMRM analysis uses change as response variable and included treatment group, visit, treatment-by-visit interaction, baseline GA area, lesion location, contiguity, biomarker status, modified baseline BCVA and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9676
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	0.006
	Confidence Interval	(2-Sided) 95%; -0.283 to 0.294
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Change From Baseline in Number of Absolute Scotomatous Points as Assessed by Mesopic Micrometry at Week 48
Description	Scotomatous points were the testing points on microperimetry examination that were centered on the macula and reported a lack of retinal sensitivity within the range tested, a maximum of 68 points were tested within this range. Higher results indicate expansion of absolute scotoma and higher number of abolute scotomatous points. Mesopic microperimetry assessments were performed post-dilation on the study eye only, and the data was forwarded to the central reading center. The data was collected up to Week 48 instead of Week 96, due to early termination of the study. A positive change from baseline indicates an increase in the number of absolute scotomatous points (more lack of retinal sensitivity); disease worsening.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

The microperimetry analysis population consisted of all participants who met the microperimetry eligibility criteria assessed by the reading center (participants at selected sites only; participants grouped according to treatment assigned at randomization). Participants analyzed in this outcome measure were those included in MMRM analysis.

Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description:	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Number of Participants Analyzed	30	26	26
Mean (Standard Error); Unit of Measure: absolute scotomatous points
	8.3 (1.7)	8.1 (1.8)	8.3 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q4W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, visit, treatment-by-visit interaction, baseline number of absolute scotomatous points, GA lesion location, contiguity, biomarker status, modified baseline BCVA and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9350
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -5.2 to 4.8
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, visit, treatment-by-visit interaction, baseline number of absolute scotomatous points, GA lesion location, contiguity, biomarker status, modified baseline BCVA and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9789
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -5.0 to 5.2
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Change From Baseline in Mean Macular Sensitivity as Assessed by Mesopic Microperimetry at Week 48
Description	Mesopic microperimetry was used to assess macular sensitivity and assessments were performed post-dilation on the study eye only, and the data was forwarded to the central reading center. A negative change from baseline indicates a decrease in the mean macular sensitivity; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

The microperimetry analysis population consisted of all participants who met the microperimetry eligibility criteria assessed by the reading center (participants at selected sites only; participants grouped according to treatment assigned at randomization). Participants analyzed in this outcome measure were those included in MMRM analysis.

Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description:	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Number of Participants Analyzed	30	26	26
Mean (Standard Error); Unit of Measure: decibel (dB)
	-1.61 (0.33)	-1.33 (0.34)	-2.24 (0.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q4W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, visit, treatment-by-visit interaction, baseline mean macular sensitivity, GA lesion location, contiguity, biomarker status, modified baseline BCVA and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5538
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 95%; -0.66 to 1.22
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, visit, treatment-by-visit interaction, baseline mean macular sensitivity, GA lesion location, contiguity, biomarker status, modified baseline BCVA and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2032
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-0.63
	Confidence Interval	(2-Sided) 95%; -1.60 to 0.35
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Change From Baseline in Best Corrected Visual Acuity (BCVA) Score as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart at Week 48
Description	BCVA score was based on the number of letters read correctly on the ETDRS visual acuity chart assessed at a starting distance of 4 meters (m). BCVA score testing was performed prior to dilating the eyes. BCVA score ranges from 0 to 100 letters in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). A negative change from baseline indicates a decrease in the visual acuity; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all the participants who were randomized to the study. Participants analyzed in this outcome measure were those included in MMRM analysis.

Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description:	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Number of Participants Analyzed	267	259	261
Mean (Standard Error); Unit of Measure: letters
	-4.5 (0.6)	-3.4 (0.6)	-4.6 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q4W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, visit, treatment-by-visit interaction, baseline BCVA, GA lesion location, biomarker status, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2547
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -0.7 to 2.8
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, visit, treatment-by-visit interaction, baseline BCVA, GA lesion location, biomarker status, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8423
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.9 to 1.6
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Percentage of Participants With Less Than 15 Letters Loss From Baseline in BCVA Score at Week 48
Description	Loss of less than 15 letters from baseline was assessed by the ETDRS chart at a starting distance of 4 meters (m). BCVA was measured using an eye chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The data was collected up to Week 48 instead of Week 96, due to early termination of the study.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.

Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description:	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Number of Participants Analyzed	267	259	262
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	85.8; (81.6 to 90.0)	88.8; (85.0 to 92.6)	87.0; (83.0 to 91.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q4W
	Comments	Week 48: The adjusted analysis was based on a logistic regression analysis. The model included terms for treatment group, baseline BCVA, baseline GA lesion location, biomarker status, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3248
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; 0.8 to 2.2
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	Week 48: The adjusted analysis was based on a logistic regression analysis. The model included terms for treatment group, baseline BCVA, baseline GA lesion location, biomarker status, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7209
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; 0.7 to 1.8
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Change From Baseline in Low Luminance Visual Acuity (LLVA) as Assessed by ETDRS Chart Under Low Luminance Conditions at Week 48
Description	The LLVA was measured by placing a 2.0-log-unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart. The assessment was performed prior to dilating the eyes. LLVA score ranges from 0 to 100 letters in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The data was collected up to Week 48 instead of Week 96, due to early termination of the study.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all the participants who were randomized to the study. Participants analyzed in this outcome measure were those included in MMRM analysis.

Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description:	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Number of Participants Analyzed	265	251	252
Mean (Standard Error); Unit of Measure: letters
	-3.0 (0.7)	-2.4 (0.7)	-2.7 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q4W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, visit, treatment-by-visit interaction, baseline LLVA, GA lesion location, biomarker status, modified baseline BCVA ETDRS chart Snellen equivalent category, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5695
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -1.4 to 2.6
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, visit, treatment-by-visit interaction, baseline LLVA, GA lesion location, biomarker status, modified baseline BCVA ETDRS chart Snellen equivalent category, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7865
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -1.7 to 2.3
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Percentage of Participants With Less Than 15 Letters Loss From Baseline in LLVA Score at Week 48
Description	Loss of less than 15 letters from baseline was assessed by the ETDRS chart at a starting distance of 4 m. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.

Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description:	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Number of Participants Analyzed	265	251	253
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	86.8; (82.7 to 90.9)	85.3; (80.9 to 89.6)	86.6; (82.4 to 90.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q4W
	Comments	Week 48: The adjusted analysis was based on a logistic regression analysis. The model included terms for treatment group, baseline LLVA, baseline GA lesion location, biomarker status, modified baseline BCVA ETDRS chart Snellen equivalent category, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9448
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; 0.6 to 1.7
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	Week 48: The adjusted analysis was based on a logistic regression analysis. The model included terms for treatment group, baseline LLVA, baseline GA lesion location, biomarker status, modified baseline BCVA ETDRS chart Snellen equivalent category, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8764
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; 0.6 to 1.8
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Change From Baseline in Binocular Reading Speed as Assessed by Minnesota Low-Vision Reading Test (MNRead) Charts or Radner Reading Charts at Week 48
Description	MNRead acuity cards were continuous-text reading-acuity cards suitable for measuring the reading acuity and reading speed of normal and low-vision participants. The MNRead acuity cards consisted of single, simple sentences with equal numbers of characters. A stopwatch was used to record time to a tenth of a second. Sentences that could not be read or were not attempted due to vision should be recorded as 0 for time and 10 for errors. The Radner Reading Cards were suitable for measuring reading speed, reading visual acuity, and critical print size. The reading test was stopped when the reading time was longer than 20 seconds or when the participant was making severe errors. A negative change from baseline indicates a decrease in the binocular reading speed; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all the participants who were randomized to the study. Participants analyzed in this outcome measure were those included in MMRM analysis.

Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description:	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Number of Participants Analyzed	242	223	229
Mean (Standard Error); Unit of Measure: words per minute (wpm)
	-18.97 (2.37)	-13.32 (2.47)	-19.96 (2.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q4W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, baseline maximum reading speed, type of reading charts, baseline BCVA of better seeing eye, biomarker status, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0991
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	5.66
	Confidence Interval	(2-Sided) 95%; -1.07 to 12.38
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, baseline maximum reading speed, type of reading charts, baseline BCVA of better seeing eye, biomarker status, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7713
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-0.99
	Confidence Interval	(2-Sided) 95%; -7.66 to 5.69
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Change From Baseline in Monocular Maximum Reading Speed as Assessed by MNRead Charts or Radner Reading Charts at Week 48
Description	MNRead acuity cards were continuous-text reading-acuity cards suitable for measuring the reading acuity and reading speed of normal and low-vision participants. The MNRead acuity cards consisted of single, simple sentences with equal numbers of characters. A stopwatch was used to record time to a tenth of a second. Sentences that could not be read or were not attempted due to vision should be recorded as 0 for time and 10 for errors. The Radner Reading Cards were suitable for measuring reading speed, reading visual acuity, and critical print size. The reading test was stopped when the reading time was longer than 20 seconds or when the participant was making severe errors. A negative change from baseline indicates a decrease in the monocular reading speed; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all the participants who were randomized to the study. Participants analyzed in this outcome measure were those included in MMRM analysis.

Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description:	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Number of Participants Analyzed	243	229	233
Mean (Standard Error); Unit of Measure: wpm
	-19.63 (2.41)	-17.91 (2.49)	-18.16 (2.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q4W
	Comments	MMRM analysis uses change as response variable included terms for treatment group, baseline maximum reading speed, type of reading charts, biomarker status, modified baseline BCVA and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6204
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	1.72
	Confidence Interval	(2-Sided) 95%; -5.09 to 8.53
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	MMRM analysis uses change as response variable included terms for treatment group, baseline maximum reading speed, type of reading charts, biomarker status, modified baseline BCVA and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6705
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	1.47
	Confidence Interval	(2-Sided) 95%; -5.31 to 8.25
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Change From Baseline in National Eye Institute Visual Functioning Questionnaire 25-item (NEI VFQ-25) Version Composite Score at Week 48
Description	NEI-VFQ-25 questionnaire included 25 items based on which overall composite VFQ score and 12 subscales were derived: near activities, distance activities, general health,general vision, ocular pain, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision and peripheral vision. Response to each question converted to 0-100 score. Each subscale, total score=average of items contributing to score. For each subscale and total score, score range: 0 to 100, a higher score represents better functioning. A negative change from baseline indicates a decrease in the visual functioning; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all the participants who were randomized to the study. Participants analyzed in this outcome measure were those included in MMRM analysis.

Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description:	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Number of Participants Analyzed	239	234	248
Mean (Standard Error); Unit of Measure: scores on a scale
	-1.31 (0.71)	-1.66 (0.72)	-2.87 (0.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, baseline score, baseline BCVA of better seeing eye, biomarker status, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7246
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -2.35 to 1.64
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, baseline score, baseline BCVA of better seeing eye, biomarker status, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1193
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-1.56
	Confidence Interval	(2-Sided) 95%; -3.53 to 0.40
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Change From Baseline in NEI VFQ-25 Near Activity Subscale Score at Week 48
Description	NEI-VFQ-25 questionnaire included 25 items based on which near activities were measured. Near activities are defined as reading ordinary print in newspapers, performing work or hobbies requiring near vision, or finding something on a crowded shelf. Response to each question converted to 0-100 score. Subscale=average of items contributing to score. For this subscale the score range is 0 to 100, a higher score represents better functioning. A negative change from baseline indicates a decrease in the near visual activities; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all the participants who were randomized to the study. Participants analyzed in this outcome measure were those included in MMRM analysis.

Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description:	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Number of Participants Analyzed	239	234	248
Mean (Standard Error); Unit of Measure: score on a scale
	-2.12 (0.93)	-2.35 (0.94)	-4.06 (0.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q4W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, baseline score, baseline BCVA of better seeing eye, biomarker status, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8659
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -2.84 to 2.39
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, baseline score, baseline BCVA of better seeing eye, biomarker status, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1399
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-1.94
	Confidence Interval	(2-Sided) 95%; -4.51 to 0.64
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Change From Baseline in NEI VFQ-25 Distance Activity Subscale Score at Week 48
Description	NEI-VFQ-25 questionnaire included 25 items based on which distance activities were measured. Distance activities are defined as reading street signs or names on stores, and going down stairs, steps, or curbs. Response to each question converted to 0-100 score. Subscale=average of items contributing to score. For this subscale the score range is 0 to 100, a higher score represents better functioning. A negative change from baseline indicates a decrease in the distance visual activities; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all the participants who were randomized to the study. Participants analyzed in this outcome measure were those included in MMRM analysis.

Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description:	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Number of Participants Analyzed	239	234	248
Mean (Standard Error); Unit of Measure: score on a scale
	-2.03 (0.99)	-1.04 (1.00)	-3.62 (0.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q4W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, baseline score, baseline BCVA of better seeing eye, biomarker status, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4855
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; -1.79 to 3.76
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, baseline score, baseline BCVA of better seeing eye, biomarker status, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2515
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-1.60
	Confidence Interval	(2-Sided) 95%; -4.33 to 1.13
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Change From Baseline in Mean Functional Reading Independence (FRI) Index at Week 48
Description	The FRI was an interviewer-administered questionnaire with 7 items on functional reading activities most relevant to GA AMD participants. It has one total index score. For each FRI Index reading activity performed in the past 7 days, participants were asked about the extent to which they required vision aids, adjustments in the activity, or help from another participant. Mean FRI Index scores range from 1 to 4, with higher scores indicating greater independence. A negative change from baseline indicates a decrease in the FRI; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all the participants who were randomized to the study. Participants analyzed in this outcome measure were those included in MMRM analysis.

Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description:	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Number of Participants Analyzed	237	230	244
Mean (Standard Error); Unit of Measure: score on a scale
	-0.06 (0.04)	-0.13 (0.04)	-0.15 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q4W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, baseline Mean FRI Index score, baseline BCVA of better seeing eye, biomarker status, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2075
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.18 to 0.04
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator, Lampalizumab Q6W
	Comments	Week 48: MMRM analysis uses change as response variable and included treatment group, baseline Mean FRI Index score, baseline BCVA of better seeing eye, biomarker status, and sex.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1222
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.02
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Up to approximately 2 years
Adverse Event Reporting Description	Safety population included all participants who received at least one dose of study drug.
Arm/Group Title	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
Arm/Group Description	Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
All-Cause Mortality
	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	6/300 (2.00%)	5/298 (1.68%)	6/303 (1.98%)
Serious Adverse Events
	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	97/300 (32.33%)	118/298 (39.60%)	108/303 (35.64%)
Blood and lymphatic system disorders
Anaemia † 1	1/300 (0.33%)	2/298 (0.67%)	0/303 (0.00%)
Haemorrhagic anaemia † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Cardiac disorders
Acute myocardial infarction † 1	1/300 (0.33%)	3/298 (1.01%)	3/303 (0.99%)
Angina pectoris † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Angina unstable † 1	0/300 (0.00%)	1/298 (0.34%)	1/303 (0.33%)
Arrhythmia † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Arteriosclerosis coronary artery † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Atrial fibrillation † 1	3/300 (1.00%)	4/298 (1.34%)	3/303 (0.99%)
Atrial flutter † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Atrioventricular block first degree † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Bradycardia † 1	2/300 (0.67%)	0/298 (0.00%)	2/303 (0.66%)
Cardiac arrest † 1	1/300 (0.33%)	1/298 (0.34%)	0/303 (0.00%)
Cardiac failure † 1	1/300 (0.33%)	3/298 (1.01%)	0/303 (0.00%)
Cardiac failure congestive † 1	2/300 (0.67%)	3/298 (1.01%)	6/303 (1.98%)
Coronary artery disease † 1	4/300 (1.33%)	1/298 (0.34%)	2/303 (0.66%)
Myocardial infarction † 1	0/300 (0.00%)	1/298 (0.34%)	2/303 (0.66%)
Myocardial ischaemia † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Palpitations † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Tachycardia † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Ventricular fibrillation † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Congenital, familial and genetic disorders
Atrial septal defect † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Ear and labyrinth disorders
Vertigo † 1	1/300 (0.33%)	1/298 (0.34%)	1/303 (0.33%)
Eye disorders
Blindness transient † 1	0/300 (0.00%)	2/298 (0.67%)	2/303 (0.66%)
Borderline glaucoma † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Choroidal neovascularisation † 1	2/300 (0.67%)	2/298 (0.67%)	1/303 (0.33%)
Iritis † 1	0/300 (0.00%)	1/298 (0.34%)	1/303 (0.33%)
Neovascular age-related macular degeneration † 1	3/300 (1.00%)	3/298 (1.01%)	3/303 (0.99%)
Open angle glaucoma † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Retinal artery occlusion † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Retinal detachment † 1	1/300 (0.33%)	2/298 (0.67%)	0/303 (0.00%)
Retinal neovascularisation † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Retinal tear † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Visual acuity reduced † 1	10/300 (3.33%)	12/298 (4.03%)	8/303 (2.64%)
Visual acuity reduced transiently † 1	0/300 (0.00%)	2/298 (0.67%)	1/303 (0.33%)
Vitreous haemorrhage † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Vitritis † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Dry age-related macular degeneration † 1	2/300 (0.67%)	0/298 (0.00%)	2/303 (0.66%)
Cataract † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Gastrointestinal disorders
Colitis ischaemic † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Constipation † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Diarrhoea † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Diverticular hernia † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Diverticulum intestinal † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Duodenal ulcer haemorrhage † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Dyspepsia † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Enterocolitis † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Flatulence † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Gastric ulcer † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Gastric volvulus † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Gastritis † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Gastroduodenitis † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Gastrointestinal haemorrhage † 1	1/300 (0.33%)	0/298 (0.00%)	2/303 (0.66%)
Ileus † 1	0/300 (0.00%)	2/298 (0.67%)	0/303 (0.00%)
Inguinal hernia † 1	0/300 (0.00%)	1/298 (0.34%)	1/303 (0.33%)
Oesophagitis ulcerative † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Pancreatitis † 1	0/300 (0.00%)	1/298 (0.34%)	2/303 (0.66%)
Rectal ulcer † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Small intestinal obstruction † 1	2/300 (0.67%)	0/298 (0.00%)	1/303 (0.33%)
Upper gastrointestinal haemorrhage † 1	1/300 (0.33%)	1/298 (0.34%)	0/303 (0.00%)
Gastrointestinal angiectasia † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Obstructive pancreatitis † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Colitis † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
General disorders
Chest pain † 1	1/300 (0.33%)	1/298 (0.34%)	2/303 (0.66%)
Death † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
General physical health deterioration † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Impaired healing † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Pyrexia † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Hepatobiliary disorders
Bile duct stone † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Cholangitis † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Cholecystitis † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Cholelithiasis † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Infections and infestations
Abdominal sepsis † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Bronchitis † 1	0/300 (0.00%)	3/298 (1.01%)	0/303 (0.00%)
Campylobacter infection † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Cellulitis † 1	0/300 (0.00%)	1/298 (0.34%)	1/303 (0.33%)
Cystitis † 1	1/300 (0.33%)	0/298 (0.00%)	2/303 (0.66%)
Device related infection † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Diverticulitis † 1	2/300 (0.67%)	0/298 (0.00%)	1/303 (0.33%)
Endocarditis † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Gastroenteritis † 1	2/300 (0.67%)	1/298 (0.34%)	2/303 (0.66%)
Infection † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Infectious pleural effusion † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Influenza † 1	0/300 (0.00%)	2/298 (0.67%)	0/303 (0.00%)
Perihepatic abscess † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Pneumonia † 1	9/300 (3.00%)	11/298 (3.69%)	5/303 (1.65%)
Pyelonephritis acute † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Sepsis † 1	3/300 (1.00%)	3/298 (1.01%)	2/303 (0.66%)
Septic shock † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Staphylococcal sepsis † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Upper respiratory tract infection † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Urinary tract infection † 1	2/300 (0.67%)	3/298 (1.01%)	1/303 (0.33%)
Viral upper respiratory tract infection † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Conjunctivitis † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Endophthalmitis † 1	0/300 (0.00%)	2/298 (0.67%)	1/303 (0.33%)
Injury, poisoning and procedural complications
Accidental overdose † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Acetabulum fracture † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Ankle fracture † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Comminuted fracture † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Contusion † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Craniocerebral injury † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Dislocation of vertebra † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Fall † 1	5/300 (1.67%)	2/298 (0.67%)	4/303 (1.32%)
Femur fracture † 1	1/300 (0.33%)	4/298 (1.34%)	0/303 (0.00%)
Fibula fracture † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Forearm fracture † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Hip fracture † 1	3/300 (1.00%)	3/298 (1.01%)	3/303 (0.99%)
Humerus fracture † 1	0/300 (0.00%)	2/298 (0.67%)	2/303 (0.66%)
Internal injury † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Lower limb fracture † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Lumbar vertebral fracture † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Muscle rupture † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Pelvic fracture † 1	1/300 (0.33%)	0/298 (0.00%)	1/303 (0.33%)
Post procedural haemorrhage † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Radius fracture † 1	2/300 (0.67%)	0/298 (0.00%)	0/303 (0.00%)
Rib fracture † 1	2/300 (0.67%)	2/298 (0.67%)	1/303 (0.33%)
Road traffic accident † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Spinal compression fracture † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Spinal fracture † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Sternal fracture † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Subdural haematoma † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Upper limb fracture † 1	0/300 (0.00%)	0/298 (0.00%)	2/303 (0.66%)
Corneal abrasion † 1	1/300 (0.33%)	1/298 (0.34%)	0/303 (0.00%)
Facial bones fracture † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Hyphaema † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Cervical vertebral fracture † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Foreign body in eye † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Traumatic intracranial haemorrhage † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Investigations
Blood pressure increased † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Heart rate irregular † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Myocardial necrosis marker increased † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Prostatic specific antigen increased † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Troponin increased † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Intraocular pressure increased † 1	0/300 (0.00%)	16/298 (5.37%)	14/303 (4.62%)
Metabolism and nutrition disorders
Dehydration † 1	2/300 (0.67%)	2/298 (0.67%)	2/303 (0.66%)
Gout † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Hypoglycaemia † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Hypokalaemia † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Hyponatraemia † 1	1/300 (0.33%)	2/298 (0.67%)	0/303 (0.00%)
Iron deficiency † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Malnutrition † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/300 (0.33%)	1/298 (0.34%)	0/303 (0.00%)
Arthritis † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Haemarthrosis † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Intervertebral disc protrusion † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Neuropathic arthropathy † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Osteoarthritis † 1	2/300 (0.67%)	3/298 (1.01%)	2/303 (0.66%)
Rotator cuff syndrome † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Spinal column stenosis † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Spinal osteoarthritis † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Spinal pain † 1	0/300 (0.00%)	2/298 (0.67%)	0/303 (0.00%)
Back pain † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of ureter † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Bladder cancer † 1	0/300 (0.00%)	1/298 (0.34%)	2/303 (0.66%)
Breast cancer † 1	2/300 (0.67%)	1/298 (0.34%)	0/303 (0.00%)
Bronchial carcinoma † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Cholangiocarcinoma † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Endometrial cancer † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Lung adenocarcinoma † 1	0/300 (0.00%)	3/298 (1.01%)	1/303 (0.33%)
Lung cancer metastatic † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Lung neoplasm malignant † 1	0/300 (0.00%)	0/298 (0.00%)	2/303 (0.66%)
Malignant melanoma † 1	2/300 (0.67%)	0/298 (0.00%)	0/303 (0.00%)
Malignant melanoma stage IV † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Malignant pleural effusion † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Meningioma † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Myelodysplastic syndrome † 1	1/300 (0.33%)	0/298 (0.00%)	1/303 (0.33%)
Myxofibrosarcoma † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Neoplasm skin † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Neuroendocrine carcinoma † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Non-small cell lung cancer metastatic † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Oesophageal carcinoma † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Ovarian cancer † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Ovarian cancer metastatic † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Pancreatic carcinoma † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Plasma cell myeloma † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Prostate cancer † 1	1/300 (0.33%)	2/298 (0.67%)	1/303 (0.33%)
Prostate cancer metastatic † 1	0/300 (0.00%)	0/298 (0.00%)	2/303 (0.66%)
Skin cancer † 1	1/300 (0.33%)	0/298 (0.00%)	1/303 (0.33%)
Squamous cell carcinoma † 1	0/300 (0.00%)	2/298 (0.67%)	0/303 (0.00%)
Bladder neoplasm † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Lipoma † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Urethral cancer † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Nervous system disorders
Amyotrophic lateral sclerosis † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Carotid artery stenosis † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Cerebral haematoma † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Cerebral infarction † 1	0/300 (0.00%)	0/298 (0.00%)	2/303 (0.66%)
Cerebral microangiopathy † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Cerebrovascular accident † 1	3/300 (1.00%)	3/298 (1.01%)	1/303 (0.33%)
Cervicogenic vertigo † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Dementia † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Dementia Alzheimer's type † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Dizziness † 1	1/300 (0.33%)	0/298 (0.00%)	1/303 (0.33%)
Dural arteriovenous fistula † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Epilepsy † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Generalised tonic-clonic seizure † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Haemorrhagic stroke † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Headache † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Hemiparesis † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Ischaemic stroke † 1	1/300 (0.33%)	1/298 (0.34%)	0/303 (0.00%)
Lacunar infarction † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Lumbar radiculopathy † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Paraesthesia † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Presyncope † 1	0/300 (0.00%)	2/298 (0.67%)	0/303 (0.00%)
Seizure † 1	1/300 (0.33%)	0/298 (0.00%)	1/303 (0.33%)
Senile dementia † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Transient ischaemic attack † 1	1/300 (0.33%)	4/298 (1.34%)	1/303 (0.33%)
Vertigo CNS origin † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Syncope † 1	2/300 (0.67%)	2/298 (0.67%)	2/303 (0.66%)
Aphasia † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Cognitive disorder † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Embolic stroke † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Psychiatric disorders
Mental status changes † 1	1/300 (0.33%)	1/298 (0.34%)	2/303 (0.66%)
Renal and urinary disorders
Acute kidney injury † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Bladder cyst † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Chronic kidney disease † 1	0/300 (0.00%)	2/298 (0.67%)	0/303 (0.00%)
Dysuria † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Haematuria † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Hydronephrosis † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Nephrolithiasis † 1	1/300 (0.33%)	3/298 (1.01%)	0/303 (0.00%)
Oliguria † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Renal failure † 1	0/300 (0.00%)	2/298 (0.67%)	1/303 (0.33%)
Renal impairment † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Tubulointerstitial nephritis † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Urinary bladder polyp † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Urinary retention † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Reproductive system and breast disorders
Postmenopausal haemorrhage † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Uterovaginal prolapse † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema † 1	0/300 (0.00%)	3/298 (1.01%)	0/303 (0.00%)
Acute respiratory failure † 1	0/300 (0.00%)	0/298 (0.00%)	2/303 (0.66%)
Bronchial hyperreactivity † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Chronic obstructive pulmonary disease † 1	0/300 (0.00%)	3/298 (1.01%)	5/303 (1.65%)
Dyspnoea † 1	1/300 (0.33%)	1/298 (0.34%)	1/303 (0.33%)
Epiglottic cyst † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Epistaxis † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Haemoptysis † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Hypoxia † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Pleural effusion † 1	0/300 (0.00%)	0/298 (0.00%)	2/303 (0.66%)
Pneumonitis † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Pneumothorax † 1	0/300 (0.00%)	1/298 (0.34%)	1/303 (0.33%)
Pneumothorax spontaneous † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Pulmonary air leakage † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Pulmonary embolism † 1	0/300 (0.00%)	2/298 (0.67%)	1/303 (0.33%)
Skin and subcutaneous tissue disorders
Skin ulcer † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Surgical and medical procedures
Cardiac pacemaker battery replacement † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Vascular disorders
Aortic stenosis † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Blood pressure inadequately controlled † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Deep vein thrombosis † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Haematoma † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Hypertension † 1	1/300 (0.33%)	2/298 (0.67%)	0/303 (0.00%)
Hypotension † 1	1/300 (0.33%)	0/298 (0.00%)	2/303 (0.66%)
May-Thurner syndrome † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Peripheral arterial occlusive disease † 1	0/300 (0.00%)	0/298 (0.00%)	1/303 (0.33%)
Peripheral embolism † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
Thrombophlebitis † 1	0/300 (0.00%)	1/298 (0.34%)	0/303 (0.00%)
Orthostatic hypotension † 1	1/300 (0.33%)	0/298 (0.00%)	0/303 (0.00%)
1 Term from vocabulary, MedDRA, version 20.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Sham Comparator	Lampalizumab Q4W	Lampalizumab Q6W
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	221/300 (73.67%)	239/298 (80.20%)	232/303 (76.57%)
Eye disorders
Conjunctival haemorrhage † 1	84/300 (28.00%)	111/298 (37.25%)	93/303 (30.69%)
Eye pain † 1	20/300 (6.67%)	39/298 (13.09%)	33/303 (10.89%)
Vitreous floaters † 1	16/300 (5.33%)	41/298 (13.76%)	25/303 (8.25%)
Vitreous detachment † 1	24/300 (8.00%)	22/298 (7.38%)	24/303 (7.92%)
Dry eye † 1	25/300 (8.33%)	23/298 (7.72%)	14/303 (4.62%)
Cataract † 1	12/300 (4.00%)	22/298 (7.38%)	15/303 (4.95%)
Posterior capsule opacification † 1	14/300 (4.67%)	21/298 (7.05%)	13/303 (4.29%)
Retinal haemorrhage † 1	20/300 (6.67%)	14/298 (4.70%)	17/303 (5.61%)
Punctate keratitis † 1	15/300 (5.00%)	16/298 (5.37%)	16/303 (5.28%)
Gastrointestinal disorders
Nausea † 1	15/300 (5.00%)	10/298 (3.36%)	7/303 (2.31%)
Infections and infestations
Bronchitis † 1	22/300 (7.33%)	29/298 (9.73%)	26/303 (8.58%)
Urinary tract infection † 1	25/300 (8.33%)	26/298 (8.72%)	21/303 (6.93%)
Upper respiratory tract infection † 1	17/300 (5.67%)	14/298 (4.70%)	11/303 (3.63%)
Influenza † 1	12/300 (4.00%)	14/298 (4.70%)	16/303 (5.28%)
Nasopharyngitis † 1	27/300 (9.00%)	45/298 (15.10%)	34/303 (11.22%)
Injury, poisoning and procedural complications
Fall † 1	36/300 (12.00%)	29/298 (9.73%)	34/303 (11.22%)
Investigations
Intraocular pressure increased † 1	9/300 (3.00%)	42/298 (14.09%)	27/303 (8.91%)
Musculoskeletal and connective tissue disorders
Back pain † 1	25/300 (8.33%)	20/298 (6.71%)	14/303 (4.62%)
Arthralgia † 1	11/300 (3.67%)	21/298 (7.05%)	15/303 (4.95%)
Nervous system disorders
Headache † 1	7/300 (2.33%)	20/298 (6.71%)	13/303 (4.29%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	9/300 (3.00%)	16/298 (5.37%)	13/303 (4.29%)
Vascular disorders
Hypertension † 1	14/300 (4.67%)	16/298 (5.37%)	13/303 (4.29%)
1 Term from vocabulary, MedDRA, version 20.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

This study was terminated early by the Sponsor because the compound had demonstrated to lack of efficacy. Thus, not all participants in this study completed the full duration of treatment.

More Information

Certain Agreements

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

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

The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but only after the first publication or presentation that involves the overall study. The Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800 821 - 8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Miere A, Capuano V, Kessler A, Zambrowski O, Jung C, Colantuono D, Pallone C, Semoun O, Petit E, Souied E. Deep learning-based classification of retinal atrophy using fundus autofluorescence imaging. Comput Biol Med. 2021 Mar;130:104198. doi: 10.1016/j.compbiomed.2020.104198. Epub 2020 Dec 28.

Heier JS, Pieramici D, Chakravarthy U, Patel SS, Gupta S, Lotery A, Lad EM, Silverman D, Henry EC, Anderesi M, Tschosik EA, Gray S, Ferrara D, Guymer R; Chroma and Spectri Study Investigators. Visual Function Decline Resulting from Geographic Atrophy: Results from the Chroma and Spectri Phase 3 Trials. Ophthalmol Retina. 2020 Jul;4(7):673-688. doi: 10.1016/j.oret.2020.01.019. Epub 2020 Jan 31.

Holz FG, Sadda SR, Busbee B, Chew EY, Mitchell P, Tufail A, Brittain C, Ferrara D, Gray S, Honigberg L, Martin J, Tong B, Ehrlich JS, Bressler NM; Chroma and Spectri Study Investigators. Efficacy and Safety of Lampalizumab for Geographic Atrophy Due to Age-Related Macular Degeneration: Chroma and Spectri Phase 3 Randomized Clinical Trials. JAMA Ophthalmol. 2018 Jun 1;136(6):666-677. doi: 10.1001/jamaophthalmol.2018.1544.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02247479
• Other Study ID Numbers: GX29176; 2014-000107-27 ( EudraCT Number )
• First Submitted: July 15, 2014
• First Posted: September 25, 2014
• Results First Submitted: January 22, 2019
• Results First Posted: April 23, 2019
• Last Update Posted: June 26, 2019