Trial Outcomes & Findings for A Study Investigating the Safety and Efficacy of Lampalizumab Intravitreal Injections in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (NCT NCT02247531)

Last Updated: 2019-10-15

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

975 participants

Primary outcome timeframe

Baseline, Week 48

Results posted on

2019-10-15

Participant Flow

A total of 975 participants were randomized to the study at 144 study sites across 22 countries. The study was terminated early by the Sponsor due to lack of efficacy.

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.

Participant milestones

Participant milestones
Measure	Sham Comparator Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Overall Study STARTED	321	330	324
Overall Study COMPLETED	215	205	214
Overall Study NOT COMPLETED	106	125	110

Reasons for withdrawal

Reasons for withdrawal
Measure	Sham Comparator Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Overall Study Adverse Event	3	4	9
Overall Study Death	8	9	5
Overall Study Lost to Follow-up	1	8	3
Overall Study Non-compliance	2	2	0
Overall Study Withdrawal by Subject	26	31	25
Overall Study Study Terminated by Sponsor	64	66	62
Overall Study Physician Decision	0	2	2
Overall Study Unspecified Reason	2	3	4

Baseline Characteristics

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).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sham Comparator n=321 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=330 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=324 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.	Total n=975 Participants Total of all reporting groups
Age, Continuous	77.6 years STANDARD_DEVIATION 8.3 • n=321 Participants	77.3 years STANDARD_DEVIATION 7.8 • n=330 Participants	78.7 years STANDARD_DEVIATION 8.0 • n=324 Participants	77.9 years STANDARD_DEVIATION 8.1 • n=975 Participants
Sex: Female, Male Female	191 Participants n=321 Participants	197 Participants n=330 Participants	190 Participants n=324 Participants	578 Participants n=975 Participants
Sex: Female, Male Male	130 Participants n=321 Participants	133 Participants n=330 Participants	134 Participants n=324 Participants	397 Participants n=975 Participants
Race/Ethnicity, Customized Hispanic or Latino	12 Participants n=321 Participants	9 Participants n=330 Participants	16 Participants n=324 Participants	37 Participants n=975 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	298 Participants n=321 Participants	310 Participants n=330 Participants	297 Participants n=324 Participants	905 Participants n=975 Participants
Race/Ethnicity, Customized Not Stated	7 Participants n=321 Participants	8 Participants n=330 Participants	8 Participants n=324 Participants	23 Participants n=975 Participants
Race/Ethnicity, Customized Unknown	7 Participants n=321 Participants	10 Participants n=330 Participants	6 Participants n=324 Participants	23 Participants n=975 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=321 Participants	3 Participants n=330 Participants	1 Participants n=324 Participants	6 Participants n=975 Participants
Race/Ethnicity, Customized Asian	3 Participants n=321 Participants	1 Participants n=330 Participants	1 Participants n=324 Participants	5 Participants n=975 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=321 Participants	1 Participants n=330 Participants	0 Participants n=324 Participants	1 Participants n=975 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants n=321 Participants	0 Participants n=330 Participants	0 Participants n=324 Participants	1 Participants n=975 Participants
Race/Ethnicity, Customized White	306 Participants n=321 Participants	315 Participants n=330 Participants	315 Participants n=324 Participants	936 Participants n=975 Participants
Race/Ethnicity, Customized Multiple	2 Participants n=321 Participants	0 Participants n=330 Participants	1 Participants n=324 Participants	3 Participants n=975 Participants
Geographic Atrophy (GA) Area, as Assessed by Fundus Autofluoresence (FAF)	7.554 millimeter square (mm^2) STANDARD_DEVIATION 3.983 • n=321 Participants	8.308 millimeter square (mm^2) STANDARD_DEVIATION 3.916 • n=330 Participants	8.498 millimeter square (mm^2) STANDARD_DEVIATION 4.260 • n=324 Participants	8.123 millimeter square (mm^2) STANDARD_DEVIATION 4.071 • n=975 Participants
Number of Absolute Scotomatous Points as Assessed by Mesopic Micrometry	23.2 number of absolute scotomatous points STANDARD_DEVIATION 13.5 • n=48 Participants • 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).	28.2 number of absolute scotomatous points STANDARD_DEVIATION 17.3 • n=58 Participants • 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).	27.9 number of absolute scotomatous points STANDARD_DEVIATION 14.4 • n=55 Participants • 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).	26.6 number of absolute scotomatous points STANDARD_DEVIATION 15.3 • n=161 Participants • 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	6.5 decibel (dB) STANDARD_DEVIATION 3.3 • n=48 Participants • 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).	5.7 decibel (dB) STANDARD_DEVIATION 3.8 • n=57 Participants • 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).	5.3 decibel (dB) STANDARD_DEVIATION 3.2 • n=54 Participants • 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).	5.8 decibel (dB) STANDARD_DEVIATION 3.5 • n=159 Participants • 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	66.1 letters STANDARD_DEVIATION 9.8 • n=319 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	66.0 letters STANDARD_DEVIATION 9.6 • n=330 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	65.7 letters STANDARD_DEVIATION 9.8 • n=321 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	66.0 letters STANDARD_DEVIATION 9.7 • n=970 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.
Low Luminance Visual Acuity (LLVA) as Assessed by ETDRS Chart Under Low Luminance Conditions	36.8 letters STANDARD_DEVIATION 16.5 • n=310 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	36.1 letters STANDARD_DEVIATION 17.5 • n=322 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	35.8 letters STANDARD_DEVIATION 16.8 • n=310 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	36.2 letters STANDARD_DEVIATION 16.9 • n=942 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.
Binocular Reading Speed as Assessed by Minnesota Low-Vision Reading Test or Radner Reading Charts	105.16 words per minute (wpm) STANDARD_DEVIATION 56.94 • n=298 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	104.38 words per minute (wpm) STANDARD_DEVIATION 54.35 • n=303 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	99.75 words per minute (wpm) STANDARD_DEVIATION 56.56 • n=302 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	103.09 words per minute (wpm) STANDARD_DEVIATION 55.94 • n=903 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.
Monocular Maximum Reading Speed as Assessed by MNRead Charts or Radner Reading Charts	81.20 wpm STANDARD_DEVIATION 57.48 • n=300 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	80.38 wpm STANDARD_DEVIATION 53.70 • n=310 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	74.52 wpm STANDARD_DEVIATION 50.11 • n=304 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	78.70 wpm STANDARD_DEVIATION 53.85 • n=914 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.
National Eye Institute Visual Functioning Questionnaire 25-item (NEI VFQ-25) Version Composite Score	64.84 score on a scale STANDARD_DEVIATION 15.80 • n=283 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	62.88 score on a scale STANDARD_DEVIATION 17.50 • n=299 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	64.03 score on a scale STANDARD_DEVIATION 17.65 • n=296 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	63.90 score on a scale STANDARD_DEVIATION 17.02 • n=878 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.
NEI VFQ-25 Near Activity Subscale Score	53.89 score on a scale STANDARD_DEVIATION 19.91 • n=283 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	51.68 score on a scale STANDARD_DEVIATION 21.92 • n=299 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	53.24 score on a scale STANDARD_DEVIATION 22.07 • n=296 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	52.92 score on a scale STANDARD_DEVIATION 21.34 • n=878 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.
NEI VFQ-25 Distance Activity Subscale Score	62.68 scores on a scale STANDARD_DEVIATION 21.41 • n=283 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	58.57 scores on a scale STANDARD_DEVIATION 22.03 • n=299 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	60.95 scores on a scale STANDARD_DEVIATION 21.55 • n=296 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	60.70 scores on a scale STANDARD_DEVIATION 21.71 • n=878 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.
Mean Functional Reading Independence (FRI) Index	2.70 score on a scale STANDARD_DEVIATION 0.79 • n=278 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	2.66 score on a scale STANDARD_DEVIATION 0.82 • n=296 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	2.64 score on a scale STANDARD_DEVIATION 0.87 • n=293 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.	2.67 score on a scale STANDARD_DEVIATION 0.83 • n=867 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of participants for whom data were collected.
GA Area in Complement Factor I (CFI) Positive Participants	7.491 mm^2 STANDARD_DEVIATION 4.068 • n=194 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of CFI-positive participants for whom data were collected.	8.183 mm^2 STANDARD_DEVIATION 3.835 • n=199 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of CFI-positive participants for whom data were collected.	8.652 mm^2 STANDARD_DEVIATION 4.250 • n=194 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of CFI-positive participants for whom data were collected.	8.109 mm^2 STANDARD_DEVIATION 4.074 • n=587 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of CFI-positive participants for whom data were collected.
GA Area in CFI Negative Participants	7.650 mm^2 STANDARD_DEVIATION 3.862 • n=127 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of CFI-negative participants for whom data were collected.	8.499 mm^2 STANDARD_DEVIATION 4.044 • n=131 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of CFI-negative participants for whom data were collected.	8.268 mm^2 STANDARD_DEVIATION 4.281 • n=130 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of CFI-negative participants for whom data were collected.	8.144 mm^2 STANDARD_DEVIATION 4.073 • n=388 Participants • ITT population included all the participants who were randomized to the study. Reported here is the number of CFI-negative participants for whom data were collected.

PRIMARY outcome

Timeframe: Baseline, Week 48

Population: Intent-to-treat (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).

Outcome measures

Outcome measures
Measure	Sham Comparator n=291 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=293 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=291 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Change From Baseline in Geographic Atropy (GA) Area, as Assessed by Fundus Autofluoresence (FAF) at Week 48	1.932 millimeter square (mm^2) Standard Error 0.056	2.089 millimeter square (mm^2) Standard Error 0.056	2.019 millimeter square (mm^2) Standard Error 0.056

PRIMARY outcome

Timeframe: Baseline, Week 48

Population: ITT population included all the participants who were randomized to the study. The analysis was done specifically for CFI-positive and negative participants.

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).

Outcome measures

Outcome measures
Measure	Sham Comparator n=321 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=330 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=324 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Change From Baseline in GA Area in Complement Factor I (CFI) Positive and Negative Participants at Week 48 CFI-Positive Participants	2.007 mm^2 Standard Error 0.074	2.057 mm^2 Standard Error 0.072	2.032 mm^2 Standard Error 0.073
Change From Baseline in GA Area in Complement Factor I (CFI) Positive and Negative Participants at Week 48 CFI-Negative Participants	1.809 mm^2 Standard Error 0.087	2.149 mm^2 Standard Error 0.087	1.991 mm^2 Standard Error 0.085

SECONDARY outcome

Timeframe: Baseline, Week 48

Population: 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.

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. Mesopic microperimetry assessments were performed post-dilation on the study eye only, and the data was forwarded to the central reading center. A positive change from baseline indicates an increase in the number of absolute scotomatous points (more lack of retinal sensitivity); disease worsening. Data were collected up to Week 48 instead of Week 96, due to early termination of the study.

Outcome measures

Outcome measures
Measure	Sham Comparator n=39 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=42 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=43 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Change From Baseline in Number of Absolute Scotomatous Points Assessed by Mesopic Microperimetry at Week 48	5.4 number of absolute scotomatous points Standard Error 1.6	5.0 number of absolute scotomatous points Standard Error 1.5	6.7 number of absolute scotomatous points Standard Error 1.5

SECONDARY outcome

Timeframe: Baseline, Week 48

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. Data were collected up to Week 48 instead of Week 96, due to early termination of the study.

Outcome measures

Outcome measures
Measure	Sham Comparator n=39 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=41 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=42 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Change From Baseline in Macular Sensitivity as Assessed by Mesopic Microperimetry at Week 48	-0.99 decibel (dB) Standard Error 0.36	-0.89 decibel (dB) Standard Error 0.34	-1.25 decibel (dB) Standard Error 0.35

SECONDARY outcome

Timeframe: Baseline, Week 48

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

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). A decrease in the VA score indicates a worsening in visual acuity. BCVA score testing was performed prior to dilating the eyes. The data was collected up to Week 48 instead of Week 96, due to early termination of the study. 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.

Outcome measures

Outcome measures
Measure	Sham Comparator n=288 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=286 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=287 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Change From Baseline in Best Corrected Visual Acuity (BCVA) Score as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart at Week 48	-5.3 letters Standard Error 0.7	-4.6 letters Standard Error 0.7	-5.1 letters Standard Error 0.7

SECONDARY outcome

Timeframe: Week 48

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

Loss of less than 15 letters from baseline was assessed by the ETDRS chart at a starting distance of 4 meters (m). Data were collected up to Week 48 instead of Week 96, due to early termination of the study.

Outcome measures

Outcome measures
Measure	Sham Comparator n=288 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=286 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=287 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Percentage of Participants With Less Than 15 Letters Loss From Baseline in BCVA Score at Week 48	87.1 percentage of participants	88.2 percentage of participants	86.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 48

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

The low luminance visual acuity 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. A negative change from baseline indicates a decrease in the visual acuity; disease worsening. Data were collected up to Week 48 instead of Week 96, due to early termination of the study.

Outcome measures

Outcome measures
Measure	Sham Comparator n=274 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=278 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=274 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Change From Baseline in Low Luminance Visual Acuity (LLVA) as Assessed by ETDRS Chart Under Low Luminance Conditions at Week 48	-2.5 letters Standard Error 0.6	-2.6 letters Standard Error 0.6	-3.6 letters Standard Error 0.6

SECONDARY outcome

Timeframe: Week 48

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

Loss of less than 15 letters from baseline was assessed by the ETDRS chart at a starting distance of 4 m. Data were collected up to Week 48 instead of Week 96, due to early termination of the study.

Outcome measures

Outcome measures
Measure	Sham Comparator n=274 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=278 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=274 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Percentage of Participants With Less Than 15 Letters Loss From Baseline in LLVA Score at Week 48	90.1 percentage of participants Interval 83.7 to 91.5	92.1 percentage of participants Interval 86.4 to 93.5	89.6 percentage of participants Interval 82.9 to 90.9

SECONDARY outcome

Timeframe: Baseline, Week 48

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

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. Data were collected up to Week 48 instead of Week 96, due to early termination of the study.

Outcome measures

Outcome measures
Measure	Sham Comparator n=261 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=255 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=266 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Change From Baseline in Binocular Reading Speed as Assessed by Minnesota Low-Vision Reading Test (MNRead) Charts or Radner Reading Charts at Week 48	-15.27 words per minute (wpm) Standard Error 2.33	-13.92 words per minute (wpm) Standard Error 2.36	-14.20 words per minute (wpm) Standard Error 2.31

SECONDARY outcome

Timeframe: Baseline, Week 48

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

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. 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.

Outcome measures

Outcome measures
Measure	Sham Comparator n=264 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=264 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=272 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Change From Baseline in Monocular Maximum Reading Speed as Assessed by MNRead Charts or Radner Reading Charts at Week 48	-16.58 wpm Standard Error 2.30	-16.46 wpm Standard Error 2.30	-18.30 wpm Standard Error 2.27

SECONDARY outcome

Timeframe: Baseline, Week 48

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

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 or total score is the average of items contributing to the score. For each subscale and total score the score range is 0 to 100 with a higher score representing better functioning. A negative change from baseline indicates a decrease in the visual functioning; disease worsening. Data were collected up to Week 48 instead of Week 96, due to early termination of the study.

Outcome measures

Outcome measures
Measure	Sham Comparator n=251 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=259 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=265 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Change From Baseline in National Eye Institute Visual Functioning Questionnaire 25-item (NEI VFQ-25) Version Composite Score at Week 48	-2.08 score on a scale Standard Error 0.74	-0.86 score on a scale Standard Error 0.73	-1.05 score on a scale Standard Error 0.72

SECONDARY outcome

Timeframe: Baseline, Week 48

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

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.

Outcome measures

Outcome measures
Measure	Sham Comparator n=251 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=259 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=265 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Change From Baseline in NEI VFQ-25 Near Activity Subscale Score at Week 48	-4.12 score on a scale Standard Error 0.91	-1.49 score on a scale Standard Error 0.89	-1.93 score on a scale Standard Error 0.88

SECONDARY outcome

Timeframe: Baseline, Week 48

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

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.

Outcome measures

Outcome measures
Measure	Sham Comparator n=251 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=259 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=265 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Change From Baseline in NEI VFQ-25 Distance Activity Subscale Score at Week 48	-2.83 score on a scale Standard Error 1.04	-1.80 score on a scale Standard Error 1.03	-2.24 score on a scale Standard Error 1.01

SECONDARY outcome

Timeframe: Baseline, Week 48

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

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.

Outcome measures

Outcome measures
Measure	Sham Comparator n=248 Participants Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=257 Participants Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=260 Participants Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Change From Baseline in Mean Functional Reading Independence (FRI) Index at Week 48	-0.16 score on a scale Standard Error 0.04	-0.12 score on a scale Standard Error 0.04	-0.14 score on a scale Standard Error 0.04

Adverse Events

Sham Comparator

Serious events: 99 serious events

Other events: 227 other events

Deaths: 9 deaths

Lampalizumab Q4W

Serious events: 113 serious events

Other events: 268 other events

Deaths: 10 deaths

Lampalizumab Q6W

Serious events: 111 serious events

Other events: 253 other events

Deaths: 7 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Sham Comparator n=318 participants at risk Participants received sham comparator, once every 4 weeks (Q4W) starting at the Day 1 visit or once every 6 weeks (Q6W) starting at the Day 1 visit.	Lampalizumab Q4W n=329 participants at risk Participants received 10 mg (milligrams) dose of lampalizumab by intravitreal injection Q4W starting at the Day 1 visit.	Lampalizumab Q6W n=323 participants at risk Participants received 10 mg dose of lampalizumab by intravitreal injection Q6W starting at the Day 1 visit.
Eye disorders Conjunctival haemorrhage	26.4% 84/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	34.0% 112/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	30.0% 97/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Eye pain	9.4% 30/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	16.7% 55/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	11.1% 36/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Vitreous detachment	7.5% 24/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	11.2% 37/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	9.6% 31/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Cataract	7.9% 25/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	7.0% 23/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	7.7% 25/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Retinal haemorrhage	4.4% 14/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	7.3% 24/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	6.8% 22/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Dry eye	5.0% 16/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	5.8% 19/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	5.0% 16/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Vitreous floaters	1.6% 5/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	8.8% 29/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	8.0% 26/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Blepharitis	3.5% 11/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	7.9% 26/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.6% 15/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Vision blurred	4.7% 15/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	5.5% 18/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	3.7% 12/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Posterior capsule opacification	3.5% 11/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	6.1% 20/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	3.4% 11/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	1.6% 5/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	5.5% 18/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	2.5% 8/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	14.5% 46/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	13.7% 45/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	11.1% 36/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	6.9% 22/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	10.0% 33/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.3% 14/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Infections and infestations Bronchitis	5.0% 16/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	7.6% 25/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	9.9% 32/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	6.3% 20/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	5.8% 19/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.0% 13/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Infections and infestations Influenza	4.1% 13/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	7.0% 23/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.3% 14/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fall	12.9% 41/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	14.3% 47/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	8.7% 28/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Investigations Intraocular pressure increased	2.2% 7/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	15.2% 50/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	12.1% 39/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	5.3% 17/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	6.7% 22/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.3% 14/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	5.0% 16/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	5.5% 18/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.3% 14/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Nervous system disorders Headache	3.5% 11/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	6.1% 20/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	2.8% 9/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	3.1% 10/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	7.9% 26/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	3.1% 10/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Vascular disorders Hypertension	8.2% 26/318 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	8.2% 27/329 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	6.8% 22/323 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.