Trial Outcomes & Findings for A Study Investigating the Efficacy and Safety of Lampalizumab Intravitreal Injections in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (NCT NCT02247479)

Last Updated: 2019-06-26

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

906 participants

Primary outcome timeframe

Baseline, Week 48

Results posted on

2019-06-26

Participant Flow

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.

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 in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Study STARTED	305	298	303
Overall Study COMPLETED	163	160	165
Overall Study NOT COMPLETED	142	138	138

Reasons for withdrawal

Reasons for withdrawal
Measure	Sham Comparator Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Overall Study Adverse Event	8	9	8
Overall Study Death	5	4	6
Overall Study Lost to Follow-up	3	3	1
Overall Study Non-compliance	0	0	1
Overall Study Withdrawal by Subject	25	29	24
Overall Study Study Terminated by Sponsor	98	88	94
Overall Study Physician Decision	1	0	2
Overall Study Unspecified Reason	2	5	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sham Comparator n=305 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=298 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=303 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.	Total n=906 Participants Total of all reporting groups
Age, Continuous	78.5 years STANDARD_DEVIATION 7.8 • n=305 Participants	77.5 years STANDARD_DEVIATION 7.9 • n=298 Participants	78.3 years STANDARD_DEVIATION 8.5 • n=303 Participants	78.1 years STANDARD_DEVIATION 8.1 • n=906 Participants
Sex: Female, Male Female	186 Participants n=305 Participants	182 Participants n=298 Participants	185 Participants n=303 Participants	553 Participants n=906 Participants
Sex: Female, Male Male	119 Participants n=305 Participants	116 Participants n=298 Participants	118 Participants n=303 Participants	353 Participants n=906 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=305 Participants	1 Participants n=298 Participants	1 Participants n=303 Participants	2 Participants n=906 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=305 Participants	1 Participants n=298 Participants	0 Participants n=303 Participants	1 Participants n=906 Participants
Race/Ethnicity, Customized White	302 Participants n=305 Participants	294 Participants n=298 Participants	295 Participants n=303 Participants	891 Participants n=906 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=305 Participants	0 Participants n=298 Participants	1 Participants n=303 Participants	1 Participants n=906 Participants
Race/Ethnicity, Customized Unknown	4 Participants n=305 Participants	0 Participants n=298 Participants	2 Participants n=303 Participants	6 Participants n=906 Participants
Race/Ethnicity, Customized Hispanic or Latino	20 Participants n=305 Participants	17 Participants n=298 Participants	18 Participants n=303 Participants	55 Participants n=906 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	279 Participants n=305 Participants	278 Participants n=298 Participants	282 Participants n=303 Participants	839 Participants n=906 Participants
Race/Ethnicity, Customized Not Stated	2 Participants n=305 Participants	3 Participants n=298 Participants	1 Participants n=303 Participants	6 Participants n=906 Participants
Geographic Atrophy (GA) Area, as Assessed by Fundus Autofluoresence (FAF)	7.953 millimeter square (mm^2) STANDARD_DEVIATION 3.925 • n=305 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	7.910 millimeter square (mm^2) STANDARD_DEVIATION 3.887 • n=298 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	8.116 millimeter square (mm^2) STANDARD_DEVIATION 4.236 • n=302 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	7.993 millimeter square (mm^2) STANDARD_DEVIATION 4.016 • n=905 Participants • 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	29.1 absolute scotomatous points STANDARD_DEVIATION 16.8 • n=44 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).	25.2 absolute scotomatous points STANDARD_DEVIATION 13.4 • n=33 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).	20.5 absolute scotomatous points STANDARD_DEVIATION 13.4 • n=39 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).	25.1 absolute scotomatous points STANDARD_DEVIATION 15.1 • n=116 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	5.40 decibel (dB) STANDARD_DEVIATION 3.37 • n=44 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).	6.37 decibel (dB) STANDARD_DEVIATION 4.02 • n=33 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).	7.38 decibel (dB) STANDARD_DEVIATION 3.40 • n=39 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).	6.34 decibel (dB) STANDARD_DEVIATION 3.64 • n=116 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	65.9 letters STANDARD_DEVIATION 9.9 • n=301 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	66.1 letters STANDARD_DEVIATION 10.0 • n=295 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	66.4 letters STANDARD_DEVIATION 10.1 • n=301 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	66.2 letters STANDARD_DEVIATION 10.0 • n=897 Participants • 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	36.0 letters STANDARD_DEVIATION 15.7 • n=299 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	36.9 letters STANDARD_DEVIATION 17.8 • n=287 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	36.2 letters STANDARD_DEVIATION 16.7 • n=293 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	36.4 letters STANDARD_DEVIATION 16.7 • n=879 Participants • 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	106.89 words per minute (wpm) STANDARD_DEVIATION 57.98 • n=278 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	109.18 words per minute (wpm) STANDARD_DEVIATION 60.14 • n=262 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	104.22 words per minute (wpm) STANDARD_DEVIATION 62.37 • n=269 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	106.74 words per minute (wpm) STANDARD_DEVIATION 60.12 • n=809 Participants • 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	66.16 score on a scale STANDARD_DEVIATION 17.33 • n=276 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	64.80 score on a scale STANDARD_DEVIATION 16.12 • n=275 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	65.19 score on a scale STANDARD_DEVIATION 17.27 • n=282 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	65.38 score on a scale STANDARD_DEVIATION 16.91 • n=833 Participants • 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	2.69 score on a scale STANDARD_DEVIATION 0.83 • n=276 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	2.71 score on a scale STANDARD_DEVIATION 0.79 • n=273 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	2.70 score on a scale STANDARD_DEVIATION 0.82 • n=280 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	2.70 score on a scale STANDARD_DEVIATION 0.81 • n=829 Participants • 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	54.98 score on a scale STANDARD_DEVIATION 20.98 • n=276 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	53.78 score on a scale STANDARD_DEVIATION 20.56 • n=275 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	53.67 score on a scale STANDARD_DEVIATION 22.21 • n=282 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	54.14 score on a scale STANDARD_DEVIATION 21.25 • n=833 Participants • 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	62.86 score on a scale STANDARD_DEVIATION 21.46 • n=276 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	60.97 score on a scale STANDARD_DEVIATION 20.48 • n=275 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	62.10 score on a scale STANDARD_DEVIATION 22.16 • n=282 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	61.98 score on a scale STANDARD_DEVIATION 21.37 • n=833 Participants • 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	80.89 wpm STANDARD_DEVIATION 52.95 • n=278 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	85.18 wpm STANDARD_DEVIATION 54.55 • n=265 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	79.49 wpm STANDARD_DEVIATION 54.23 • n=271 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	81.82 wpm STANDARD_DEVIATION 53.89 • n=814 Participants • 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	8.015 mm^2 STANDARD_DEVIATION 3.915 • n=181 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	8.152 mm^2 STANDARD_DEVIATION 4.118 • n=176 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	8.406 mm^2 STANDARD_DEVIATION 4.399 • n=177 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	8.190 mm^2 STANDARD_DEVIATION 4.142 • n=534 Participants • 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	7.864 mm^2 STANDARD_DEVIATION 3.952 • n=124 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	7.560 mm^2 STANDARD_DEVIATION 3.515 • n=122 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	7.705 mm^2 STANDARD_DEVIATION 3.975 • n=125 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.	7.710 mm^2 STANDARD_DEVIATION 3.814 • n=371 Participants • ITT population included all the participants who were randomized to the study. Reported here are the number of participants for whom data was collected.

PRIMARY 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 Mixed-effect model repeated measures (MMRM) analysis.

Outcome measures

Outcome measures
Measure	Sham Comparator n=274 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=259 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=270 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Change From Baseline in Geographic Atrophy (GA) Area, as Assessed by Fundus Autofluoresence (FAF) at Week 48	2.035 millimeter square (mm^2) Standard Error 0.066	2.016 millimeter square (mm^2) Standard Error 0.068	2.086 millimeter square (mm^2) Standard Error 0.067

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. Number analyzed for each row signifies the participants evaluated for specified categories for each reporting group.

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=305 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=298 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=303 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Change From Baseline in GA Area in Complement Factor I (CFI) Positive and Negative Participants at Week 48 CFI-Positive Participants	2.067 mm^2 Standard Error 0.086	2.045 mm^2 Standard Error 0.089	2.144 mm^2 Standard Error 0.087
Change From Baseline in GA Area in Complement Factor I (CFI) Positive and Negative Participants at Week 48 CFI-Negative Participants	2.006 mm^2 Standard Error 0.103	1.974 mm^2 Standard Error 0.105	2.012 mm^2 Standard Error 0.104

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, 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.

Outcome measures

Outcome measures
Measure	Sham Comparator n=30 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=26 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=26 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Change From Baseline in Number of Absolute Scotomatous Points as Assessed by Mesopic Micrometry at Week 48	8.3 absolute scotomatous points Standard Error 1.7	8.1 absolute scotomatous points Standard Error 1.8	8.3 absolute scotomatous points Standard Error 1.8

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. 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=30 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=26 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=26 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Change From Baseline in Mean Macular Sensitivity as Assessed by Mesopic Microperimetry at Week 48	-1.61 decibel (dB) Standard Error 0.33	-1.33 decibel (dB) Standard Error 0.34	-2.24 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). 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.

Outcome measures

Outcome measures
Measure	Sham Comparator n=267 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=259 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=261 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at 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	-4.5 letters Standard Error 0.6	-3.4 letters Standard Error 0.6	-4.6 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 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.

Outcome measures

Outcome measures
Measure	Sham Comparator n=267 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=259 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=262 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Percentage of Participants With Less Than 15 Letters Loss From Baseline in BCVA Score at Week 48	85.8 percentage of participants Interval 81.6 to 90.0	88.8 percentage of participants Interval 85.0 to 92.6	87.0 percentage of participants Interval 83.0 to 91.1

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 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.

Outcome measures

Outcome measures
Measure	Sham Comparator n=265 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=251 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=252 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Change From Baseline in Low Luminance Visual Acuity (LLVA) as Assessed by ETDRS Chart Under Low Luminance Conditions at Week 48	-3.0 letters Standard Error 0.7	-2.4 letters Standard Error 0.7	-2.7 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 m. 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=265 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=251 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=253 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Percentage of Participants With Less Than 15 Letters Loss From Baseline in LLVA Score at Week 48	86.8 percentage of participants Interval 82.7 to 90.9	85.3 percentage of participants Interval 80.9 to 89.6	86.6 percentage of participants Interval 82.4 to 90.8

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. 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=242 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=223 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=229 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at 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	-18.97 words per minute (wpm) Standard Error 2.37	-13.32 words per minute (wpm) Standard Error 2.47	-19.96 words per minute (wpm) Standard Error 2.44

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 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=243 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=229 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=233 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Change From Baseline in Monocular Maximum Reading Speed as Assessed by MNRead Charts or Radner Reading Charts at Week 48	-19.63 wpm Standard Error 2.41	-17.91 wpm Standard Error 2.49	-18.16 wpm Standard Error 2.47

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, 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.

Outcome measures

Outcome measures
Measure	Sham Comparator n=239 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=234 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=248 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Change From Baseline in National Eye Institute Visual Functioning Questionnaire 25-item (NEI VFQ-25) Version Composite Score at Week 48	-1.31 scores on a scale Standard Error 0.71	-1.66 scores on a scale Standard Error 0.72	-2.87 scores on a scale Standard Error 0.70

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=239 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=234 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=248 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Change From Baseline in NEI VFQ-25 Near Activity Subscale Score at Week 48	-2.12 score on a scale Standard Error 0.93	-2.35 score on a scale Standard Error 0.94	-4.06 score on a scale Standard Error 0.92

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=239 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=234 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=248 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Change From Baseline in NEI VFQ-25 Distance Activity Subscale Score at Week 48	-2.03 score on a scale Standard Error 0.99	-1.04 score on a scale Standard Error 1.00	-3.62 score on a scale Standard Error 0.97

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=237 Participants Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=230 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=244 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Change From Baseline in Mean Functional Reading Independence (FRI) Index at Week 48	-0.06 score on a scale Standard Error 0.04	-0.13 score on a scale Standard Error 0.04	-0.15 score on a scale Standard Error 0.04

Adverse Events

Sham Comparator

Serious events: 97 serious events

Other events: 221 other events

Deaths: 6 deaths

Lampalizumab Q4W

Serious events: 118 serious events

Other events: 239 other events

Deaths: 5 deaths

Lampalizumab Q6W

Serious events: 108 serious events

Other events: 232 other events

Deaths: 6 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=300 participants at risk Participants received sham comparator once in every 4 weeks (Q4W) or once in every 6 weeks (Q6W) starting at Day 1 visit.	Lampalizumab Q4W n=298 participants at risk Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q4W starting at Day 1 visit.	Lampalizumab Q6W n=303 participants at risk Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q6W starting at Day 1 visit.
Eye disorders Conjunctival haemorrhage	28.0% 84/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	37.2% 111/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	30.7% 93/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Eye pain	6.7% 20/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	13.1% 39/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	10.9% 33/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Vitreous floaters	5.3% 16/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	13.8% 41/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	8.3% 25/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Vitreous detachment	8.0% 24/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	7.4% 22/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	7.9% 24/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Dry eye	8.3% 25/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	7.7% 23/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.6% 14/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Cataract	4.0% 12/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	7.4% 22/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	5.0% 15/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Posterior capsule opacification	4.7% 14/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	7.0% 21/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.3% 13/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Investigations Intraocular pressure increased	3.0% 9/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	14.1% 42/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	8.9% 27/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	5.0% 15/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	3.4% 10/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	2.3% 7/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Infections and infestations Bronchitis	7.3% 22/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	9.7% 29/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	8.6% 26/303 • 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	12.0% 36/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	9.7% 29/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	11.2% 34/303 • 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	8.3% 25/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	6.7% 20/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.6% 14/303 • 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	3.7% 11/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	7.0% 21/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	5.0% 15/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Nervous system disorders Headache	2.3% 7/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	6.7% 20/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.3% 13/303 • 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	3.0% 9/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	5.4% 16/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.3% 13/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Vascular disorders Hypertension	4.7% 14/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	5.4% 16/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.3% 13/303 • 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	8.3% 25/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	8.7% 26/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	6.9% 21/303 • 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	5.7% 17/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.7% 14/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	3.6% 11/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Infections and infestations Influenza	4.0% 12/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.7% 14/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	5.3% 16/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Retinal haemorrhage	6.7% 20/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	4.7% 14/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	5.6% 17/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Eye disorders Punctate keratitis	5.0% 15/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	5.4% 16/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	5.3% 16/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	9.0% 27/300 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	15.1% 45/298 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.	11.2% 34/303 • Up to approximately 2 years Safety population included all participants who received at least one dose of study drug.