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Clinical Trial Results:
A Phase III, Multicenter, Randomized, Double-Masked, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of Faricimab in Patients with Macular Edema Secondary to Branch Retinal Vein Occlusion

Summary
EudraCT number	2020-000440-63
Trial protocol	HU DE PT AT CZ PL IT
Global end of trial date	12 Jun 2023

Results information
Results version number	v2(current)
This version publication date	04 Sep 2024
First version publication date	26 Jun 2024
Other versions	v1
Version creation reason	Correction of full data set There are a few small corrections that need to be made to the results record.

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

GR41984

ISRCTN number

US NCT number

NCT04740905

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche, Ltd.

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, 4058

Public contact

F. Hoffmann-La Roche, Ltd., F. Hoffmann-La Roche, Ltd., +41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche, Ltd., F. Hoffmann-La Roche, Ltd., +41 616878333, global.trial_information@roche.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

12 Jun 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

12 Jun 2023

Was the trial ended prematurely?

Main objective of the trial

The primary efficacy objective for this study is to evaluate the efficacy of faricimab 6 mg IVT Q4W compared with aflibercept 2 mg IVT Q4W on the basis of the change from baseline in BCVA at Week 24.

Protection of trial subjects

This study was conducted in full conformance with the ICH E6 guideline for Good Clinical Practice and the principles of the Declaration of Helsinki, or the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the individual. All participants were required to read and sign an informed consent form prior to participation in the study.

Background therapy

Evidence for comparator

Actual start date of recruitment

02 Mar 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 68

Country: Number of subjects enrolled

Australia: 14

Country: Number of subjects enrolled

Austria: 3

Country: Number of subjects enrolled

Brazil: 8

Country: Number of subjects enrolled

China: 63

Country: Number of subjects enrolled

Czechia: 18

Country: Number of subjects enrolled

France: 3

Country: Number of subjects enrolled

Germany: 9

Country: Number of subjects enrolled

Hong Kong: 8

Country: Number of subjects enrolled

Hungary: 15

Country: Number of subjects enrolled

Israel: 15

Country: Number of subjects enrolled

Italy: 7

Country: Number of subjects enrolled

Japan: 34

Country: Number of subjects enrolled

Korea, Republic of: 48

Country: Number of subjects enrolled

Poland: 47

Country: Number of subjects enrolled

Portugal: 9

Country: Number of subjects enrolled

Russian Federation: 17

Country: Number of subjects enrolled

Singapore: 3

Country: Number of subjects enrolled

Spain: 14

Country: Number of subjects enrolled

Taiwan: 14

Country: Number of subjects enrolled

United Kingdom: 10

Country: Number of subjects enrolled

United States: 126

Worldwide total number of subjects

553

EEA total number of subjects

125

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

277

From 65 to 84 years

262

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 768 patients were screened; 9 of these patients were rescreened and randomized in the study. A total of 215 patients failed screening due to not meeting the inclusion criteria. A total of 553 patients with BRVO were randomized 1:1 into the study: 276 to the faricimab Q4W arm and 277 to the aflibercept Q4W arm.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst, Assessor

Are arms mutually exclusive

Yes

Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)

Arm description

In Part 1 (Day 1 through Week 24), participants were randomly assigned to Arm A to receive faricimab 6 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants received faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure was administered during study visits at which no faricimab treatment was administered (according to the PTI dosing regimen).

Arm type

Experimental

Investigational medicinal product name

Faricimab

Investigational medicinal product code

RO6867461

Other name

VABYSMO®

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

Patients randomly assigned to Arm A received 6 mg faricimab intravitreal injections once every 4 weeks (Q4W) from Day 1 through Week 20 (6 injections) in Part 1 of the study. In Part 2 of the study, patients in Arm A switched from faricimab Q4W to receive 6 mg faricimab intravitreal injections according to a personalized treatment interval (PTI) dosing regimen from Week 24 through Week 68.

Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)

Arm description

In Part 1 (Day 1 through Week 24), participants were randomly assigned to Arm B to receive aflibercept 2 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants received faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure was to be administered during study visits at which no faricimab treatment was administered (according to the PTI dosing regimen).

Arm type

Active comparator

Investigational medicinal product name

Faricimab

Investigational medicinal product code

RO6867461

Other name

VABYSMO®

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

In Part 2 of the study, patients in Arm B switched from aflibercept to receive 6 mg faricimab intravitreal injections according to a personalized treatment interval (PTI) dosing regimen from Week 24 through Week 68.

Investigational medicinal product name

Aflibercept

Investigational medicinal product code

Other name

Eylea

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

Patients randomly assigned to Arm B received 2 mg aflibercept intravitreal injections once every 4 weeks (Q4W) from Day 1 through Week 20 (6 injections) in Part 1 of the study.

Number of subjects in period 1	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Started	276	277
Received ≥1 Dose of Study Drug (Part 1)	276	274
Completed Part 1	272	274
Started Part 2	272	274
Completed	245	244
Not completed	31	33
Adverse event, serious fatal	2	2
Consent withdrawn by subject	14	12
Physician decision	-	4
Adverse event, non-fatal	1	4
Did Not Return to Hospital Due to COVID19 Epidemic	1	-
Non-Compliance With Study Drug	2	1
Lost to follow-up	9	6
Patient Refused to Continue Study	1	-
Patient Missed Week 72 Visit Due to SAE	1	1
Protocol deviation	-	3

Baseline characteristics

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Reporting group title

Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)

Reporting group description

Reporting group title

Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)

Reporting group description

Reporting group values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)	Total
Number of subjects	276	277	553
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	133	144	277
From 65-84 years	133	129	262
85 years and over	10	4	14
Age Continuous
Units: Years
arithmetic mean (standard deviation)	64.3 ( 10.7 )	63.8 ( 10.6 )	-
Sex: Female, Male
Units: Participants
Female	133	147	280
Male	143	130	273
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	3	0	3
Asian	90	94	184
Native Hawaiian or Other Pacific Islander	1	0	1
Black or African American	6	7	13
White	172	172	344
More than one race	0	0	0
Unknown or Not Reported	4	4	8
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	47	51	98
Not Hispanic or Latino	224	224	448
Unknown or Not Reported	5	2	7
Region of Enrollment
Units: Subjects
Rest of the World	129	128	257
Asia	85	85	170
USA and Canada	62	64	126
Number of Participants by the Eye (Left or Right) Chosen as the Study Eye
Units: Subjects
Left Eye	140	127	267
Right Eye	136	150	286
Number of Participants by the BCVA Letter Score Categories in the Study Eye
Units: Subjects
≤54 Letters (20/80 or Worse)	89	90	179
≥55 Letters (20/80 or Better)	187	187	374
Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye
Units: ETDRS Letters
arithmetic mean (standard deviation)	57.50 ( 13.04 )	57.64 ( 12.15 )	-

End points

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Reporting group title

Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)

Reporting group description

Reporting group title

Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)

Reporting group description

Subject analysis set title

Arm A: Faricimab Q4W (Part 1)

Subject analysis set type

Intention-to-treat

Subject analysis set description

In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm A were to receive faricimab 6 milligrams (mg) administered by intravitreal (IVT) injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections).

Subject analysis set title

Arm B: Aflibercept Q4W (Part 1)

Subject analysis set type

Intention-to-treat

Subject analysis set description

In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm B were to receive aflibercept 2 milligrams (mg) administered by intravitreal (IVT) injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections).

Subject analysis set title

Arm A: Faricimab Q4W to Faricimab PTI (Part 2)

Subject analysis set type

Intention-to-treat

Subject analysis set description

In Part 2 (from Week 24 to Week 72), participants received faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure was administered during study visits at which no faricimab treatment was administered (according to the PTI dosing regimen).

Subject analysis set title

Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)

Subject analysis set type

Intention-to-treat

Subject analysis set description

In Part 2 (from Week 24 to Week 72), participants received faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure was to be administered during study visits at which no faricimab treatment was administered (according to the PTI dosing regimen).

Subject analysis set title

Arm A: Faricimab Q4W to Faricimab PTI (Part 2)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)

Subject analysis set type

Intention-to-treat

Subject analysis set description

In Part 2 (from Week 24 to Week 72), participants received faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure was to be administered during study visits at which no faricimab treatment was administered (according to the PTI dosing regimen).

Subject analysis set title

Arm B: Aflibercept Q4W (Part 1)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Arm A: Faricimab Q4W to Faricimab PTI (Part 2)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)

Subject analysis set type

Safety analysis

Subject analysis set description

In Part 2 (from Week 24 to Week 72), participants received faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure was to be administered during study visits at which no faricimab treatment was administered (according to the PTI dosing regimen).

Subject analysis set title

All Faricimab Participants

Subject analysis set type

Safety analysis

Subject analysis set description

This immunogenicity analysis group represents all participants with an evaluable ADA sample. At baseline, evaluable participants were those with an ADA sample prior to faricimab injection, including those who did not receive study treatment; post-baseline, evaluable participants were those with an ADA sample after having received at least one dose of faricimab.

Primary: Part 1: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye at Week 24

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End point title

Part 1: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye at Week 24

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), and randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.

End point type

Primary

End point timeframe

From Baseline through Week 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: ETDRS Letters
arithmetic mean (confidence interval 95%)	16.9 (15.7 to 18.1)	17.5 (16.3 to 18.6)

BCVA Non-inferiority

Statistical analysis description

The null hypothesis, H0: μ(faricimab) − μ(aflibercept) ≤−4 letters; the alternative hypothesis, Ha: μ(faricimab) − μ(aflibercept) >−4 letters. The final sample size provided >90% power for the non-inferiority assessment (at a one-sided 0.02485 significance level).

Comparison groups

Arm A: Faricimab Q4W (Part 1) v Arm B: Aflibercept Q4W (Part 1)

Number of subjects included in analysis

553

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

Method

Parameter type

Difference in Adjusted Means

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.84

Notes
[1] - If the lower bound of a two-sided 95% confidence interval (CI) for the difference in adjusted means of the two treatments (faricimab minus aflibercept) is greater than -4 letters (the non-inferiority margin), then faricimab is considered non-inferior to aflibercept.

BCVA Superiority

Statistical analysis description

The final sample size provided >80% power for a 3.5-letter superiority assessment of faricimab over aflibercept.

Comparison groups

Arm A: Faricimab Q4W (Part 1) v Arm B: Aflibercept Q4W (Part 1)

Number of subjects included in analysis

553

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4978 ^[2]

Method

Mixed Model of Repeated Measures

Parameter type

Difference in Adjusted Means

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.84

Notes
[2] - Tested at a two-sided 0.0497 significance level.

Secondary: Part 1: Change from Baseline in BCVA in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Change from Baseline in BCVA in the Study Eye at Specified Timepoints Through Week 24

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: ETDRS Letters
arithmetic mean (confidence interval 95%)
Week 4	11.5 (10.5 to 12.5)	12.4 (11.4 to 13.4)
Week 8	13.7 (12.6 to 14.7)	15.1 (14.1 to 16.2)
Week 12	15.1 (14.0 to 16.2)	15.9 (14.8 to 17.0)
Week 16	15.5 (14.4 to 16.6)	16.5 (15.4 to 17.7)
Week 20	16.3 (15.2 to 17.4)	17.3 (16.1 to 18.4)
Week 24	16.9 (15.7 to 18.1)	17.5 (16.3 to 18.6)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline in the Study Eye at Week 24

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End point title

Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline in the Study Eye at Week 24

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)	56.1 (50.4 to 61.9)	60.4 (54.7 to 66.0)

Gaining ≥15 Letters

Comparison groups

Arm A: Faricimab Q4W (Part 1) v Arm B: Aflibercept Q4W (Part 1)

Number of subjects included in analysis

553

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-4.3

Confidence interval

level

95%

sides

2-sided

lower limit

-12.3

upper limit

3.8

Secondary: Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	34.3 (28.9 to 39.8)	36.9 (31.5 to 42.3)
Week 8	41.2 (35.6 to 46.9)	46.7 (41.0 to 52.3)
Week 12	51.0 (45.3 to 56.7)	52.1 (46.3 to 57.8)
Week 16	53.6 (47.8 to 59.3)	56.4 (50.8 to 62.1)
Week 20	56.1 (50.3 to 61.8)	58.9 (53.3 to 64.6)
Week 24	56.1 (50.4 to 61.9)	60.4 (54.7 to 66.0)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants Gaining ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Percentage of Participants Gaining ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	57.5 (51.8 to 63.3)	59.2 (53.6 to 64.9)
Week 8	69.1 (63.8 to 74.5)	69.0 (63.6 to 74.4)
Week 12	75.0 (69.9 to 80.1)	74.8 (69.7 to 79.8)
Week 16	72.1 (66.9 to 77.3)	76.6 (71.6 to 81.5)
Week 20	75.3 (70.3 to 80.4)	79.1 (74.3 to 83.9)
Week 24	77.5 (72.6 to 82.4)	77.3 (72.4 to 82.2)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants Gaining ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Percentage of Participants Gaining ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	75.7 (70.7 to 80.7)	79.1 (74.4 to 83.9)
Week 8	84.0 (79.7 to 88.3)	88.1 (84.3 to 91.9)
Week 12	87.0 (83.1 to 90.9)	87.0 (83.1 to 91.0)
Week 16	85.9 (81.8 to 89.9)	88.8 (85.1 to 92.5)
Week 20	88.4 (84.6 to 92.2)	90.3 (86.8 to 93.7)
Week 24	90.9 (87.6 to 94.3)	89.6 (86.0 to 93.1)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants Gaining >0 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Percentage of Participants Gaining >0 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	90.2 (86.8 to 93.6)	93.2 (90.3 to 96.1)
Week 8	92.7 (89.7 to 95.8)	96.8 (94.7 to 98.8)
Week 12	94.9 (92.4 to 97.5)	94.2 (91.5 to 97.0)
Week 16	93.8 (91.1 to 96.6)	94.9 (92.4 to 97.5)
Week 20	94.9 (92.4 to 97.5)	96.0 (93.8 to 98.3)
Week 24	96.4 (94.2 to 98.6)	95.3 (92.9 to 97.8)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	99.3 (98.3 to 100.0)	98.9 (97.7 to 100.0)
Week 8	99.3 (98.3 to 100.0)	98.9 (97.7 to 100.0)
Week 12	99.3 (98.3 to 100.0)	98.9 (97.7 to 100.0)
Week 16	99.3 (98.3 to 100.0)	98.6 (97.2 to 99.9)
Week 20	99.6 (98.9 to 100.0)	98.6 (97.2 to 99.9)
Week 24	99.6 (98.9 to 100.0)	98.6 (97.2 to 99.9)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	98.5 (97.1 to 99.9)	98.9 (97.7 to 100.0)
Week 8	98.5 (97.1 to 100.0)	98.9 (97.7 to 100.0)
Week 12	98.5 (97.1 to 99.9)	98.9 (97.7 to 100.0)
Week 16	98.5 (97.1 to 99.9)	98.2 (96.7 to 99.7)
Week 20	99.3 (98.3 to 100.0)	98.6 (97.2 to 99.9)
Week 24	99.6 (98.9 to 100.0)	98.2 (96.7 to 99.7)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	97.1 (95.1 to 99.1)	98.6 (97.2 to 99.9)
Week 8	97.8 (96.1 to 99.5)	98.6 (97.2 to 99.9)
Week 12	97.8 (96.1 to 99.5)	98.9 (97.7 to 100.0)
Week 16	97.8 (96.1 to 99.5)	98.2 (96.7 to 99.7)
Week 20	98.5 (97.1 to 99.9)	97.8 (96.2 to 99.5)
Week 24	98.6 (97.2 to 100.0)	97.5 (95.7 to 99.3)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants Achieving ≥84 Letters in BCVA (20/20 Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Percentage of Participants Achieving ≥84 Letters in BCVA (20/20 Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	8.7 (5.5 to 11.9)	8.6 (5.5 to 11.8)
Week 8	14.1 (10.3 to 18.0)	15.5 (11.5 to 19.5)
Week 12	15.6 (11.7 to 19.6)	20.2 (15.7 to 24.6)
Week 16	17.4 (13.3 to 21.6)	22.0 (17.4 to 26.5)
Week 20	20.7 (16.2 to 25.2)	23.8 (19.0 to 28.5)
Week 24	22.9 (18.2 to 27.6)	23.8 (19.1 to 28.5)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants Achieving ≥69 Letters in BCVA (20/40 or Better Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Percentage of Participants Achieving ≥69 Letters in BCVA (20/40 or Better Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	55.6 (50.6 to 60.5)	62.3 (57.3 to 67.3)
Week 8	63.9 (59.3 to 68.6)	70.3 (65.7 to 74.9)
Week 12	69.0 (64.4 to 73.6)	69.2 (64.4 to 74.0)
Week 16	72.2 (67.7 to 76.8)	72.1 (67.5 to 76.8)
Week 20	73.3 (69.1 to 77.6)	76.1 (71.7 to 80.5)
Week 24	73.7 (69.3 to 78.1)	76.5 (71.9 to 81.0)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants with ≤38 Letters in BCVA (20/200 or Worse Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Percentage of Participants with ≤38 Letters in BCVA (20/200 or Worse Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (>38 and ≤38 letters) and region (U.S. and Canada, Asia, and rest of the world). All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	3.6 (2.0 to 5.3)	1.5 (0.1 to 2.9)
Week 8	3.2 (1.3 to 5.0)	1.9 (0.5 to 3.3)
Week 12	2.3 (0.8 to 3.8)	1.5 (0.2 to 2.8)
Week 16	2.3 (0.8 to 3.8)	1.9 (0.4 to 3.3)
Week 20	2.3 (0.8 to 3.8)	1.9 (0.4 to 3.3)
Week 24	2.3 (0.8 to 3.8)	1.9 (0.4 to 3.3)

No statistical analyses for this end point

Secondary: Part 1: Change from Baseline in Central Subfield Thickness in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Change from Baseline in Central Subfield Thickness in the Study Eye at Specified Timepoints Through Week 24

End point description

Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline CST (continuous), and randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: microns
arithmetic mean (confidence interval 95%)
Week 4	-283.9 (-290.1 to -277.8)	-281.1 (-287.2 to -274.9)
Week 8	-299.4 (-305.2 to -293.7)	-296.9 (-302.6 to -291.2)
Week 12	-304.4 (-309.7 to -299.1)	-298.8 (-304.1 to -293.5)
Week 16	-306.1 (-311.5 to -300.8)	-301.4 (-306.7 to -296.1)
Week 20	-307.3 (-312.5 to -302.1)	-302.2 (-307.4 to -297.0)
Week 24	-311.4 (-316.4 to -306.4)	-304.4 (-309.3 to -299.4)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants with Absence of Macular Edema in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Percentage of Participants with Absence of Macular Edema in the Study Eye at Specified Timepoints Through Week 24

End point description

Absence of diabetic macular edema was defined as achieving a central subfield thickness of <325 microns in the study eye. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	88.8 (85.1 to 92.5)	88.1 (84.4 to 91.9)
Week 8	94.5 (91.9 to 97.2)	93.2 (90.3 to 96.1)
Week 12	96.4 (94.2 to 98.5)	92.1 (89.0 to 95.2)
Week 16	95.3 (92.8 to 97.7)	93.6 (90.7 to 96.4)
Week 20	96.0 (93.7 to 98.3)	94.6 (92.1 to 97.2)
Week 24	95.3 (92.8 to 97.7)	93.9 (91.2 to 96.6)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants with Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Percentage of Participants with Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 24

End point description

Intraretinal fluid was measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	46.1 (40.2 to 51.9)	54.8 (49.0 to 60.6)
Week 8	53.8 (48.2 to 59.4)	57.4 (51.6 to 63.1)
Week 12	65.3 (59.7 to 70.8)	56.6 (50.8 to 62.4)
Week 16	69.9 (64.6 to 75.3)	72.9 (67.8 to 78.1)
Week 20	67.1 (61.6 to 72.6)	66.4 (60.9 to 71.9)
Week 24	72.5 (67.3 to 77.7)	66.0 (60.5 to 71.6)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants with Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Percentage of Participants with Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24

End point description

Subretinal fluid was measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	76.1 (71.1 to 81.1)	72.9 (67.8 to 78.1)
Week 8	93.1 (90.2 to 96.1)	91.4 (88.1 to 94.6)
Week 12	96.4 (94.2 to 98.6)	97.1 (95.2 to 99.1)
Week 16	95.3 (92.8 to 97.8)	96.4 (94.2 to 98.6)
Week 20	98.2 (96.6 to 99.8)	97.8 (96.1 to 99.5)
Week 24	91.3 (88.0 to 94.6)	90.3 (86.9 to 93.7)

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants with Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24

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End point title

Part 1: Percentage of Participants with Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24

End point description

Intraretinal fluid and subretinal fluid were measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, and 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	37.8 (32.1 to 43.4)	40.8 (35.2 to 46.4)
Week 8	50.9 (45.3 to 56.5)	54.1 (48.4 to 59.9)
Week 12	63.8 (58.2 to 69.4)	56.3 (50.5 to 62.1)
Week 16	67.1 (61.6 to 72.6)	72.6 (67.4 to 77.8)
Week 20	66.0 (60.5 to 71.5)	66.0 (60.5 to 71.6)
Week 24	66.3 (60.8 to 71.9)	61.0 (55.3 to 66.7)

No statistical analyses for this end point

Secondary: Part 1: Change from Baseline in National Eye Institute 25-Item Visual Functioning Questionnaire (NEI VFQ-25) Composite Score at Week 24

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End point title

Part 1: Change from Baseline in National Eye Institute 25-Item Visual Functioning Questionnaire (NEI VFQ-25) Composite Score at Week 24

End point description

The NEI VFQ-25 captures a patient’s perception of vision-related functioning and vision-related quality of life. The core measure includes 25 items that comprise 11 vision-related subscales and 1 item on general health. The composite score ranges from 0 to 100, with higher scores indicating better vision-related functioning. For the ANCOVA analysis, the model uses the non-missing change from baseline in BCVA at Weeks 24 as the response variables adjusted for the treatment group, baseline NEI VFQ-25 Composite Score (continuous), baseline BCVA score (≥55 and ≤54 letters) and region (U.S. and Canada, Asia, and the rest of the world). Observed NEI VFQ-25 assessments were used regardless of the occurrence of intercurrent events. Missing data were not imputed. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)
Number of subjects analysed	253	244
Units: score on a scale
arithmetic mean (confidence interval 95%)	5.6 (4.5 to 6.7)	5.9 (4.8 to 7.1)

NEI VFQ-25 at Week 24

Comparison groups

Arm A: Faricimab Q4W (Part 1) v Arm B: Aflibercept Q4W (Part 1)

Number of subjects included in analysis

497

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in Adjusted Means

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.76

Secondary: Parts 1 and 2: Change from Baseline in BCVA in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Change from Baseline in BCVA in the Study Eye at Specified Timepoints Through Week 72

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: ETDRS Letters
arithmetic mean (confidence interval 95%)
Week 4	11.5 (10.5 to 12.5)	12.4 (11.4 to 13.4)
Week 8	13.7 (12.6 to 14.7)	15.1 (14.1 to 16.2)
Week 12	15.1 (14.0 to 16.1)	15.9 (14.8 to 17.0)
Week 16	15.5 (14.4 to 16.6)	16.5 (15.4 to 17.6)
Week 20	16.3 (15.1 to 17.4)	17.2 (16.1 to 18.4)
Week 24	16.8 (15.6 to 17.9)	17.5 (16.3 to 18.6)
Week 28	16.5 (15.3 to 17.6)	17.3 (16.2 to 18.4)
Week 32	17.2 (16.0 to 18.4)	17.5 (16.3 to 18.7)
Week 36	17.3 (16.1 to 18.4)	18.0 (16.8 to 19.2)
Week 40	17.3 (16.1 to 18.4)	17.7 (16.6 to 18.9)
Week 44	18.1 (16.8 to 19.3)	17.7 (16.5 to 18.9)
Week 48	18.0 (16.8 to 19.3)	18.2 (17.0 to 19.4)
Week 52	18.0 (16.7 to 19.3)	18.4 (17.1 to 19.7)
Week 56	17.3 (16.0 to 18.6)	18.1 (16.8 to 19.4)
Week 60	18.0 (16.7 to 19.3)	18.6 (17.3 to 19.8)
Week 64	17.9 (16.6 to 19.2)	18.6 (17.3 to 19.9)
Week 68	18.1 (16.8 to 19.4)	18.8 (17.5 to 20.1)
Week 72	18.4 (17.1 to 19.7)	18.8 (17.5 to 20.1)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	34.3 (28.9 to 39.8)	36.9 (31.5 to 42.3)
Week 8	41.2 (35.6 to 46.9)	46.7 (41.0 to 52.3)
Week 12	51.0 (45.3 to 56.7)	52.1 (46.3 to 57.8)
Week 16	53.6 (47.8 to 59.3)	56.4 (50.8 to 62.1)
Week 20	56.1 (50.3 to 61.8)	58.9 (53.3 to 64.6)
Week 24	56.1 (50.4 to 61.9)	60.4 (54.7 to 66.0)
Week 28	55.8 (50.0 to 61.5)	61.8 (56.2 to 67.4)
Week 32	59.0 (53.3 to 64.6)	61.4 (55.8 to 67.1)
Week 36	61.2 (55.5 to 66.8)	62.5 (56.9 to 68.1)
Week 40	60.8 (55.2 to 66.4)	61.1 (55.4 to 66.7)
Week 44	65.5 (60.1 to 71.0)	58.9 (53.4 to 64.5)
Week 48	64.1 (58.5 to 69.6)	60.7 (55.1 to 66.3)
Week 52	61.2 (55.6 to 66.8)	64.0 (58.4 to 69.5)
Week 56	57.9 (52.3 to 63.5)	63.6 (58.1 to 69.2)
Week 60	62.6 (57.1 to 68.1)	62.9 (57.4 to 68.4)
Week 64	61.9 (56.3 to 67.4)	65.4 (59.9 to 70.9)
Week 68	63.0 (57.5 to 68.4)	64.7 (59.2 to 70.2)
Week 72	62.3 (56.7 to 67.8)	66.9 (61.5 to 72.3)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Percentage of Participants Gaining ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Percentage of Participants Gaining ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	57.5 (51.8 to 63.3)	59.2 (53.6 to 64.9)
Week 8	69.1 (63.8 to 74.5)	69.0 (63.6 to 74.4)
Week 12	75.0 (69.9 to 80.1)	74.8 (69.7 to 79.8)
Week 16	72.1 (66.9 to 77.3)	76.6 (71.6 to 81.5)
Week 20	75.3 (70.3 to 80.4)	79.1 (74.3 to 83.9)
Week 24	77.5 (72.6 to 82.4)	77.3 (72.4 to 82.2)
Week 28	76.1 (71.1 to 81.1)	76.6 (71.6 to 81.5)
Week 32	77.5 (72.6 to 82.4)	78.4 (73.6 to 83.2)
Week 36	75.7 (70.7 to 80.7)	78.7 (74.0 to 83.5)
Week 40	77.5 (72.7 to 82.4)	76.2 (71.3 to 81.2)
Week 44	80.4 (75.8 to 85.1)	76.6 (71.7 to 81.5)
Week 48	79.7 (75.0 to 84.4)	79.4 (74.7 to 84.2)
Week 52	80.8 (76.2 to 85.4)	80.2 (75.5 to 84.8)
Week 56	75.7 (70.7 to 80.7)	78.0 (73.2 to 82.9)
Week 60	79.3 (74.6 to 84.0)	80.5 (75.9 to 85.2)
Week 64	78.9 (74.2 to 83.7)	78.7 (73.9 to 83.5)
Week 68	78.9 (74.2 to 83.7)	77.3 (72.4 to 82.2)
Week 72	80.4 (75.8 to 85.0)	79.5 (74.7 to 84.2)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Percentage of Participants Gaining ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Percentage of Participants Gaining ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	75.7 (70.7 to 80.7)	79.1 (74.4 to 83.9)
Week 8	84.0 (79.7 to 88.3)	88.1 (84.3 to 91.9)
Week 12	87.0 (83.1 to 90.9)	87.0 (83.1 to 91.0)
Week 16	85.9 (81.8 to 89.9)	88.8 (85.1 to 92.5)
Week 20	88.4 (84.6 to 92.2)	90.3 (86.8 to 93.7)
Week 24	90.9 (87.6 to 94.3)	89.6 (86.0 to 93.1)
Week 28	89.1 (85.5 to 92.8)	87.8 (84.0 to 91.6)
Week 32	89.5 (85.9 to 93.1)	87.7 (83.9 to 91.6)
Week 36	88.4 (84.6 to 92.1)	90.6 (87.2 to 94.0)
Week 40	90.2 (86.7 to 93.7)	90.6 (87.2 to 94.0)
Week 44	89.1 (85.5 to 92.8)	88.4 (84.7 to 92.2)
Week 48	88.4 (84.6 to 92.2)	90.3 (86.8 to 93.8)
Week 52	89.9 (86.4 to 93.4)	88.5 (84.7 to 92.2)
Week 56	88.0 (84.3 to 91.8)	87.0 (83.1 to 91.0)
Week 60	89.9 (86.3 to 93.4)	88.1 (84.3 to 91.9)
Week 64	90.6 (87.1 to 94.0)	87.7 (83.9 to 91.6)
Week 68	89.5 (85.9 to 93.1)	87.1 (83.1 to 91.0)
Week 72	89.8 (86.3 to 93.4)	87.4 (83.5 to 91.3)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Percentage of Participants Gaining >0 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Percentage of Participants Gaining >0 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	90.2 (86.8 to 93.6)	93.2 (90.3 to 96.1)
Week 8	92.7 (89.7 to 95.8)	96.8 (94.7 to 98.8)
Week 12	94.9 (92.4 to 97.5)	94.2 (91.5 to 97.0)
Week 16	93.8 (91.1 to 96.6)	94.9 (92.4 to 97.5)
Week 20	94.9 (92.4 to 97.5)	96.0 (93.8 to 98.3)
Week 24	96.4 (94.2 to 98.6)	95.3 (92.9 to 97.8)
Week 28	95.3 (92.9 to 97.8)	95.0 (92.4 to 97.5)
Week 32	96.0 (93.8 to 98.3)	95.0 (92.4 to 97.5)
Week 36	94.2 (91.5 to 96.9)	94.6 (92.0 to 97.2)
Week 40	94.6 (91.9 to 97.2)	95.7 (93.3 to 98.0)
Week 44	95.3 (92.9 to 97.7)	94.6 (92.0 to 97.2)
Week 48	94.6 (92.0 to 97.2)	96.1 (93.8 to 98.3)
Week 52	93.8 (91.1 to 96.6)	94.6 (92.1 to 97.2)
Week 56	93.1 (90.2 to 96.1)	95.3 (92.9 to 97.8)
Week 60	94.6 (91.9 to 97.2)	94.2 (91.5 to 97.0)
Week 64	94.9 (92.4 to 97.5)	94.2 (91.5 to 97.0)
Week 68	93.5 (90.6 to 96.4)	93.9 (91.1 to 96.7)
Week 72	94.6 (91.9 to 97.2)	93.9 (91.1 to 96.7)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	99.3 (98.3 to 100.0)	98.9 (97.7 to 100.0)
Week 8	99.3 (98.3 to 100.0)	98.9 (97.7 to 100.0)
Week 12	99.3 (98.3 to 100.0)	98.9 (97.7 to 100.0)
Week 16	99.3 (98.3 to 100.0)	98.6 (97.2 to 99.9)
Week 20	99.6 (98.9 to 100.0)	98.6 (97.2 to 99.9)
Week 24	99.6 (98.9 to 100.0)	98.6 (97.2 to 99.9)
Week 28	99.6 (98.9 to 100.0)	98.6 (97.2 to 99.9)
Week 32	99.6 (98.9 to 100.0)	98.6 (97.2 to 99.9)
Week 36	99.6 (98.9 to 100.0)	98.6 (97.2 to 100.0)
Week 40	98.9 (97.7 to 100.0)	98.6 (97.2 to 100.0)
Week 44	99.3 (98.3 to 100.0)	98.6 (97.2 to 100.0)
Week 48	99.3 (98.3 to 100.0)	98.2 (96.7 to 99.8)
Week 52	98.6 (97.2 to 100.0)	98.2 (96.7 to 99.8)
Week 56	98.9 (97.7 to 100.0)	98.2 (96.7 to 99.8)
Week 60	99.3 (98.3 to 100.0)	98.2 (96.7 to 99.8)
Week 64	98.9 (97.7 to 100.0)	97.9 (96.2 to 99.5)
Week 68	98.9 (97.7 to 100.0)	98.2 (96.7 to 99.8)
Week 72	98.9 (97.7 to 100.0)	98.2 (96.7 to 99.8)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	98.5 (97.1 to 99.9)	98.9 (97.7 to 100.0)
Week 8	98.5 (97.1 to 100.0)	98.9 (97.7 to 100.0)
Week 12	98.5 (97.1 to 99.9)	98.9 (97.7 to 100.0)
Week 16	98.5 (97.1 to 99.9)	98.2 (96.7 to 99.7)
Week 20	99.3 (98.3 to 100.0)	98.6 (97.2 to 99.9)
Week 24	99.6 (98.9 to 100.0)	98.2 (96.7 to 99.7)
Week 28	99.6 (98.9 to 100.0)	98.2 (96.7 to 99.7)
Week 32	99.3 (98.3 to 100.0)	98.2 (96.7 to 99.7)
Week 36	99.6 (98.9 to 100.0)	98.6 (97.2 to 100.0)
Week 40	98.9 (97.7 to 100.0)	98.6 (97.2 to 100.0)
Week 44	99.3 (98.3 to 100.0)	98.2 (96.7 to 99.8)
Week 48	98.9 (97.7 to 100.0)	98.2 (96.7 to 99.8)
Week 52	98.6 (97.2 to 100.0)	98.2 (96.7 to 99.8)
Week 56	98.9 (97.7 to 100.0)	97.9 (96.2 to 99.5)
Week 60	98.9 (97.7 to 100.0)	98.2 (96.7 to 99.8)
Week 64	98.6 (97.2 to 99.9)	97.1 (95.2 to 99.1)
Week 68	98.6 (97.2 to 100.0)	97.9 (96.2 to 99.5)
Week 72	98.2 (96.6 to 99.8)	97.9 (96.2 to 99.5)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	97.1 (95.1 to 99.1)	98.6 (97.2 to 99.9)
Week 8	97.8 (96.1 to 99.5)	98.6 (97.2 to 99.9)
Week 12	97.8 (96.1 to 99.5)	98.9 (97.7 to 100.0)
Week 16	97.8 (96.1 to 99.5)	98.2 (96.7 to 99.7)
Week 20	98.5 (97.1 to 99.9)	97.8 (96.2 to 99.5)
Week 24	98.6 (97.2 to 100.0)	97.5 (95.7 to 99.3)
Week 28	98.2 (96.6 to 99.8)	97.5 (95.7 to 99.3)
Week 32	98.6 (97.2 to 99.9)	97.8 (96.2 to 99.5)
Week 36	98.2 (96.7 to 99.7)	97.5 (95.7 to 99.3)
Week 40	97.1 (95.2 to 99.0)	97.5 (95.6 to 99.3)
Week 44	98.6 (97.2 to 99.9)	97.8 (96.1 to 99.5)
Week 48	97.1 (95.2 to 99.0)	97.9 (96.2 to 99.5)
Week 52	97.1 (95.2 to 99.1)	97.5 (95.7 to 99.3)
Week 56	97.5 (95.6 to 99.3)	97.5 (95.7 to 99.3)
Week 60	97.8 (96.1 to 99.5)	96.8 (94.7 to 98.8)
Week 64	97.1 (95.1 to 99.1)	96.8 (94.7 to 98.8)
Week 68	97.1 (95.1 to 99.1)	97.1 (95.2 to 99.1)
Week 72	97.1 (95.1 to 99.1)	96.8 (94.7 to 98.8)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Percentage of Participants Achieving ≥84 Letters in BCVA (20/20 Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Percentage of Participants Achieving ≥84 Letters in BCVA (20/20 Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	8.7 (5.5 to 11.9)	8.6 (5.5 to 11.8)
Week 8	14.1 (10.3 to 18.0)	15.5 (11.5 to 19.5)
Week 12	15.6 (11.7 to 19.6)	20.2 (15.7 to 24.6)
Week 16	17.4 (13.3 to 21.6)	22.0 (17.4 to 26.5)
Week 20	20.7 (16.2 to 25.2)	23.8 (19.0 to 28.5)
Week 24	22.9 (18.2 to 27.6)	23.8 (19.1 to 28.5)
Week 28	24.0 (19.2 to 28.8)	25.6 (20.7 to 30.4)
Week 32	25.1 (20.3 to 29.8)	23.4 (18.8 to 28.0)
Week 36	25.1 (20.2 to 29.9)	25.2 (20.4 to 30.0)
Week 40	26.9 (22.0 to 31.8)	22.0 (17.4 to 26.5)
Week 44	26.8 (21.8 to 31.8)	24.8 (20.0 to 29.7)
Week 48	29.0 (24.0 to 34.1)	25.2 (20.3 to 30.1)
Week 52	26.8 (21.9 to 31.7)	25.6 (20.7 to 30.4)
Week 56	26.1 (21.2 to 31.0)	22.0 (17.3 to 26.6)
Week 60	27.6 (22.6 to 32.6)	25.6 (20.8 to 30.4)
Week 64	30.1 (25.0 to 35.3)	24.5 (19.7 to 29.3)
Week 68	29.4 (24.2 to 34.6)	25.9 (21.0 to 30.8)
Week 72	29.4 (24.3 to 34.5)	24.8 (20.0 to 29.7)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Percentage of Participants Achieving ≥69 Letters in BCVA (20/40 or Better Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Percentage of Participants Achieving ≥69 Letters in BCVA (20/40 or Better Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	55.6 (50.6 to 60.5)	62.3 (57.3 to 67.3)
Week 8	63.9 (59.3 to 68.6)	70.3 (65.7 to 74.9)
Week 12	69.0 (64.4 to 73.6)	69.2 (64.4 to 74.0)
Week 16	72.2 (67.7 to 76.8)	72.1 (67.5 to 76.8)
Week 20	73.3 (69.1 to 77.6)	76.1 (71.7 to 80.5)
Week 24	73.7 (69.3 to 78.1)	76.5 (71.9 to 81.0)
Week 28	73.3 (68.7 to 77.9)	75.4 (70.7 to 80.0)
Week 32	76.9 (72.6 to 81.2)	75.4 (70.7 to 80.1)
Week 36	76.2 (71.8 to 80.6)	77.9 (73.3 to 82.5)
Week 40	75.5 (71.0 to 79.9)	76.8 (72.3 to 81.3)
Week 44	76.9 (72.4 to 81.4)	76.1 (71.4 to 80.7)
Week 48	77.2 (72.7 to 81.8)	79.3 (75.0 to 83.7)
Week 52	78.7 (74.3 to 83.1)	80.4 (76.1 to 84.7)
Week 56	76.2 (71.5 to 80.9)	79.0 (74.5 to 83.5)
Week 60	80.2 (75.8 to 84.5)	79.0 (74.5 to 83.5)
Week 64	77.6 (73.0 to 82.2)	81.1 (76.8 to 85.5)
Week 68	77.6 (73.0 to 82.2)	80.4 (76.0 to 84.9)
Week 72	78.0 (73.5 to 82.4)	79.0 (74.4 to 83.6)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Percentage of Participants with ≤38 Letters in BCVA (20/200 or Worse Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Percentage of Participants with ≤38 Letters in BCVA (20/200 or Worse Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (>38 and ≤38 letters) and region (U.S. and Canada, Asia, and rest of the world). All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	3.6 (2.0 to 5.3)	1.5 (0.1 to 2.9)
Week 8	3.2 (1.3 to 5.0)	1.9 (0.5 to 3.3)
Week 12	2.3 (0.8 to 3.8)	1.5 (0.2 to 2.8)
Week 16	2.3 (0.8 to 3.8)	1.9 (0.4 to 3.3)
Week 20	2.3 (0.8 to 3.8)	1.9 (0.4 to 3.3)
Week 24	2.3 (0.8 to 3.8)	1.9 (0.4 to 3.3)
Week 28	2.0 (0.6 to 3.5)	1.9 (0.4 to 3.3)
Week 32	2.4 (0.8 to 4.0)	1.9 (0.4 to 3.3)
Week 36	1.9 (0.5 to 3.4)	1.5 (0.2 to 2.8)
Week 40	2.3 (0.8 to 3.7)	1.5 (0.2 to 2.8)
Week 44	2.7 (1.0 to 4.4)	1.5 (0.2 to 2.8)
Week 48	2.4 (0.8 to 4.0)	2.2 (0.6 to 3.9)
Week 52	3.1 (1.3 to 4.9)	2.6 (0.9 to 4.3)
Week 56	2.7 (1.0 to 4.4)	2.6 (0.9 to 4.3)
Week 60	2.1 (0.6 to 3.6)	2.6 (0.9 to 4.3)
Week 64	3.1 (1.3 to 4.9)	2.2 (0.6 to 3.9)
Week 68	2.1 (0.6 to 3.6)	1.8 (0.3 to 3.3)
Week 72	2.1 (0.6 to 3.6)	2.2 (0.5 to 3.9)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Change from Baseline in NEI VFQ-25 Questionnaire Composite Score at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Change from Baseline in NEI VFQ-25 Questionnaire Composite Score at Specified Timepoints Through Week 72

End point description

The NEI VFQ-25 captures a patient’s perception of vision-related functioning and vision-related quality of life. The core measure includes 25 items that comprise 11 vision-related subscales and 1 item on general health. The composite score ranges from 0 to 100, with higher scores indicating better vision-related functioning. For the MMRM analysis, the model adjusted for the treatment group, visit, visit-by-treatment group interaction, baseline NEI VFQ-25 Composite Score continuous), baseline BCVA score (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and the rest of the world). Observed NEI VFQ-25 assessments were used regardless of the occurrence of intercurrent events. Missing data were implicitly imputed. Invalid BCVA values were excluded. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Baseline and Weeks 24, 48, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: score on a scale
arithmetic mean (confidence interval 95%)
Week 24	5.6 (4.5 to 6.6)	5.9 (4.9 to 7.0)
Week 48	6.4 (5.3 to 7.5)	6.3 (5.2 to 7.4)
Week 72	6.0 (4.8 to 7.3)	7.8 (6.6 to 9.0)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Change from Baseline in Central Subfield Thickness in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Change from Baseline in Central Subfield Thickness in the Study Eye at Specified Timepoints Through Week 72

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: microns
arithmetic mean (confidence interval 95%)
Week 4	-287.3 (-293.5 to -281.1)	-284.3 (-290.4 to -278.2)
Week 8	-302.9 (-308.7 to -297.2)	-300.2 (-306.0 to -294.5)
Week 12	-307.8 (-313.1 to -302.6)	-301.9 (-307.1 to -296.7)
Week 16	-309.3 (-314.6 to -304.0)	-304.5 (-309.8 to -299.3)
Week 20	-310.6 (-315.5 to -305.6)	-304.2 (-309.1 to -299.3)
Week 24	-314.5 (-319.5 to -309.6)	-307.6 (-312.5 to -302.7)
Week 28	-294.0 (-302.2 to -285.8)	-285.1 (-293.3 to -276.9)
Week 32	-308.3 (-314.6 to -302.0)	-303.2 (-309.4 to -297.0)
Week 36	-304.1 (-310.6 to -297.6)	-298.8 (-305.2 to -292.4)
Week 40	-296.7 (-304.4 to -288.9)	-285.8 (-293.7 to -278.0)
Week 44	-309.2 (-315.9 to -302.5)	-301.6 (-308.3 to -294.9)
Week 48	-309.4 (-315.3 to -303.5)	-302.8 (-308.7 to -296.9)
Week 52	-302.2 (-308.6 to -295.7)	-302.4 (-308.8 to -296.0)
Week 56	-294.0 (-302.6 to -285.5)	-288.0 (-296.6 to -279.4)
Week 60	-309.5 (-315.1 to -303.9)	-306.2 (-311.9 to -300.6)
Week 64	-311.1 (-316.3 to -305.9)	-305.9 (-311.1 to -300.7)
Week 68	-311.2 (-316.3 to -306.1)	-307.9 (-313.0 to -302.8)
Week 72	-310.5 (-315.7 to -305.4)	-307.2 (-312.3 to -302.0)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Percentage of Participants with Absence of Macular Edema in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Percentage of Participants with Absence of Macular Edema in the Study Eye at Specified Timepoints Through Week 72

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	88.8 (85.1 to 92.5)	88.1 (84.4 to 91.9)
Week 8	94.5 (91.9 to 97.2)	93.2 (90.3 to 96.1)
Week 12	96.4 (94.2 to 98.5)	92.1 (89.0 to 95.2)
Week 16	95.3 (92.8 to 97.7)	93.6 (90.7 to 96.4)
Week 20	96.0 (93.7 to 98.3)	94.6 (92.1 to 97.2)
Week 24	95.6 (93.3 to 98.0)	94.3 (91.6 to 96.9)
Week 28	89.1 (85.5 to 92.8)	86.0 (82.0 to 90.0)
Week 32	94.6 (91.9 to 97.2)	92.5 (89.4 to 95.5)
Week 36	93.8 (91.1 to 96.5)	90.7 (87.3 to 94.0)
Week 40	89.5 (85.9 to 93.0)	84.2 (79.9 to 88.4)
Week 44	96.0 (93.7 to 98.3)	92.1 (88.9 to 95.2)
Week 48	94.9 (92.4 to 97.5)	91.4 (88.1 to 94.6)
Week 52	92.4 (89.3 to 95.5)	91.4 (88.2 to 94.6)
Week 56	89.5 (85.9 to 93.1)	86.3 (82.3 to 90.3)
Week 60	94.2 (91.5 to 96.9)	93.9 (91.1 to 96.7)
Week 64	95.3 (92.8 to 97.8)	93.9 (91.1 to 96.7)
Week 68	94.9 (92.4 to 97.5)	92.4 (89.4 to 95.5)
Week 72	94.2 (91.5 to 96.9)	94.2 (91.5 to 97.0)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Percentage of Participants with Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Percentage of Participants with Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 72

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	46.1 (40.2 to 51.9)	54.8 (49.0 to 60.6)
Week 8	53.8 (48.2 to 59.4)	57.4 (51.6 to 63.1)
Week 12	65.3 (59.7 to 70.8)	56.6 (50.8 to 62.4)
Week 16	69.9 (64.6 to 75.3)	72.9 (67.8 to 78.1)
Week 20	67.1 (61.6 to 72.6)	66.4 (60.9 to 71.9)
Week 24	73.9 (68.9 to 79.0)	69.3 (63.9 to 74.7)
Week 28	54.4 (48.7 to 60.2)	47.6 (41.8 to 53.5)
Week 32	68.1 (62.6 to 73.6)	65.0 (59.4 to 70.6)
Week 36	60.9 (55.1 to 66.6)	56.0 (50.2 to 61.7)
Week 40	50.8 (45.0 to 56.6)	48.1 (42.3 to 53.9)
Week 44	70.3 (64.9 to 75.6)	63.9 (58.3 to 69.6)
Week 48	76.1 (71.1 to 81.1)	67.9 (62.5 to 73.3)
Week 52	55.8 (50.0 to 61.7)	56.7 (50.9 to 62.5)
Week 56	58.4 (52.6 to 64.1)	58.9 (53.2 to 64.6)
Week 60	75.0 (69.9 to 80.1)	72.6 (67.4 to 77.7)
Week 64	75.8 (70.9 to 80.7)	69.7 (64.3 to 75.1)
Week 68	69.9 (64.5 to 75.3)	68.6 (63.2 to 74.1)
Week 72	72.8 (67.6 to 78.0)	72.9 (67.7 to 78.1)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Percentage of Participants with Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Percentage of Participants with Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 72

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	76.1 (71.1 to 81.1)	72.9 (67.8 to 78.1)
Week 8	93.1 (90.2 to 96.1)	91.4 (88.1 to 94.6)
Week 12	96.4 (94.2 to 98.6)	97.1 (95.2 to 99.1)
Week 16	95.3 (92.8 to 97.8)	96.4 (94.2 to 98.6)
Week 20	98.2 (96.6 to 99.8)	97.8 (96.1 to 99.5)
Week 24	91.3 (88.0 to 94.6)	90.3 (86.9 to 93.7)
Week 28	93.5 (90.7 to 96.4)	91.0 (87.6 to 94.3)
Week 32	96.4 (94.2 to 98.6)	97.1 (95.2 to 99.1)
Week 36	97.1 (95.1 to 99.1)	96.0 (93.7 to 98.3)
Week 40	96.8 (94.7 to 98.8)	95.7 (93.3 to 98.1)
Week 44	97.5 (95.7 to 99.3)	95.7 (93.3 to 98.0)
Week 48	97.1 (95.1 to 99.1)	94.6 (91.9 to 97.2)
Week 52	98.2 (96.6 to 99.8)	97.1 (95.2 to 99.1)
Week 56	95.3 (92.8 to 97.8)	95.0 (92.4 to 97.5)
Week 60	95.7 (93.3 to 98.1)	96.0 (93.8 to 98.3)
Week 64	98.2 (96.7 to 99.7)	96.8 (94.7 to 98.8)
Week 68	97.5 (95.6 to 99.3)	97.5 (95.7 to 99.3)
Week 72	96.4 (94.2 to 98.6)	94.9 (92.4 to 97.5)

No statistical analyses for this end point

Secondary: Parts 1 and 2: Percentage of Participants with Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 72

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End point title

Parts 1 and 2: Percentage of Participants with Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 72

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 4	37.8 (32.1 to 43.4)	40.8 (35.2 to 46.4)
Week 8	50.9 (45.3 to 56.5)	54.1 (48.4 to 59.9)
Week 12	63.8 (58.2 to 69.4)	56.3 (50.5 to 62.1)
Week 16	67.1 (61.6 to 72.6)	72.6 (67.4 to 77.8)
Week 20	66.0 (60.5 to 71.5)	66.0 (60.5 to 71.6)
Week 24	67.4 (61.9 to 72.9)	64.3 (58.6 to 69.9)
Week 28	53.0 (47.2 to 58.7)	46.9 (41.1 to 52.8)
Week 32	67.4 (61.9 to 72.9)	64.6 (59.0 to 70.2)
Week 36	60.5 (54.8 to 66.3)	54.2 (48.4 to 59.9)
Week 40	50.4 (44.6 to 56.2)	47.3 (41.5 to 53.2)
Week 44	69.6 (64.2 to 74.9)	63.6 (57.9 to 69.2)
Week 48	74.7 (69.6 to 79.8)	65.4 (59.8 to 70.9)
Week 52	55.5 (49.6 to 61.3)	55.6 (49.8 to 61.4)
Week 56	58.0 (52.2 to 63.8)	57.8 (52.0 to 63.6)
Week 60	73.9 (68.8 to 79.1)	70.4 (65.1 to 75.7)
Week 64	75.4 (70.5 to 80.4)	69.3 (64.0 to 74.7)
Week 68	68.9 (63.4 to 74.3)	68.3 (62.8 to 73.7)
Week 72	70.7 (65.3 to 76.0)	71.1 (65.8 to 76.4)

No statistical analyses for this end point

Secondary: Part 2: Change from Week 24 in BCVA in the Study Eye at Specified Timepoints Through Week 72

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End point title

Part 2: Change from Week 24 in BCVA in the Study Eye at Specified Timepoints Through Week 72

End point description

End point type

Secondary

End point timeframe

Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W to Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: ETDRS Letters
arithmetic mean (confidence interval 95%)
Week 28	-0.3 (-0.8 to 0.3)	-0.1 (-0.6 to 0.5)
Week 32	0.5 (-0.1 to 1.0)	0.0 (-0.6 to 0.5)
Week 36	0.5 (-0.2 to 1.2)	0.6 (-0.1 to 1.2)
Week 40	0.3 (-0.4 to 1.1)	0.4 (-0.3 to 1.2)
Week 44	1.1 (0.3 to 1.9)	0.3 (-0.5 to 1.1)
Week 48	1.1 (0.3 to 2.0)	0.7 (-0.1 to 1.6)
Week 52	1.1 (0.2 to 2.0)	0.9 (0.0 to 1.8)
Week 56	0.4 (-0.5 to 1.4)	0.6 (-0.3 to 1.6)
Week 60	1.0 (0.1 to 2.0)	1.1 (0.1 to 2.0)
Week 64	0.9 (0.0 to 1.9)	1.2 (0.2 to 2.2)
Week 68	1.2 (0.2 to 2.1)	1.3 (0.4 to 2.2)
Week 72	1.5 (0.5 to 2.5)	1.3 (0.3 to 2.3)

No statistical analyses for this end point

Secondary: Part 2: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA from Week 24 in the Study Eye at Specified Timepoints Through Week 72

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End point title

Part 2: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA from Week 24 in the Study Eye at Specified Timepoints Through Week 72

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W to Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 28	85.5 (81.4 to 89.6)	84.1 (79.8 to 88.3)
Week 32	89.1 (85.5 to 92.7)	87.7 (83.9 to 91.5)
Week 36	89.5 (85.9 to 93.1)	88.4 (84.7 to 92.2)
Week 40	89.5 (85.9 to 93.0)	88.0 (84.2 to 91.8)
Week 44	89.9 (86.3 to 93.4)	86.3 (82.2 to 90.3)
Week 48	89.5 (85.9 to 93.1)	86.6 (82.6 to 90.6)
Week 52	89.9 (86.3 to 93.4)	87.7 (83.9 to 91.6)
Week 56	88.0 (84.3 to 91.8)	86.6 (82.6 to 90.6)
Week 60	88.8 (85.1 to 92.5)	87.0 (83.0 to 90.9)
Week 64	89.5 (85.9 to 93.1)	86.6 (82.6 to 90.6)
Week 68	88.4 (84.7 to 92.1)	87.0 (83.0 to 90.9)
Week 72	88.4 (84.7 to 92.1)	87.0 (83.0 to 90.9)

No statistical analyses for this end point

Secondary: Part 2: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA from Week 24 in the Study Eye at Specified Timepoints Through Week 72

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End point title

Part 2: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA from Week 24 in the Study Eye at Specified Timepoints Through Week 72

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W to Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 28	84.8 (80.6 to 89.0)	82.3 (77.8 to 86.7)
Week 32	88.8 (85.1 to 92.5)	85.9 (81.8 to 89.9)
Week 36	87.3 (83.4 to 91.2)	87.0 (83.0 to 90.9)
Week 40	87.7 (83.8 to 91.5)	86.3 (82.2 to 90.3)
Week 44	88.8 (85.1 to 92.5)	85.5 (81.4 to 89.7)
Week 48	88.4 (84.7 to 92.2)	85.2 (81.0 to 89.3)
Week 52	88.4 (84.7 to 92.2)	85.2 (81.0 to 89.3)
Week 56	86.2 (82.2 to 90.2)	83.4 (79.0 to 87.7)
Week 60	86.9 (83.0 to 90.9)	83.4 (79.0 to 87.7)
Week 64	86.9 (83.0 to 90.9)	85.2 (81.0 to 89.4)
Week 68	86.6 (82.6 to 90.6)	85.5 (81.4 to 89.7)
Week 72	86.6 (82.6 to 90.6)	85.5 (81.4 to 89.7)

No statistical analyses for this end point

Secondary: Part 2: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA from Week 24 in the Study Eye at Specified Timepoints Through Week 72

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End point title

Part 2: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA from Week 24 in the Study Eye at Specified Timepoints Through Week 72

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W to Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 28	74.6 (69.5 to 79.7)	73.6 (68.5 to 78.8)
Week 32	80.0 (75.4 to 84.7)	77.2 (72.3 to 82.1)
Week 36	79.7 (75.0 to 84.4)	79.0 (74.2 to 83.8)
Week 40	78.6 (73.8 to 83.4)	78.3 (73.5 to 83.1)
Week 44	83.3 (79.0 to 87.7)	76.9 (71.9 to 81.9)
Week 48	82.6 (78.2 to 87.0)	79.4 (74.6 to 84.1)
Week 52	81.5 (77.0 to 86.0)	79.4 (74.6 to 84.1)
Week 56	76.4 (71.5 to 81.3)	78.3 (73.5 to 83.1)
Week 60	79.0 (74.2 to 83.7)	77.2 (72.3 to 82.1)
Week 64	77.9 (73.0 to 82.8)	76.1 (71.1 to 81.1)
Week 68	78.2 (73.4 to 83.1)	76.5 (71.6 to 81.5)
Week 72	77.5 (72.7 to 82.4)	77.6 (72.7 to 82.5)

No statistical analyses for this end point

Secondary: Part 2: Percentage of Participants Avoiding a Loss of >0 Letters in BCVA from Week 24 in the Study Eye at Specified Timepoints Through Week 72

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End point title

Part 2: Percentage of Participants Avoiding a Loss of >0 Letters in BCVA from Week 24 in the Study Eye at Specified Timepoints Through Week 72

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors [baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.

End point type

Secondary

End point timeframe

Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

End point values	Arm A: Faricimab Q4W to Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)
Number of subjects analysed	276	277
Units: Percentage of participants
number (confidence interval 95%)
Week 28	46.4 (40.6 to 52.3)	51.3 (45.4 to 57.1)
Week 32	55.4 (49.6 to 61.2)	54.2 (48.3 to 60.0)
Week 36	55.1 (49.2 to 60.9)	52.7 (46.9 to 58.6)
Week 40	56.2 (50.4 to 62.0)	55.2 (49.4 to 61.1)
Week 44	62.4 (56.7 to 68.0)	56.0 (50.1 to 61.8)
Week 48	63.8 (58.2 to 69.4)	56.6 (50.9 to 62.4)
Week 52	59.8 (54.1 to 65.5)	58.5 (52.7 to 64.3)
Week 56	57.2 (51.5 to 63.0)	57.4 (51.5 to 63.2)
Week 60	58.0 (52.1 to 63.8)	60.3 (54.5 to 66.0)
Week 64	62.0 (56.3 to 67.7)	56.6 (50.8 to 62.5)
Week 68	60.9 (55.1 to 66.6)	58.8 (53.1 to 64.6)
Week 72	63.0 (57.4 to 68.7)	58.1 (52.3 to 63.9)

No statistical analyses for this end point

Secondary: Part 2: Percentage of Participants on Different Treatment Intervals at Week 68

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End point title

Part 2: Percentage of Participants on Different Treatment Intervals at Week 68

End point description

In Part 2 of the study, participants in both the faricimab Q4W and aflibercept Q4W arms in Part 1 received 6 mg faricimab intravitreal injections administered according to a personalized treatment interval (PTI) dosing regimen in intervals between Q4W and Q16W. At faricimab dosing visits, treatment intervals were maintained or adjusted (i.e., increased by 4 weeks or decreased by 4, 8, or 12 weeks), based on central subfield thickness (CST) and BCVA values.

End point type

Secondary

End point timeframe

Week 68

End point values	Arm A: Faricimab Q4W to Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)
Number of subjects analysed	248	244
Units: Percentage of participants
number (confidence interval 95%)
Once Every 4 Weeks (Q4W)	22.6 (17.4 to 27.8)	25.0 (19.6 to 30.4)
Once Every 8 Weeks (Q8W)	13.3 (9.1 to 17.5)	18.0 (13.2 to 22.9)
Once Every 12 Weeks (Q12W)	11.7 (7.7 to 15.7)	9.4 (5.8 to 13.1)
Once Every 16 Weeks (Q16W)	52.4 (46.2 to 58.6)	47.5 (41.3 to 53.8)

No statistical analyses for this end point

Secondary: Incidence and Severity of Ocular Adverse Events in the Study Eye, with Severity Determined According to Adverse Event Severity Grading Scale

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End point title

Incidence and Severity of Ocular Adverse Events in the Study Eye, with Severity Determined According to Adverse Event Severity Grading Scale

End point description

This analysis of adverse events (AEs) only includes ocular AEs that occurred in the study eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. Ocular AEs of special interest included the following: Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation (IOI).

End point type

Secondary

End point timeframe

Part 1: From first dose up to Week 24; Part 2: from Week 24 through Week 72

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)	Arm A: Faricimab Q4W to Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)
Number of subjects analysed	276	274	270	267
Units: Participants
Adverse Event (AE)	45	56	76	81
AE by Severity: Mild	40	47	50	64
AE by Severity: Moderate	4	8	25	16
AE by Severity: Severe	0	1	1	1
AE by Severity: Missing	1	0	0	0
Serious Adverse Event (SAE)	3	2	4	3
AE Leading to Withdrawal from Study Treatment	0	0	0	1
Treatment Related AEs	1	3	7	8
Treatment Related SAEs	0	0	0	0
Any AE of Special Interest (AESI)	1	2	1	1
AESI: Drop in Visual Acuity Score ≥30	1	2	1	1

No statistical analyses for this end point

Secondary: Part 2: Number of Study Drug Injections Received in the Study Eye from Week 24 Through Week 72

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End point title

Part 2: Number of Study Drug Injections Received in the Study Eye from Week 24 Through Week 72

End point description

Safety-Evaluable Population: All participants randomized in the study who received at least one injection of active study drug in the study eye. For Part 2, the safety analysis included: in Arm A, all participants with Week 24 treatment or dose hold, or if none, follow-up beyond Day 168; in Arm B, all participants who received at least one faricimab dose.

End point type

Secondary

End point timeframe

From Week 24 to Week 72

End point values	Arm A: Faricimab Q4W to Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)
Number of subjects analysed	270	267
Units: Injections
median (full range (min-max))	4.0 (1 to 12)	4.0 (1 to 12)

No statistical analyses for this end point

Secondary: Incidence of Non-Ocular Adverse Events

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End point title

Incidence of Non-Ocular Adverse Events

End point description

This analysis of adverse events (AEs) only includes non-ocular (systemic) AEs. Investigators sought information on adverse events (AEs) at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. The non-ocular AE of special interest was: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.

End point type

Secondary

End point timeframe

Part 1: From first dose up to Week 24; Part 2: from Week 24 through Week 72

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)	Arm A: Faricimab Q4W to Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)
Number of subjects analysed	276	274	270	267
Units: Participants
Adverse Event (AE)	94	99	136	126
Serious Adverse Event (SAE)	9	16	25	23
AE Leading to Withdrawal from Study Treatment	1	0	0	3
Any AE of Special Interest (AESI)	0	0	0	0

No statistical analyses for this end point

Secondary: Incidence of Ocular Adverse Events in the Fellow Eye

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End point title

Incidence of Ocular Adverse Events in the Fellow Eye

End point description

This analysis of adverse events (AEs) only includes ocular AEs that occurred in the fellow eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. Ocular AEs of special interest included the following: Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation (IOI).

End point type

Secondary

End point timeframe

Part 1: From first dose up to Week 24; Part 2: from Week 24 through Week 72

End point values	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)	Arm A: Faricimab Q4W to Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)
Number of subjects analysed	276	274	270	267
Units: Participants
Adverse Event (AE)	25	21	37	30
Serious Adverse Event (SAE)	0	0	0	0
Any AE of Special Interest (AESI)	0	0	0	0

No statistical analyses for this end point

Secondary: Plasma Concentration of Faricimab Over Time

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End point title

Plasma Concentration of Faricimab Over Time

End point description

Pharmacokinetic-Evaluable Population: All safety- evaluable participants randomized to faricimab arm or who received faricimab with at least one plasma sample, provided sufficient dosing information (dose and dosing time) is available. The number analyzed indicates all participants who provided a PK sample at a given timepoint. The values '999999' indicate that 0 participants provided samples at that timepoint, and therefore, there were no results to report.

End point type

Secondary

End point timeframe

Predose at Day 1 (Baseline), Weeks 4, 24, 28, 52, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
Number of subjects analysed	276	268
Units: microgram per millilitre (μg/mL)
arithmetic mean (standard deviation)
Baseline (n = 273, 0)	0.0000 ( 0.0000 )	999999 ( 999999 )
Week 4 (n = 264, 0)	0.0215 ( 0.0160 )	999999 ( 999999 )
Week 24 (n = 247, 241)	0.0220 ( 0.0181 )	0.0005 ( 0.0006 )
Week 28 (n = 238, 242)	0.0040 ( 0.0072 )	0.0025 ( 0.077 )
Week 52 (n = 231, 224)	0.0061 ( 0.0110 )	0.0097 ( 0.0156 )
Week 72 (n = 231, 229)	0.0076 ( 0.0109 )	0.0087 ( 0.0146 )

No statistical analyses for this end point

Secondary: Number of Participants with Anti-Drug Antibodies (ADAs) to Faricimab at Baseline and Post-Baseline During the Study

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End point title

Number of Participants with Anti-Drug Antibodies (ADAs) to Faricimab at Baseline and Post-Baseline During the Study

End point description

Anti-drug antibodies (ADAs) against fariciamb were detected in plasma using a validated bridging enzyme-linked immunosorbent assay (ELISA). The number of participants with treatment-emergent ADA-positive samples includes post-baseline evaluable participants with at least one treatment-induced (defined as having an ADA-negative sample or missing sample at baseline and any positive post-baseline sample) or treatment-boosted (defined as having an ADA-positive sample at baseline and any positive post-baseline sample with a titer that is equal to or greater than 4-fold baseline titer) ADA-positive sample during the study treatment period. Treatment-unaffected ADA-positive is a post-baseline sample with a titer that is lower than 4-fold the ADA-positive baseline titer (faricimab arm) or the ADA-positive titer prior to first faricimab injection (aflibercept arm).

End point type

Secondary

End point timeframe

Predose at Day 1 (Baseline), Weeks 4, 24, 28, 52, and 72

End point values	Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)	All Faricimab Participants
Number of subjects analysed	274	266	540
Units: Participants
Baseline (BL): Total ADA-Positive	3	4	7
Post-BL: Total ADA-Positive	33	23	56
Post-BL: Treatment-Emergent ADA-Positive	32	21	53
Post-BL: Treatment-Unaffected ADA-Positive	1	2	3

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Part 1: From first dose up to Week 24; Part 2: from Week 24 through Week 72

Adverse event reporting additional description

Safety analysis population: all subjects who received ≥1 study drug injection (faricimab or aflibercept). For Part 2, this included: in Arm A, those with Week 24 treatment or dose hold, or if none, follow-up beyond Day 168; in Arm B, those who received ≥1 faricimab dose. The eye type (study/fellow) in which an ocular AE had occurred is specified.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

Arm A: Faricimab Q4W (Part 1)

Reporting group description

Reporting group title

Arm B: Aflibercept Q4W (Part 1)

Reporting group description

Reporting group title

Arm A: Faricimab Q4W to Faricimab PTI (Part 2)

Reporting group description

Reporting group title

Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)

Reporting group description

In Part 2 (from Week 24 to Week 72), participants received faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure was to be administered during study visits at which no faricimab treatment was administered (according to the PTI dosing regimen).

Serious adverse events	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)	Arm A: Faricimab Q4W to Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)
Total subjects affected by serious adverse events
subjects affected / exposed	12 / 276 (4.35%)	17 / 274 (6.20%)	29 / 270 (10.74%)	26 / 267 (9.74%)
number of deaths (all causes)	1	0	1	2
number of deaths resulting from adverse events	1	0	1	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Breast cancer
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Non-small cell lung cancer metastatic
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatic neoplasm
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostate cancer metastatic
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Breast cancer recurrent
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Shoulder arthroplasty
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pain
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Vascular stent stenosis
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Uterine polyp
subjects affected / exposed	1 / 276 (0.36%)	0 / 274 (0.00%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urogenital prolapse
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cervical polyp
subjects affected / exposed	1 / 276 (0.36%)	0 / 274 (0.00%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute pulmonary oedema
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Product issues
Device malfunction
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Blood pressure increased
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	1 / 276 (0.36%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lumbar vertebral fracture
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sternal fracture
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	2 / 270 (0.74%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Comminuted fracture
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Burns third degree
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ulna fracture
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Vertebral artery hypoplasia
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 276 (0.00%)	2 / 274 (0.73%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 276 (0.36%)	0 / 274 (0.00%)	2 / 270 (0.74%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Coronary artery disease
subjects affected / exposed	0 / 276 (0.00%)	2 / 274 (0.73%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Atrial fibrillation
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arteriosclerosis coronary artery
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	2 / 270 (0.74%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Carotid artery stenosis
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral infarction
subjects affected / exposed	3 / 276 (1.09%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	2 / 3	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Multiple sclerosis
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	1 / 276 (0.36%)	1 / 274 (0.36%)	0 / 270 (0.00%)	2 / 267 (0.75%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Cerebral thrombosis
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral haematoma
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive encephalopathy
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intracranial aneurysm
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	2 / 267 (0.75%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sciatica
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo positional
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Vitreous haemorrhage
Additional description: AEs occurred in the study eye
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal vein occlusion
Additional description: AEs occurred in the study eye
subjects affected / exposed	1 / 276 (0.36%)	1 / 274 (0.36%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal ischaemia
Additional description: AEs occurred in the study eye
subjects affected / exposed	2 / 276 (0.72%)	0 / 274 (0.00%)	0 / 270 (0.00%)	2 / 267 (0.75%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cataract
Additional description: AEs occurred in the study eye
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Macular ischaemia
Additional description: AEs occurred in the study eye
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Macular oedema
Additional description: AEs occurred in the study eye
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tractional retinal detachment
Additional description: AEs occurred in the study eye
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rhegmatogenous retinal detachment
Additional description: AEs occurred in the study eye
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal neovascularisation
Additional description: AEs occurred in the study eye
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Pancreatitis acute
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastric haemorrhage
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Functional gastrointestinal disorder
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	1 / 276 (0.36%)	0 / 274 (0.00%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Skin ulcer
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Glomerulonephritis
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute kidney injury
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chronic kidney disease
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haematuria
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal mass
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	2 / 270 (0.74%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal osteoarthritis
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Gastroenteritis
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 276 (0.00%)	1 / 274 (0.36%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal sepsis
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	0 / 270 (0.00%)	1 / 267 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal infection
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Type 2 diabetes mellitus
subjects affected / exposed	1 / 276 (0.36%)	0 / 274 (0.00%)	0 / 270 (0.00%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus inadequate control
subjects affected / exposed	0 / 276 (0.00%)	0 / 274 (0.00%)	1 / 270 (0.37%)	0 / 267 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 3%

Non-serious adverse events	Arm A: Faricimab Q4W (Part 1)	Arm B: Aflibercept Q4W (Part 1)	Arm A: Faricimab Q4W to Faricimab PTI (Part 2)	Arm B: Aflibercept Q4W to Faricimab PTI (Part 2)
Total subjects affected by non serious adverse events
subjects affected / exposed	62 / 276 (22.46%)	69 / 274 (25.18%)	92 / 270 (34.07%)	87 / 267 (32.58%)
Investigations
Intraocular pressure increased
Additional description: AEs occurred in the study eye
subjects affected / exposed	1 / 276 (0.36%)	8 / 274 (2.92%)	13 / 270 (4.81%)	8 / 267 (3.00%)
occurrences all number	2	8	21	11
Vascular disorders
Hypertension
subjects affected / exposed	20 / 276 (7.25%)	7 / 274 (2.55%)	14 / 270 (5.19%)	8 / 267 (3.00%)
occurrences all number	21	7	14	8
Eye disorders
Dry eye
Additional description: AEs occurred in the study eye
subjects affected / exposed	5 / 276 (1.81%)	9 / 274 (3.28%)	4 / 270 (1.48%)	4 / 267 (1.50%)
occurrences all number	5	9	5	4
Conjunctival haemorrhage
Additional description: AEs occurred in the study eye
subjects affected / exposed	8 / 276 (2.90%)	10 / 274 (3.65%)	11 / 270 (4.07%)	10 / 267 (3.75%)
occurrences all number	9	11	11	11
Vitreous detachment
Additional description: AEs occurred in the study eye
subjects affected / exposed	4 / 276 (1.45%)	2 / 274 (0.73%)	7 / 270 (2.59%)	9 / 267 (3.37%)
occurrences all number	4	2	7	9
Retinal vein occlusion
Additional description: AEs occurred in the study eye
subjects affected / exposed	0 / 276 (0.00%)	2 / 274 (0.73%)	9 / 270 (3.33%)	8 / 267 (3.00%)
occurrences all number	0	3	12	10
Vitreous floaters
Additional description: AEs occurred in the study eye
subjects affected / exposed	7 / 276 (2.54%)	6 / 274 (2.19%)	0 / 270 (0.00%)	9 / 267 (3.37%)
occurrences all number	7	6	0	9
Cataract
Additional description: AEs occurred in the study eye
subjects affected / exposed	2 / 276 (0.72%)	1 / 274 (0.36%)	9 / 270 (3.33%)	9 / 267 (3.37%)
occurrences all number	2	1	9	9
Macular oedema
Additional description: AEs occurred in the study eye
subjects affected / exposed	1 / 276 (0.36%)	2 / 274 (0.73%)	10 / 270 (3.70%)	5 / 267 (1.87%)
occurrences all number	1	2	11	8
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	2 / 276 (0.72%)	10 / 274 (3.65%)	5 / 270 (1.85%)	4 / 267 (1.50%)
occurrences all number	2	10	6	4
Infections and infestations
COVID-19
subjects affected / exposed	10 / 276 (3.62%)	16 / 274 (5.84%)	32 / 270 (11.85%)	25 / 267 (9.36%)
occurrences all number	10	16	32	25
Nasopharyngitis
subjects affected / exposed	6 / 276 (2.17%)	6 / 274 (2.19%)	7 / 270 (2.59%)	10 / 267 (3.75%)
occurrences all number	6	6	8	12
Upper respiratory tract infection
subjects affected / exposed	4 / 276 (1.45%)	5 / 274 (1.82%)	6 / 270 (2.22%)	9 / 267 (3.37%)
occurrences all number	4	5	8	11

More information

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Were there any global substantial amendments to the protocol? Yes

17 Nov 2020

Protocol version 2, the summary of major changes from protocol version 1 were: -Due to extenuating circumstances, such as the Coronavirus Disease 2019 (COVID-19) pandemic, patients may not have had the ability to complete certain trial activities, therefore, in order to ensure adequate power for the primary endpoint, the sample size was increased to mitigate the loss of patients, loss of data, and the potential impact of protocol deviations affecting efficacy analyses.; -Clarified that missed mandatory pharmacokinetic (PK), pharmacodynamic (PD), or anti-drug antibody (ADA) samples be obtained at the next scheduled visit the patient attended.; -Clarified administration guidelines of the National Eye Institute 25-Item Visual Functioning Questionnaire (NEI VFQ-25) to include interviews over the telephone.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase III, Multicenter, Randomized, Double-Masked, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of Faricimab in Patients with Macular Edema Secondary to Branch Retinal Vein Occlusion

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part 1: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye at Week 24

Primary: Part 1: Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye at Week 24

Secondary: Part 1: Change from Baseline in BCVA in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Change from Baseline in BCVA in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline in the Study Eye at Week 24

Secondary: Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline in the Study Eye at Week 24

Secondary: Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Gaining ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Gaining ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Gaining ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Gaining ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Gaining >0 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Gaining >0 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Achieving ≥84 Letters in BCVA (20/20 Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Achieving ≥84 Letters in BCVA (20/20 Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Achieving ≥69 Letters in BCVA (20/40 or Better Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants Achieving ≥69 Letters in BCVA (20/40 or Better Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants with ≤38 Letters in BCVA (20/200 or Worse Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants with ≤38 Letters in BCVA (20/200 or Worse Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Change from Baseline in Central Subfield Thickness in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Change from Baseline in Central Subfield Thickness in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants with Absence of Macular Edema in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants with Absence of Macular Edema in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants with Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants with Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants with Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants with Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants with Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Percentage of Participants with Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24

Secondary: Part 1: Change from Baseline in National Eye Institute 25-Item Visual Functioning Questionnaire (NEI VFQ-25) Composite Score at Week 24

Secondary: Part 1: Change from Baseline in National Eye Institute 25-Item Visual Functioning Questionnaire (NEI VFQ-25) Composite Score at Week 24

Secondary: Parts 1 and 2: Change from Baseline in BCVA in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Change from Baseline in BCVA in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Gaining ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Gaining ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Gaining ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Gaining ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Gaining >0 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Gaining >0 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA from Baseline in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Achieving ≥84 Letters in BCVA (20/20 Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Achieving ≥84 Letters in BCVA (20/20 Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Achieving ≥69 Letters in BCVA (20/40 or Better Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants Achieving ≥69 Letters in BCVA (20/40 or Better Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants with ≤38 Letters in BCVA (20/200 or Worse Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants with ≤38 Letters in BCVA (20/200 or Worse Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Change from Baseline in NEI VFQ-25 Questionnaire Composite Score at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Change from Baseline in NEI VFQ-25 Questionnaire Composite Score at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Change from Baseline in Central Subfield Thickness in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Change from Baseline in Central Subfield Thickness in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants with Absence of Macular Edema in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants with Absence of Macular Edema in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants with Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants with Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants with Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 72

Secondary: Parts 1 and 2: Percentage of Participants with Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 72

Clinical Trial Results:
A Phase III, Multicenter, Randomized, Double-Masked, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of Faricimab in Patients with Macular Edema Secondary to Branch Retinal Vein Occlusion