A Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Participants With Diabetic Macular Edema (YOSEMITE)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03622580
• Collaborator: (none)
• Enrollment: 940
• Locations: 185
• Arms: 3
• Actual Duration (Months): 35.9
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy, safety, and pharmacokinetics of faricimab administered at 8-week intervals or as specified in the protocol following treatment initiation, compared with aflibercept once every 8 weeks (Q8W), in participants with diabetic macular edema (DME).

Condition or Disease	Intervention/Treatment	Phase
Diabetic Macular Edema	Drug: Aflibercept; Drug: Faricimab; Procedure: Sham Procedure	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 940 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicenter, Randomized, Double-Masked, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Patients With Diabetic Macular Edema (YOSEMITE)
• Actual Study Start Date: Sep 5, 2018
• Actual Primary Completion Date: Oct 20, 2020
• Actual Study Completion Date: Sep 3, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A: Faricimab 6 mg Q8W Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Drug: Faricimab; Faricimab 6 mg was administered by IVT injection into the study eye either once every 8 weeks (Q8W) in arm A or according to a personalized treatment interval (PTI) in arm B.; Other Names: VABYSMO™ RO6867461 RG7716 ; Procedure: Sham Procedure; The sham is a procedure that mimics an IVT injection and involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. It was administered to participants in all three treatments arms at applicable clinic visits to maintain masking among treatment arms.
Experimental: B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections once every 4 weeks (Q4W), 8 weeks (Q8W), 12 weeks (Q12W), or 16 weeks (Q16W) up to Week 96, followed by the final study visit at Week 100.	Drug: Faricimab; Faricimab 6 mg was administered by IVT injection into the study eye either once every 8 weeks (Q8W) in arm A or according to a personalized treatment interval (PTI) in arm B.; Other Names: VABYSMO™ RO6867461 RG7716 ; Procedure: Sham Procedure; The sham is a procedure that mimics an IVT injection and involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. It was administered to participants in all three treatments arms at applicable clinic visits to maintain masking among treatment arms.
Active Comparator: C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	Drug: Aflibercept; Aflibercept 2 mg was administered by intravitreal (IVT) injection into the study eye once every 8 weeks (Q8W).; Other Names: Eylea ; Procedure: Sham Procedure; The sham is a procedure that mimics an IVT injection and involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. It was administered to participants in all three treatments arms at applicable clinic visits to maintain masking among treatment arms.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations [From Baseline through Week 56]

   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 letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded. 97.5% CI is a rounding of 97.52% CI.

Secondary Outcome Measures

1. Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale at Week 52, ITT and Treatment-Naive Populations [Baseline and Week 52]

   The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 97.5% confidence interval (CI) is a rounding of 97.52% CI.

2. Change From Baseline in BCVA in the Study Eye Over Time, ITT Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

   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 letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded. 95% CI is a rounding of 95.04% CI.

3. Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

   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 attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline BCVA (continuous), baseline BCVA (<64 vs. ≥64 letters), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

4. Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population [Baseline, average of Weeks 48, 52, and 56]

   BCVA was measured on the 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. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

5. Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

   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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

6. Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

   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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

7. Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

   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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

8. Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

   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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

9. Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population [Baseline, average of Weeks 48, 52, and 56]

   BCVA was measured on the 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. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

10. Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

11. Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

12. Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

13. Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

14. Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population [Baseline, average of Weeks 48, 52, and 56]

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

15. Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

16. Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

17. Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

18. Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population [Baseline, average of Weeks 48, 52, and 56]

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

19. Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

20. Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

21. Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

22. Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations [Baseline, average of Weeks 48, 52, and 56]

    BCVA was measured on the 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. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

23. Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

24. Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

25. Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations [Baseline, average of Weeks 48, 52, and 56]

    BCVA was measured on the 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. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥69 vs. <69 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

26. Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥69 vs. <69 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

27. Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥69 vs. <69 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

28. Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations [Baseline, average of Weeks 48, 52, and 56]

    BCVA was measured on the 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. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

29. Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    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 letter score from baseline indicates an improvement invisual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

30. Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, Treatment-Naive Population [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    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 attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

31. Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population [Baseline, Weeks 16, 52, and 96]

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

32. Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 16, 52, and 96]

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

33. Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population [Baseline, Weeks 16, 52, and 96]

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

34. Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 16, 52, and 96]

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

35. Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population [Baseline, Weeks 16, 52, and 96]

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

36. Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 16, 52, and 96]

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

37. Percentage of Participants Without Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed New PDR at Week 52, ITT and Treatment-Naive Populations [Baseline and Week 52]

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). PDR was defined as an ETDRS DRSS score of ≥61 on the 7-field/4-wide field color fundus photographs assessment by a central reading center. The weighted percentages of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% CI is a rounding of 95.04% CI.

38. Percentage of Participants Without High-Risk Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed High-Risk PDR at Week 52, ITT and Treatment-Naive Populations [Baseline and Week 52]

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced PDR. High-risk PDR was defined as an ETDRS DRSS score of ≥71 on the 7-field/4-wide field color fundus photographs assessment by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% CI is a rounding of 95.04% CI.

39. Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, ITT Population [Week 52]

40. Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, Treatment-Naive Population [Week 52]

41. Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, ITT Population [Week 96]

42. Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, Treatment-Naive Population [Week 96]

43. Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 52 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations [From start of PTI (Week 12 or later) until Week 52]

44. Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 96 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations [From start of PTI (Week 12 or later) until Week 96]

45. Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations [From Baseline through Week 56]

    Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.

46. Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.

47. Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (<64 vs. ≥64 letters), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.

48. Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations [Average of Weeks 48, 52, and 56]

    Absence of diabetic macular edema was defined as achieving a central subfield thickness (CST) of <325 microns in the study eye. CST was defined as the distance between the internal limiting membrane and Bruch's membrane. For each participant, an average CST value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

49. Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    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 estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

50. Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, Treatment-Naive Population [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    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 estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

51. Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    Retinal dryness was defined as achieving a central subfield thickness (ILM-BM) of <280 microns. 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 estimates of the percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

52. Percentage of Participants With Retinal Dryness in the Study Eye Over Time, Treatment-Naive Population [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100]

    Retinal dryness was defined as achieving a central subfield thickness (ILM-BM) of <280 microns. 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 estimates of the percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled patients. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

53. Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population [Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100]

    Intraretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

54. Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100]

    Intraretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

55. Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population [Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100]

    Subretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

56. Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100]

    Subretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

57. Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population [Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100]

    Intraretinal fluid and subretinal fluid were measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

58. Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, Treatment-Naive Population [Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100]

    Intraretinal fluid and subretinal fluid were measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

59. Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Composite Score Over Time [Baseline, Weeks 24, 52, and 100]

60. Percentage of Participants With at Least One Ocular Adverse Event [Up to 2 years]

61. Percentage of Participants With at Least One Non-Ocular Adverse Event [Up to 2 years]

62. Plasma Concentration of Faricimab Over Time [Pre-dose on Day 1; Weeks 4, 28, 52, 76, and 100; and at Early Termination Visit (up to 2 years)]

63. Percentage of Participants With Presence of Anti-Drug Antibodies [Pre-dose on Day 1; Weeks 4, 28, 52, 76, and 100; and at Early Termination Visit (up to 2 years)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Documented diagnosis of diabetes mellitus (Type 1 or Type 2)

• Hemoglobin A1c (HbA1c) of less than or equal to (≤) 10% within 2 months prior to Day 1

• Macular thickening secondary to diabetic macular edema (DME) involving the center of the fovea

• Decreased visual acuity attributable primarily to DME

• Ability and willingness to undertake all scheduled visits and assessments

• For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 3 months after the final dose of study treatment

Exclusion Criteria:

• Currently untreated diabetes mellitus or previously untreated patients who initiated oral or injectable anti-diabetic medication within 3 months prior to Day 1

• Uncontrolled blood pressure, defined as a systolic value greater than (>)180 millimeters of mercury (mmHg) and/or a diastolic value >100 mmHg while a patient is at rest

• Currently pregnant or breastfeeding, or intend to become pregnant during the study

• Treatment with panretinal photocoagulation or macular laser within 3 months prior to Day 1 to the study eye

• Any intraocular or periocular corticosteroid treatment within the past 6 months prior to Day 1 to the study eye

• Prior administration of IVT faricimab in either eye

• Active intraocular or periocular infection or active intraocular inflammation in the study eye

• Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision in the study eye

• Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than DME in the study eye

• Other protocol-specified inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barnet Dulaney Perkins Eye Center	Mesa	Arizona	United States	85206
2	Arizona Retina and Vitreous Consultants	Phoenix	Arizona	United States	85021
3	Retina Associates Southwest PC	Tucson	Arizona	United States	85704
4	Retinal Diagnostic Center	Campbell	California	United States	95008
5	Eye Medical Center	Fresno	California	United States	93720
6	East Bay Retina Consultants	Oakland	California	United States	94609
7	Southern CA Desert Retina Cons	Palm Desert	California	United States	92211
8	California Eye Specialists Medical group Inc.	Pasadena	California	United States	91107
9	Retina Consultants, San Diego	Poway	California	United States	92064
10	Retina Consultants of Southern California	Redlands	California	United States	92373
11	Kaiser Permanente Riverside Medical Center	Riverside	California	United States	92505
12	University of California, Davis, Eye Center	Sacramento	California	United States	95817
13	W Coast Retina Med Group Inc	San Francisco	California	United States	94107
14	Orange County Retina Med Group	Santa Ana	California	United States	92705
15	Colorado Retina Associates, PC	Lakewood	Colorado	United States	80228
16	Rand Eye	Deerfield Beach	Florida	United States	33064
17	Retina Care Specialists	Palm Beach Gardens	Florida	United States	33410
18	Retina Specialty Institute	Pensacola	Florida	United States	32503
19	Southern Vitreoretinal Assoc	Tallahassee	Florida	United States	32308
20	Retina Associates of Florida, LLC	Tampa	Florida	United States	33609
21	University of South Florida	Tampa	Florida	United States	33612
22	Georgia Retina PC	Marietta	Georgia	United States	30060
23	Retina Consultants of Hawaii	'Aiea	Hawaii	United States	96701
24	Midwest Eye Institute	Indianapolis	Indiana	United States	46290
25	Wolfe Eye Clinic	West Des Moines	Iowa	United States	50266
26	Retina Associates	Lenexa	Kansas	United States	66215
27	Vitreo-Retinal Consultants	Wichita	Kansas	United States	67214
28	Retina Associates of Kentucky	Lexington	Kentucky	United States	40509
29	Paducah Retinal Center	Paducah	Kentucky	United States	42001
30	Maine Eye Center	Portland	Maine	United States	04101
31	The Retina Care Center	Baltimore	Maryland	United States	21209
32	Johns Hopkins Med; Wilmer Eye Inst	Baltimore	Maryland	United States	21287
33	Retina Group of Washington	Chevy Chase	Maryland	United States	20815
34	Cumberland Valley Retina PC	Hagerstown	Maryland	United States	21740
35	Ophthalmic Consultants of Boston	Boston	Massachusetts	United States	02114
36	Beetham Eye Institute, Joslin Diabetes Center	Boston	Massachusetts	United States	02215
37	Vitreo-Retinal Associates, PC	Worcester	Massachusetts	United States	01605
38	Foundation for Vision Research	Grand Rapids	Michigan	United States	49546
39	Assoc Retinal Consultants PC	Royal Oak	Michigan	United States	48073
40	Associated Retinal Consultants, P.C.	Traverse City	Michigan	United States	49686
41	Vitreoretinal Surgery	Edina	Minnesota	United States	55435
42	Midwest Vision Research Foundation	Chesterfield	Missouri	United States	63017
43	Sierra Eye Associates	Reno	Nevada	United States	89502
44	Mid Atlantic Retina - Wills Eye Hospital	Cherry Hill	New Jersey	United States	08034
45	NJ Retina	Edison	New Jersey	United States	08820
46	Retinal & Ophthalmic Cons PC	Northfield	New Jersey	United States	08225
47	Retina Associates of NJ	Teaneck	New Jersey	United States	07666
48	University of New Mexico	Albuquerque	New Mexico	United States	87131
49	Capital Region Retina	Albany	New York	United States	12206
50	Long Is. Vitreoretinal Consult	Great Neck	New York	United States	11021
51	Retina Vit Surgeons/Central NY	Liverpool	New York	United States	13088
52	MaculaCare, PLLC	New York	New York	United States	10021
53	Island Retina	Shirley	New York	United States	11967
54	Western Carolina Retinal Associate PA	Asheville	North Carolina	United States	28803
55	Char Eye Ear &Throat Assoc	Charlotte	North Carolina	United States	28210
56	Graystone Eye	Hickory	North Carolina	United States	28602
57	Carolina Eye Associates	Southern Pines	North Carolina	United States	28387
58	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
59	Cincinnati Eye Institute	Cincinnati	Ohio	United States	45242
60	Retina Assoc of Cleveland Inc	Cleveland	Ohio	United States	44122
61	OSU Eye Physicians & Surgeons	Columbus	Ohio	United States	43212
62	Midwest Retina	Dublin	Ohio	United States	43016
63	Retina Vitreous Center	Edmond	Oklahoma	United States	73013
64	Retina Northwest	Portland	Oregon	United States	97221
65	Black Hills Eye Institute	Rapid City	South Dakota	United States	57701
66	Charles Retina Institute	Memphis	Tennessee	United States	38119
67	Retina Res Institute of Texas	Abilene	Texas	United States	79606
68	Austin Clinical Research LLC	Austin	Texas	United States	78750
69	Retina Consultants of Texas	Bellaire	Texas	United States	77401
70	Texas Retina Associates	Dallas	Texas	United States	75231
71	Retina Specialists	DeSoto	Texas	United States	75115
72	Valley Retina Institute P.A.	Harlingen	Texas	United States	78550
73	Retina & Vitreous of Texas	Houston	Texas	United States	77025
74	Med Center Ophthalmology Assoc	San Antonio	Texas	United States	78240
75	Eye Care Assoc of East Texas	Tyler	Texas	United States	75701
76	Strategic Clinical Research Group, LLC	Willow Park	Texas	United States	76087
77	Retina Associates of Utah	Salt Lake City	Utah	United States	84107
78	University of Utah; Division of Gastroenterology/Hepatology	Salt Lake City	Utah	United States	84132
79	University of Vermont Medical Center; Investigational Drug Service, Pharmacy Department/Baird 1	Burlington	Vermont	United States	05401
80	Emerson Clinical Research Institute	Falls Church	Virginia	United States	22042
81	Piedmont Eye Center	Lynchburg	Virginia	United States	24502
82	Wagner Macula & Retina Center	Norfolk	Virginia	United States	23502
83	Spokane Eye Clinical Research	Spokane	Washington	United States	99204
84	West Virginia University Eye Institute	Morgantown	West Virginia	United States	26506
85	University of Wisconsin	Madison	Wisconsin	United States	53792
86	LKH-Univ.Klinikum Graz; Universitäts-Augenklinik	Graz		Austria	8036
87	Kepler Universitätskliniken GmbH - Med Campus III; Abt. für Augenheilkunde	Linz		Austria	4021
88	Medizinische Universität Wien; Universitätsklinik für Augenheilkunde und Optometrie	Wien		Austria	1090
89	Hanusch Krankenhaus; Abteilung für Augenkrankheiten mit Augen-Tagesklinik	Wien		Austria	1140
90	Medical Center for Eye Health - Focus Ltd	Sofia		Bulgaria	1303
91	Pentagram Eye Hospital (Medical Center "Pentagram")	Sofia		Bulgaria	1309
92	Spec. Ophth. Hospital for Active Treatment- Academic Pashev	Sofia		Bulgaria	1517
93	Specialized Hospital for Active Treatment of Eye Diseases Zora	Sofia		Bulgaria	1784
94	Ambulatory - Medical Center for Specialized Medical Assistance - "Eye Clinic Sveta Petka" Ltd	Varna		Bulgaria	9002
95	Hopital Pellegrin; Ophtalmologie	Bordeaux		France	33000
96	Pole Vision Val d'Ouest; Ophtalmologie	Ecully		France	69130
97	Centre Paradis Monticelli; Ophtalmologie	Marseille		France	13008
98	CHU Nantes - Hôtel Dieu; Ophthalmology	Nantes		France	44093
99	Centre Odeon; Exploration Ophtalmologique	Paris		France	75006
100	Hopital Lariboisiere; Ophtalmologie	Paris		France	75010
101	Universitäts-Augenklinik Bonn	Bonn		Germany	53127
102	Universitätsmedizin Göttingen Georg-August-Universität; Klinik für Augenheilkunde 3.B1.266	Göttingen		Germany	37075
103	Medizinische Hochschule Hannover, Klinik für Augenheilkunde	Hannover		Germany	30625
104	Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Augenklinik und Poliklinik	Mainz		Germany	55131
105	Augenabteilung am St. Franziskus-Hospital	Münster		Germany	48145
106	Universitätsklinikum Münster; Augenheilkunde	Münster		Germany	48149
107	Budapest Retina Associates Kft.	Budapest		Hungary	1133
108	Debreceni Egyetem Klinikai Kozpont; Szemeszeti Klinika	Debrecen		Hungary	4032
109	Ganglion Medial Center	Pécs		Hungary	7621
110	Szegedi Tudományegyetem ÁOK; Department of Ophtalmology	Szeged		Hungary	6720
111	Markusovszky Egyetemi Oktatokorhaz ; SZEMESZET	Szombathely		Hungary	9700
112	Zala Megyei Kórház; SZEMESZET	Zalaegerszeg		Hungary	8900
113	Rambam Medical Center; Opthalmology	Haifa		Israel	3109601
114	Hadassah MC; Ophtalmology	Jerusalem		Israel	9112001
115	Rabin MC; Ophtalmology	Petach Tikva		Israel	4941492
116	Kaplan Medical Center	Rehovot		Israel	7610001
117	Tel Aviv Sourasky MC; Ophtalmology	Tel Aviv		Israel	6423906
118	Ospedale Clinicizzato SS Annunziata; Clinica Oftalmologica	Chieti	Abruzzo	Italy	66100
119	Fondazione G.B. Bietti Per Lo Studio E La Ricerca in Oftalmologia-Presidio Ospedaliero Britannico	Roma	Lazio	Italy	00198
120	UNIVERSITA' DEGLI STUDI DI GENOVA - Di.N.O.G.;CLINICA OCULISTICA	Genova	Liguria	Italy	16132
121	Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico-Clinica Regina Elena;U.O.C Oculistica	Milano	Lombardia	Italy	20100
122	Irccs Ospedale San Raffaele;U.O. Oculistica	Milano	Lombardia	Italy	20132
123	Azienda Ospedaliera di Perugia Ospedale S. Maria Della Misericordia; Clinica Oculistica	Perugia	Umbria	Italy	06129
124	Sugita Eye Hospital	Aichi		Japan	460-0008
125	Nagoya University Hospital	Aichi		Japan	466-8560
126	Nagoya City University Hospital	Aichi		Japan	467-8602
127	Aichi Medical University Hospital	Aichi		Japan	480-1195
128	Toho University Sakura Medical Center	Chiba		Japan	285-8741
129	Hayashi Eye Hospital	Fukuoka		Japan	812-0011
130	Kurume University Hospital	Fukuoka		Japan	830-0011
131	Hokkaido University Hospital	Hokkaido		Japan	060-8648
132	Asahikawa Medical University Hospital	Hokkaido		Japan	078-8510
133	Hyogo Prefectural Amagasaki General Medical Center (Hyogo AGMC)	Hyogo		Japan	660-8550
134	Kozawa eye hospital and diabetes center	Ibaraki		Japan	310-0845
135	St. Marianna University Hospital	Kanagawa		Japan	216-8511
136	Ideta Eye Hospital	Kumamoto		Japan	860-0027
137	Kyoto University Hospital	Kyoto		Japan	606-8507
138	Mie University Hospital	Mie		Japan	514-8507
139	University of Miyazaki Hospital	Miyazaki		Japan	889-1692
140	Nara Medical University Hospital	Nara		Japan	634-8522
141	Kitano Hospital	Osaka		Japan	530-8480
142	Osaka City University Hospital	Osaka		Japan	545-8586
143	National Defense Medical College Hospital	Saitama		Japan	359-8513
144	Shiga University Of Medical Science Hospital	Shiga		Japan	520-2192
145	Seirei Hamamatsu General Hospital	Shizuoka		Japan	430-8558
146	Tokushima University Hospital	Tokushima		Japan	770-8503
147	Tokyo Women's Medical University Hospital	Tokyo		Japan	162-8666
148	Kyorin University Hospital	Tokyo		Japan	181-8611
149	Tokyo Medical University Hachioji Medical Center	Tokyo		Japan	193-0998
150	Yamaguchi University Hospital	Yamaguchi		Japan	755-8505
151	Centro Oftalmológico Mira, S.C	Del. Cuauhtemoc	Mexico CITY (federal District)	Mexico	06760
152	Macula Retina Consultores	Mexico, D.F.		Mexico	01120
153	Hospital de la Ceguera APEC	Mexico, D.F.		Mexico	04030
154	Instituto Mexicano de Oftalmologia I.A.P.	Querétaro		Mexico	76090
155	Mácula D&T	Lima		Peru	27
156	Oftalmosalud Srl	Lima		Peru	27
157	TG Laser Oftalmica	Lima		Peru	27
158	Oftalmolaser	Lima		Peru	Lima 33
159	Szpital sw. Lukasza	Bielsko-Biala		Poland	43-309
160	Szpital Specjalistyczny nr 1; Oddzial Okulistyki	Bytom		Poland	41-902
161	Dobry Wzrok Sp Z O O	Gdańsk		Poland	80-402
162	Gabinet Okulistyczny Prof Edward Wylegala	Katowice		Poland	40-594
163	Centrum Medyczne UNO-MED	Krakow		Poland	31-070
164	Optomed Sp. z o.o.	Rybnik		Poland	44-203
165	Kliniczny Szpital Wojewodzki nr 1 im. F. Chopina; Klinika Okulistyki	Rzeszów		Poland	35-055
166	SPEKTRUM Osrodek Okulistyki Klinicznej	Wroclaw		Poland	53-334
167	Clinic Optimed	UFA	Baskortostan	Russian Federation	450059
168	FSBI "Scientific Research Institute of Eye Diseases" of Russian Academy of medical Sciences	Moscow		Russian Federation	119435
169	Medical Military Academy n.a S.M.Kirov	St.Petersburg		Russian Federation	194044
170	Nemocnica s poliklinikou Trebišov, a.s.	Trebišov		Slovakia	075 01
171	Fakultna nemocnica Trencin Ocna klinika	Trencin		Slovakia	911 71
172	Fakultna nemocnica s poliklinikou Zilina; Ocne oddelenie	Zilina		Slovakia	012 07
173	Instituto Oftalmologico Gomez Ulla; Servicio de Oftalmologia	Santiago de Compostela	LA Coruña	Spain	15706
174	Hospital Universitario de Gran Canaria; Servicio de oftalmologia	Las Palmas de Gran Canaria	LAS Palmas	Spain	35016
175	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid	Spain	28222
176	Clinica Universitaria de Navarra; Servicio de Oftalmologia	Pamplona	Navarra	Spain	31008
177	Complejo Hospitalario Universitario Albacete; Servicio de oftalmologia	Albacete		Spain	02006
178	VISSUM Instituto Oftalmológico de Alicante	Alicante		Spain	03016
179	Centro de Oftalmologia Barraquer; Servicio Oftalmologia	Barcelona		Spain	08021
180	Hospital Clinic de Barcelona; Consultas Externas Oftalmologia	Barcelona		Spain	08028
181	Hospital de Santa Creu I Sant Pau; Servicio de Oftalmologia	Barcelona		Spain	08041
182	Clinica Universitaria de Navarra; Servicio de Oftalmologia	Madrid		Spain	28027
183	Hacettepe University Medical Faculty; Department of Ophthalmology	Ankara		Turkey	06100
184	Ege University Medical Faculty; Department of Ophthalmology	Izmir		Turkey	35100
185	Selcuk University Faculty of Medicine; Department Of Ophthalmology	Konya		Turkey	42130

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Jun 20, 2019
• Statistical Analysis Plan - Oct 15, 2020

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03622580
• Other Study ID Numbers: GR40349; 2017-005104-10
• First Posted: Aug 9, 2018
• Last Update Posted: Apr 6, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Macular Edema; Edema; Aflibercept

Study Results

Participant Flow

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Period Title: Overall Study
STARTED	315	313	312
Received at Least One Dose of Study Drug	313	313	311
Completed up to Week 56	291	289	292
COMPLETED	0	0	0
NOT COMPLETED	315	313	312

Baseline Characteristics

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W	Total
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	Total of all reporting groups
Overall Participants	315	313	312	940
Age (Years) [Mean (Standard Deviation) ]
ITT Population	61.6 (9.5)	62.8 (10.0)	62.2 (9.6)	62.2 (9.7)
Treatment-Naive Population	61.0 (9.6)	62.5 (10.3)	62.2 (9.9)	61.9 (10.0)
Sex: Female, Male (Count of Participants)
Female	128 40.6%	116 37.1%	134 42.9%	378 40.2%
Male	187 59.4%	197 62.9%	178 57.1%	562 59.8%
Female	93 29.5%	91 29.1%	108 34.6%	292 31.1%
Male	145 46%	154 49.2%	134 42.9%	433 46.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	37 11.7%	40 12.8%	37 11.9%	114 12.1%
Not Hispanic or Latino	273 86.7%	268 85.6%	272 87.2%	813 86.5%
Unknown or Not Reported	5 1.6%	5 1.6%	3 1%	13 1.4%
Hispanic or Latino	31 9.8%	32 10.2%	31 9.9%	94 10%
Not Hispanic or Latino	202 64.1%	210 67.1%	208 66.7%	620 66%
Unknown or Not Reported	5 1.6%	3 1%	3 1%	11 1.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	6 1.9%	5 1.6%	7 2.2%	18 1.9%
Asian	31 9.8%	26 8.3%	27 8.7%	84 8.9%
Native Hawaiian or Other Pacific Islander	2 0.6%	0 0%	3 1%	5 0.5%
Black or African American	22 7%	25 8%	12 3.8%	59 6.3%
White	241 76.5%	240 76.7%	253 81.1%	734 78.1%
More than one race	0 0%	1 0.3%	0 0%	1 0.1%
Unknown or Not Reported	13 4.1%	16 5.1%	10 3.2%	39 4.1%
American Indian or Alaska Native	4 1.3%	3 1%	6 1.9%	13 1.4%
Asian	21 6.7%	18 5.8%	20 6.4%	59 6.3%
Native Hawaiian or Other Pacific Islander	2 0.6%	0 0%	2 0.6%	4 0.4%
Black or African American	17 5.4%	24 7.7%	9 2.9%	50 5.3%
White	181 57.5%	186 59.4%	196 62.8%	563 59.9%
More than one race	0 0%	1 0.3%	0 0%	1 0.1%
Unknown or Not Reported	13 4.1%	13 4.2%	9 2.9%	35 3.7%
Number of Participants by Previous Treatment Status with Intravitreal Anti-VEGF Agents (Count of Participants)
Treatment-Naive	238 75.6%	245 78.3%	242 77.6%	725 77.1%
Previously Treated	77 24.4%	68 21.7%	70 22.4%	215 22.9%
Region of Enrollment (Count of Participants)
United States and Canada	167 53%	168 53.7%	168 53.8%	503 53.5%
Asia	21 6.7%	19 6.1%	20 6.4%	60 6.4%
Rest of the World	127 40.3%	126 40.3%	124 39.7%	377 40.1%
United States and Canada	130 41.3%	134 42.8%	135 43.3%	399 42.4%
Asia	14 4.4%	14 4.5%	15 4.8%	43 4.6%
Rest of the World	94 29.8%	97 31%	92 29.5%	283 30.1%
Number of Participants by the Eye Chosen as the Study Eye (Left or Right) (Count of Participants)
Left Eye	150 47.6%	172 55%	151 48.4%	473 50.3%
Right Eye	165 52.4%	141 45%	161 51.6%	467 49.7%
Left Eye	117 37.1%	130 41.5%	117 37.5%	364 38.7%
Right Eye	121 38.4%	115 36.7%	125 40.1%	361 38.4%
Baseline Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye (ETDRS Letters) [Mean (Standard Deviation) ]
ITT Population	62.0 (9.9)	61.9 (10.2)	62.2 (9.5)	62.0 (9.9)
Treatment-Naive Population	62.3 (9.9)	61.8 (10.7)	62.6 (9.2)	62.2 (9.9)
Number of Participants by the Baseline BCVA Letter Score Categories in the Study Eye (Count of Participants)
≤38 Letters	15 4.8%	12 3.8%	12 3.8%	39 4.1%
39 to 63 Letters	132 41.9%	126 40.3%	132 42.3%	390 41.5%
≥64 Letters	168 53.3%	175 55.9%	168 53.8%	511 54.4%
Missing/Invalid BCVA	0 0%	0 0%	0 0%	0 0%
≤38 Letters	10 3.2%	11 3.5%	8 2.6%	29 3.1%
39 to 63 Letters	98 31.1%	95 30.4%	100 32.1%	293 31.2%
≥64 Letters	130 41.3%	139 44.4%	134 42.9%	403 42.9%
Missing/Invalid BCVA	0 0%	0 0%	0 0%	0 0%
Number of Participants by Baseline Diabetic Retinopathy Severity (DRS) Status in the Study Eye (Count of Participants)
1 - Diabetic Retinopathy (DR) Absent	2 0.6%	3 1%	4 1.3%	9 1%
2 - DR Questionable / Microaneurysms Only	4 1.3%	6 1.9%	10 3.2%	20 2.1%
3 - Mild Non-Proliferative Diabetic Retinopathy (NPDR)	84 26.7%	92 29.4%	83 26.6%	259 27.6%
4 - Moderate NPDR	84 26.7%	86 27.5%	85 27.2%	255 27.1%
5 - Moderately Severe NPDR	67 21.3%	59 18.8%	54 17.3%	180 19.1%
6 - Severe NPDR	46 14.6%	40 12.8%	49 15.7%	135 14.4%
7 - Mild Proliferative Diabetic Retinopathy (PDR)	16 5.1%	11 3.5%	9 2.9%	36 3.8%
8 - Moderate PDR	6 1.9%	9 2.9%	7 2.2%	22 2.3%
9 - High Risk PDR (DRS Level 71)	0 0%	1 0.3%	2 0.6%	3 0.3%
10 - High Risk PDR (DRS Level 75)	0 0%	0 0%	0 0%	0 0%
11 - Advanced PDR (DRS Level 81)	0 0%	0 0%	0 0%	0 0%
12 - Advanced PDR (DRS Level 85)	0 0%	0 0%	0 0%	0 0%
Cannot Grade	4 1.3%	5 1.6%	7 2.2%	16 1.7%
Missing	2 0.6%	1 0.3%	2 0.6%	5 0.5%
1 - Diabetic Retinopathy (DR) Absent	2 0.6%	3 1%	2 0.6%	7 0.7%
2 - DR Questionable / Microaneurysms Only	1 0.3%	4 1.3%	4 1.3%	9 1%
3 - Mild Non-Proliferative Diabetic Retinopathy (NPDR)	65 20.6%	66 21.1%	57 18.3%	188 20%
4 - Moderate NPDR	56 17.8%	58 18.5%	65 20.8%	179 19%
5 - Moderately Severe NPDR	50 15.9%	52 16.6%	48 15.4%	150 16%
6 - Severe NPDR	40 12.7%	38 12.1%	46 14.7%	124 13.2%
7 - Mild Proliferative Diabetic Retinopathy (PDR)	13 4.1%	9 2.9%	6 1.9%	28 3%
8 - Moderate PDR	6 1.9%	9 2.9%	6 1.9%	21 2.2%
9 - High Risk PDR (DRS Level 71)	0 0%	0 0%	2 0.6%	2 0.2%
10 - High Risk PDR (DRS Level 75)	0 0%	0 0%	0 0%	0 0%
11 - Advanced PDR (DRS Level 81)	0 0%	0 0%	0 0%	0 0%
12 - Advanced PDR (DRS Level 85)	0 0%	0 0%	0 0%	0 0%
Cannot Grade	4 1.3%	5 1.6%	5 1.6%	14 1.5%
Missing	1 0.3%	1 0.3%	1 0.3%	3 0.3%
Baseline Central Subfield Thickness in the Study Eye (microns) [Mean (Standard Deviation) ]
ITT Population	492.3 (135.8)	485.8 (130.8)	484.5 (131.1)	487.5 (132.5)
Treatment-Naive Population	488.8 (136.8)	483.5 (127.3)	486.8 (130.4)	486.3 (131.3)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations
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 letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded. 97.5% CI is a rounding of 97.52% CI.
Time Frame	From Baseline through Week 56

Outcome Measure Data

Analysis Population Description

ITT Population and Treatment-Naive Population

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Measure Participants	315	313	312
ITT Population	10.7	11.6	10.9
Treatment-Naive Population	10.6	11.4	11.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	Three hypotheses were tested in order for each faricimab arm (Q8W or PTI) separately against the aflibercept arm using a graph-based testing procedure. The analysis presented here is for the non-inferiority of Arm A: Faricimab 6 mg Q8W compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower bound of the two-sided 97.52% confidence interval for the difference in adjusted means for the faricimab 6 mg Q8W and the active comparator (aflibercept 2 mg Q8W) arms was greater than -4 letters, then faricimab 6 mg Q8W was considered non-inferior to aflibercept 2 mg Q8W. Non-inferiority was tested one-sided at a significance level of α = 0.0248.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 97.5%; -2.0 to 1.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.79
	Estimation Comments	The difference in adjusted means was calculated as Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W in the ITT Population.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	Three hypotheses were tested in order for each faricimab arm (Q8W or PTI) separately against the aflibercept arm using a graph-based testing procedure. The analysis presented here is for the non-inferiority of Arm B: Faricimab 6 mg PTI compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower bound of the two-sided 97.52% confidence interval for the difference in adjusted means for the faricimab 6 mg PTI and the active comparator (aflibercept 2 mg Q8W) arms was greater than -4 letters, then faricimab 6 mg PTI was considered non-inferior to aflibercept 2 mg Q8W. Non-inferiority was tested one-sided at a significance level of α = 0.0248.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 97.5%; -1.1 to 2.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.79
	Estimation Comments	The difference in adjusted means was calculated as Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W in the ITT Population.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	Three hypotheses were tested in order for each faricimab arm (Q8W or PTI) separately against the aflibercept arm using a graph-based testing procedure. The analysis presented here is for the superiority of Arm A: Faricimab 6 mg Q8W compared with Arm C: Aflibercept 2 mg Q8W in the Treatment-Naive Population.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4699
	Comments	Tested at an overall significance level of α = 0.0248.
	Method	Mixed Model for Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 97.5%; -2.8 to 1.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.95
	Estimation Comments	The difference in adjusted means was calculated as Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W in the Treatment-Naive Population.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	Three hypotheses were tested in order for each faricimab arm (Q8W or PTI) separately against the aflibercept arm using a graph-based testing procedure. The analysis presented here is for the superiority of Arm B: Faricimab 6 mg PTI compared with Arm C: Aflibercept 2 mg Q8W in the Treatment-Naive Population.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9650
	Comments	Tested at an overall significance level of α = 0.0248.
	Method	Mixed Model for Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 97.5%; -2.1 to 2.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.94
	Estimation Comments	The difference in adjusted means was calculated as Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W in the Treatment-Naive Population.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	Three hypotheses were tested in order for each faricimab arm (Q8W or PTI) separately against the aflibercept arm using a graph-based testing procedure. The analysis presented here is for the superiority of Arm A: Faricimab 6 mg Q8W compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7967
	Comments	Tested at an overall significance level of α = 0.0248.
	Method	Mixed Model for Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 97.5%; -2.0 to 1.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.79
	Estimation Comments	The difference in adjusted means was calculated as Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W in the ITT Population.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	Three hypotheses were tested in order for each faricimab arm (Q8W or PTI) separately against the aflibercept arm using a graph-based testing procedure. The analysis presented here is for the superiority of Arm B: Faricimab 6 mg PTI compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3772
	Comments	Tested at an overall significance level of α = 0.0248.
	Method	Mixed Model for Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 97.5%; -1.1 to 2.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.79
	Estimation Comments	The difference in adjusted means was calculated as Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W in the ITT Population.

2. Secondary Outcome

Title	Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale at Week 52, ITT and Treatment-Naive Populations
Description	The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 97.5% confidence interval (CI) is a rounding of 97.52% CI.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

ITT Population and Treatment-Naive Population. Only participants with non-missing, valid assessments at Baseline and Week 52 were included in the analysis.

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Measure Participants	237	242	229
ITT Population	46.0 14.6%	42.5 13.6%	35.8 11.5%
Treatment-Naive Population	49.7 15.8%	47.6 15.2%	42.5 13.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	The analysis presented here is for the non-inferiority of Arm A: Faricimab 6 mg Q8W compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower bound of the two-sided 97.52% confidence interval for the difference in CMH weighted percentages of participants for the faricimab 6 mg Q8W and the active comparator (aflibercept 2 mg Q8W) arms was greater than -10%, then faricimab 6 mg Q8W was considered non-inferior to aflibercept 2 mg Q8W.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	10.2
	Confidence Interval	(2-Sided) 97.5%; 0.3 to 20.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	The analysis presented here is for the non-inferiority of Arm B: Faricimab 6 mg PTI compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower bound of the two-sided 97.52% confidence interval for the difference in CMH weighted percentages of participants for the faricimab 6 mg PTI and the active comparator (aflibercept 2 mg Q8W) arms was greater than -10%, then faricimab 6 mg PTI was considered non-inferior to aflibercept 2 mg Q8W.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	6.1
	Confidence Interval	(2-Sided) 97.5%; -3.6 to 15.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	The analysis presented here is for the superiority of Arm A: Faricimab 6 mg Q8W compared with Arm C: Aflibercept 2 mg Q8W in the Treatment-Naive Population.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1761
	Comments	Tested at an overall significance level of α = 0.0248.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	7.2
	Confidence Interval	(2-Sided) 97.5%; -4.6 to 18.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	The analysis presented here is for the superiority of Arm B: Faricimab 6 mg PTI compared with Arm C: Aflibercept 2 mg Q8W in the Treatment-Naive Population.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3539
	Comments	Tested at an overall significance level of α = 0.0248.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	4.8
	Confidence Interval	(2-Sided) 97.5%; -6.7 to 16.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	The analysis presented here is for the superiority of Arm A: Faricimab 6 mg Q8W compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0237
	Comments	Tested at an overall significance level of α = 0.0248.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	10.2
	Confidence Interval	(2-Sided) 97.5%; 0.3 to 20.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	The analysis presented here is for the superiority of Arm B: Faricimab 6 mg PTI compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1677
	Comments	Tested at an overall significance level of α = 0.0248.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	6.1
	Confidence Interval	(2-Sided) 97.5%; -3.6 to 15.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in BCVA in the Study Eye Over Time, ITT Population
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 letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded. 95% CI is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population
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 attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline BCVA (continuous), baseline BCVA (<64 vs. ≥64 letters), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population
Description	BCVA was measured on the 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. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, average of Weeks 48, 52, and 56

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Measure Participants	271	276	276
Gaining ≥15 Letters	29.2 9.3%	35.5 11.3%	31.8 10.2%
Gaining ≥10 Letters	57.2 18.2%	58.3 18.6%	57.6 18.5%
Gaining ≥5 Letters	78.9 25%	79.6 25.4%	81.4 26.1%
Gaining ≥0 Letters	91.5 29%	94.5 30.2%	91.4 29.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥15 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 95%; -10.0 to 4.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥15 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	3.5
	Confidence Interval	(2-Sided) 95%; -4.0 to 11.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥10 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -8.6 to 7.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥10 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -7.4 to 8.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥5 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -9.1 to 4.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥5 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -8.5 to 4.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥0 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -4.6 to 4.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥0 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	3.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 7.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population
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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population
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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population
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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population
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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population
Description	BCVA was measured on the 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. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, average of Weeks 48, 52, and 56

Outcome Measure Data

Analysis Population Description

Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Measure Participants	200	215	212
Gaining ≥15 Letters	28.6 9.1%	35.5 11.3%	33.8 10.8%
Gaining ≥10 Letters	57.5 18.3%	59.6 19%	57.5 18.4%
Gaining ≥5 Letters	80.0 25.4%	77.2 24.7%	84.5 27.1%
Gaining ≥0 Letters	91.5 29%	93.5 29.9%	91.6 29.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥15 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-5.2
	Confidence Interval	(2-Sided) 95%; -14.0 to 3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥15 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95%; -7.0 to 10.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥10 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -9.5 to 9.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥10 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 95%; -7.1 to 11.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥5 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-4.5
	Confidence Interval	(2-Sided) 95%; -11.9 to 2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥5 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-7.2
	Confidence Interval	(2-Sided) 95%; -14.6 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥0 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -5.5 to 5.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants gaining ≥0 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -3.0 to 7.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population
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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population
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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Secondary Outcome

Title	Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population
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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Secondary Outcome

Title	Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population
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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

15. Secondary Outcome

Title	Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, average of Weeks 48, 52, and 56

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Measure Participants	271	276	276
Avoiding a Loss of ≥15 Letters	98.1 31.1%	98.6 31.5%	98.9 31.7%
Avoiding a Loss of ≥10 Letters	96.3 30.6%	98.2 31.4%	98.1 31.4%
Avoiding a Loss of ≥5 Letters	95.2 30.2%	96.7 30.9%	96.3 30.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants avoiding a loss of ≥15 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -2.8 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants avoiding a loss of ≥15 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -2.2 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants avoiding a loss of ≥10 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -4.6 to 0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants avoiding a loss of ≥10 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -2.2 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants avoiding a loss of ≥5 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -4.5 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants avoiding a loss of ≥5 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -2.6 to 3.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population
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 weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

17. Secondary Outcome

Title	Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population
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 weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

18. Secondary Outcome

Title	Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population
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 weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

19. Secondary Outcome

Title	Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, average of Weeks 48, 52, and 56

Outcome Measure Data

Analysis Population Description

Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Measure Participants	200	215	212
Avoiding a Loss of ≥15 Letters	97.9 31.1%	98.1 31.3%	99.0 31.7%
Avoiding a Loss of ≥10 Letters	96.5 30.6%	97.7 31.2%	98.6 31.6%
Avoiding a Loss of ≥5 Letters	95.0 30.2%	95.8 30.6%	96.2 30.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants avoiding a loss of ≥15 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -3.5 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants avoiding a loss of ≥15 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -3.1 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants avoiding a loss of ≥10 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -5.1 to 0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants avoiding a loss of ≥10 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -3.5 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants avoiding a loss of ≥5 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -5.2 to 2.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants avoiding a loss of ≥5 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -4.1 to 3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population
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 weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

21. Secondary Outcome

Title	Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population
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 weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

22. Secondary Outcome

Title	Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population
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 weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

23. Secondary Outcome

Title	Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations
Description	BCVA was measured on the 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. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, average of Weeks 48, 52, and 56

Outcome Measure Data

Analysis Population Description

ITT Population and Treatment-Naive Population. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Measure Participants	271	276	276
ITT Population	32.1 10.2%	39.1 12.5%	37.0 11.9%
Treatment-Naive Population	31.5 10%	39.2 12.5%	40.2 12.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-4.9
	Confidence Interval	(2-Sided) 95%; -12.6 to 2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -5.9 to 9.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-8.6
	Confidence Interval	(2-Sided) 95%; -17.8 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -9.9 to 8.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population
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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

25. Secondary Outcome

Title	Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population
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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

26. Secondary Outcome

Title	Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations
Description	BCVA was measured on the 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. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥69 vs. <69 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, average of Weeks 48, 52, and 56

Outcome Measure Data

Analysis Population Description

ITT Population and Treatment-Naive Population. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Measure Participants	271	276	276
ITT Population	71.6 22.7%	77.1 24.6%	74.8 24%
Treatment-Naive Population	72.7 23.1%	75.7 24.2%	77.4 24.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 95%; -10.2 to 3.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	2.4
	Confidence Interval	(2-Sided) 95%; -4.3 to 9.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-4.7
	Confidence Interval	(2-Sided) 95%; -12.6 to 3.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -8.9 to 6.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

27. Secondary Outcome

Title	Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population
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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥69 vs. <69 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

28. Secondary Outcome

Title	Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population
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 letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥69 vs. <69 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

29. Secondary Outcome

Title	Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations
Description	BCVA was measured on the 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. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, average of Weeks 48, 52, and 56

Outcome Measure Data

Analysis Population Description

ITT Population and Treatment-Naive Population. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Measure Participants	271	276	276
ITT Population	2.3 0.7%	1.9 0.6%	1.7 0.5%
Treatment-Naive Population	2.6 0.8%	1.9 0.6%	1.8 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -1.8 to 2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -2.2 to 2.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -2.0 to 3.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -2.6 to 2.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

30. Secondary Outcome

Title	Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population
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 letter score from baseline indicates an improvement invisual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

31. Secondary Outcome

Title	Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, Treatment-Naive Population
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 attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

32. Secondary Outcome

Title	Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population
Description	The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 16, 52, and 96

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

33. Secondary Outcome

Title	Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population
Description	The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 16, 52, and 96

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

34. Secondary Outcome

Title	Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population
Description	The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 16, 52, and 96

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

35. Secondary Outcome

Title	Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population
Description	The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 16, 52, and 96

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

36. Secondary Outcome

Title	Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population
Description	The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 16, 52, and 96

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

37. Secondary Outcome

Title	Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population
Description	The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 16, 52, and 96

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

38. Secondary Outcome

Title	Percentage of Participants Without Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed New PDR at Week 52, ITT and Treatment-Naive Populations
Description	The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). PDR was defined as an ETDRS DRSS score of ≥61 on the 7-field/4-wide field color fundus photographs assessment by a central reading center. The weighted percentages of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% CI is a rounding of 95.04% CI.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

ITT Population and Treatment-Naive Population. Only participants with non-missing, valid assessments at Baseline and Week 52 were included in the analysis.

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Measure Participants	219	224	214
ITT Population	0.9 0.3%	0.9 0.3%	0.5 0.2%
Treatment-Naive Population	0.0 0%	1.2 0.4%	0.6 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -1.1 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95.04%; -1.1 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.9 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -1.5 to 2.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

39. Secondary Outcome

Title	Percentage of Participants Without High-Risk Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed High-Risk PDR at Week 52, ITT and Treatment-Naive Populations
Description	The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity levels ranging from absence of retinopathy to advanced PDR. High-risk PDR was defined as an ETDRS DRSS score of ≥71 on the 7-field/4-wide field color fundus photographs assessment by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% CI is a rounding of 95.04% CI.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

ITT Population and Treatment-Naive Population. Only participants with non-missing, valid assessments at Baseline and Week 52 were included in the analysis.

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Measure Participants	237	241	227
ITT Population	0.4 0.1%	0.0 0%	0.0 0%
Treatment-Naive Population	0.0 0%	0.0 0%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; 0.0 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; 0.0 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; 0.0 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

40. Secondary Outcome

Title	Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, ITT Population
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 52.

Arm/Group Title	B: Faricimab 6 mg PTI
Arm/Group Description	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.
Measure Participants	286
Once Every 4 Weeks	10.8 3.4%
Once Every 8 Weeks	15.4 4.9%
Once Every 12 Weeks	21.0 6.7%
Once Every 16 Weeks	52.8 16.8%

41. Secondary Outcome

Title	Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, Treatment-Naive Population
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 52.

Arm/Group Title	B: Faricimab 6 mg PTI
Arm/Group Description	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.
Measure Participants	222
Once Every 4 Weeks	9.0 2.9%
Once Every 8 Weeks	14.4 4.6%
Once Every 12 Weeks	22.1 7%
Once Every 16 Weeks	54.5 17.3%

42. Secondary Outcome

Title	Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, ITT Population
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

43. Secondary Outcome

Title	Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, Treatment-Naive Population
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

44. Secondary Outcome

Title	Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 52 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations
Time Frame	From start of PTI (Week 12 or later) until Week 52

Outcome Measure Data

Analysis Population Description

ITT Population and Treatment-Naive Population. The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 52.

Arm/Group Title	B: Faricimab 6 mg PTI
Arm/Group Description	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.
Measure Participants	286
ITT Population	67.8 21.5%
Treatment-Naive Population	71.6 22.7%

45. Secondary Outcome

Title	Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 96 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations
Time Frame	From start of PTI (Week 12 or later) until Week 96

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

46. Secondary Outcome

Title	Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations
Description	Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	From Baseline through Week 56

Outcome Measure Data

Analysis Population Description

ITT Population and Treatment-Naive Population

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Measure Participants	315	313	312
ITT Population	-206.6	-196.5	-170.3
Treatment-Naive Population	-204.6	-197.5	-173.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the adjusted mean difference for Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W in the ITT Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-36.2
	Confidence Interval	(2-Sided) 95%; -47.8 to -24.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.88
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the adjusted mean difference for Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W in the ITT Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-26.2
	Confidence Interval	(2-Sided) 95%; -37.7 to -14.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.86
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the adjusted mean difference for Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W in the Treatment-Naive Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-31.1
	Confidence Interval	(2-Sided) 95%; -43.6 to -18.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.35
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the adjusted mean difference for Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W in the Treatment-Naive Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-23.9
	Confidence Interval	(2-Sided) 95%; -36.2 to -11.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.28
	Estimation Comments

47. Secondary Outcome

Title	Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population
Description	Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

48. Secondary Outcome

Title	Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population
Description	Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (<64 vs. ≥64 letters), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

49. Secondary Outcome

Title	Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations
Description	Absence of diabetic macular edema was defined as achieving a central subfield thickness (CST) of <325 microns in the study eye. CST was defined as the distance between the internal limiting membrane and Bruch's membrane. For each participant, an average CST value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Average of Weeks 48, 52, and 56

Outcome Measure Data

Analysis Population Description

ITT Population and Treatment-Naive Population. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

Arm/Group Title	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Measure Participants	272	276	275
ITT Population	81.3 25.8%	78.0 24.9%	65.4 21%
Treatment-Naive Population	83.5 26.5%	80.4 25.7%	68.3 21.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	16.0
	Confidence Interval	(2-Sided) 95%; 8.9 to 23.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	12.7
	Confidence Interval	(2-Sided) 95%; 5.4 to 20.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	15.2
	Confidence Interval	(2-Sided) 95%; 7.3 to 23.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	B: Faricimab 6 mg PTI, C: Aflibercept 2 mg Q8W
	Comments	This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	12.5
	Confidence Interval	(2-Sided) 95%; 4.4 to 20.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

50. Secondary Outcome

Title	Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population
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 estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

51. Secondary Outcome

Title	Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, Treatment-Naive Population
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 estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

52. Secondary Outcome

Title	Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population
Description	Retinal dryness was defined as achieving a central subfield thickness (ILM-BM) of <280 microns. 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 estimates of the percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

53. Secondary Outcome

Title	Percentage of Participants With Retinal Dryness in the Study Eye Over Time, Treatment-Naive Population
Description	Retinal dryness was defined as achieving a central subfield thickness (ILM-BM) of <280 microns. 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 estimates of the percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled patients. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

54. Secondary Outcome

Title	Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population
Description	Intraretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

55. Secondary Outcome

Title	Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, Treatment-Naive Population
Description	Intraretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

56. Secondary Outcome

Title	Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population
Description	Subretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

57. Secondary Outcome

Title	Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, Treatment-Naive Population
Description	Subretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

58. Secondary Outcome

Title	Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population
Description	Intraretinal fluid and subretinal fluid were measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. the rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

59. Secondary Outcome

Title	Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, Treatment-Naive Population
Description	Intraretinal fluid and subretinal fluid were measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.
Time Frame	Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

60. Secondary Outcome

Title	Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Composite Score Over Time
Time Frame	Baseline, Weeks 24, 52, and 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

61. Secondary Outcome

Title	Percentage of Participants With at Least One Ocular Adverse Event
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

62. Secondary Outcome

Title	Percentage of Participants With at Least One Non-Ocular Adverse Event
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

63. Secondary Outcome

Title	Plasma Concentration of Faricimab Over Time
Time Frame	Pre-dose on Day 1; Weeks 4, 28, 52, 76, and 100; and at Early Termination Visit (up to 2 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

64. Secondary Outcome

Title	Percentage of Participants With Presence of Anti-Drug Antibodies
Time Frame	Pre-dose on Day 1; Weeks 4, 28, 52, 76, and 100; and at Early Termination Visit (up to 2 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From Baseline until Week 56 (data cutoff for primary completion date)
Adverse Event Reporting Description	Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye. AEs are still being collected until the end of the study and the results will be updated within 1 year of the final collection date.
Arm/Group Title	A: Faricimab 6 mg Q8W		B: Faricimab 6 mg PTI		C: Aflibercept 2 mg Q8W
Arm/Group Description	Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.		Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.		Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
All Cause Mortality
	A: Faricimab 6 mg Q8W		B: Faricimab 6 mg PTI		C: Aflibercept 2 mg Q8W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/313 (2.6%)		9/313 (2.9%)		4/311 (1.3%)
Serious Adverse Events
	A: Faricimab 6 mg Q8W		B: Faricimab 6 mg PTI		C: Aflibercept 2 mg Q8W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	82/313 (26.2%)		77/313 (24.6%)		56/311 (18%)
Blood and lymphatic system disorders
Anaemia	0/313 (0%)	0	2/313 (0.6%)	5	0/311 (0%)	0
Thrombocytopenia	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Cardiac disorders
Acute left ventricular failure	0/313 (0%)	0	1/313 (0.3%)	1	2/311 (0.6%)	2
Acute myocardial infarction	2/313 (0.6%)	2	2/313 (0.6%)	2	4/311 (1.3%)	4
Angina pectoris	1/313 (0.3%)	1	0/313 (0%)	0	1/311 (0.3%)	1
Arrhythmia	0/313 (0%)	0	2/313 (0.6%)	2	0/311 (0%)	0
Atrial fibrillation	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Atrial flutter	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Atrioventricular block complete	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Cardiac arrest	2/313 (0.6%)	2	0/313 (0%)	0	0/311 (0%)	0
Cardiac failure	0/313 (0%)	0	2/313 (0.6%)	2	1/311 (0.3%)	1
Cardiac failure acute	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Cardiac failure congestive	4/313 (1.3%)	8	0/313 (0%)	0	4/311 (1.3%)	5
Cardiovascular disorder	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Chronic left ventricular failure	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Coronary artery disease	2/313 (0.6%)	2	4/313 (1.3%)	4	2/311 (0.6%)	2
Coronary artery stenosis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Left atrial dilatation	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Left ventricular dilatation	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Myocardial infarction	1/313 (0.3%)	1	3/313 (1%)	3	4/311 (1.3%)	4
Myocardial ischaemia	2/313 (0.6%)	2	0/313 (0%)	0	0/311 (0%)	0
Myocarditis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Pericarditis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Ventricular tachyarrhythmia	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Ear and labyrinth disorders
Sudden hearing loss	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Vestibular disorder	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Eye disorders
Angle closure glaucoma	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Cataract	0/313 (0%)	0	1/313 (0.3%)	1	1/311 (0.3%)	1
Diabetic retinal oedema	1/313 (0.3%)	1	1/313 (0.3%)	1	0/311 (0%)	0
Diabetic retinopathy	3/313 (1%)	3	1/313 (0.3%)	1	1/311 (0.3%)	1
Glaucoma	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Macular fibrosis	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Macular oedema	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Narrow anterior chamber angle	1/313 (0.3%)	2	0/313 (0%)	0	0/311 (0%)	0
Ocular hypertension	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Retinal artery occlusion	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Retinal haemorrhage	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Retinal neovascularisation	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Retinal tear	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Rhegmatogenous retinal detachment	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Uveitic glaucoma	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Uveitis	0/313 (0%)	0	4/313 (1.3%)	4	0/311 (0%)	0
Visual acuity reduced	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Vitreous haemorrhage	3/313 (1%)	3	1/313 (0.3%)	1	1/311 (0.3%)	1
Gastrointestinal disorders
Abdominal hernia	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Colitis	1/313 (0.3%)	2	0/313 (0%)	0	0/311 (0%)	0
Constipation	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Diabetic gastroparesis	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Gastrointestinal haemorrhage	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Gastrooesophageal reflux disease	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Large intestine polyp	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Nausea	1/313 (0.3%)	1	0/313 (0%)	0	1/311 (0.3%)	1
Oesophagitis	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Pancreatitis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Vomiting	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
General disorders
Chest pain	2/313 (0.6%)	2	0/313 (0%)	0	3/311 (1%)	3
Death	1/313 (0.3%)	1	3/313 (1%)	3	0/311 (0%)	0
Fatigue	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
General physical health deterioration	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Generalised oedema	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Ill-defined disorder	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Oedema peripheral	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Pyrexia	1/313 (0.3%)	1	1/313 (0.3%)	1	0/311 (0%)	0
Hepatobiliary disorders
Biliary dyskinesia	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Cholecystitis acute	1/313 (0.3%)	1	1/313 (0.3%)	1	0/311 (0%)	0
Cholecystitis chronic	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Cholelithiasis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Chronic hepatitis	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Hepatic cirrhosis	1/313 (0.3%)	2	0/313 (0%)	0	1/311 (0.3%)	1
Non-alcoholic steatohepatitis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Infections and infestations
Abscess limb	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Anal abscess	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	2
Bacteraemia	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Bronchitis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
COVID-19	0/313 (0%)	0	3/313 (1%)	3	0/311 (0%)	0
Cellulitis	3/313 (1%)	3	4/313 (1.3%)	4	2/311 (0.6%)	2
Cellulitis gangrenous	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Cholecystitis infective	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Chorioretinitis	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Clostridium difficile colitis	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Complicated appendicitis	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Diabetic foot infection	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Diabetic gangrene	1/313 (0.3%)	1	1/313 (0.3%)	1	0/311 (0%)	0
Endophthalmitis	0/313 (0%)	0	3/313 (1%)	3	0/311 (0%)	0
Erysipelas	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Fungal infection	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Gastroenteritis norovirus	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Infected bite	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Keratouveitis	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Kidney infection	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Localised infection	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Osteomyelitis	3/313 (1%)	3	1/313 (0.3%)	1	3/311 (1%)	3
Pneumonia	4/313 (1.3%)	5	3/313 (1%)	3	5/311 (1.6%)	5
Pneumonia bacterial	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Pneumonia escherichia	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Pseudomonal sepsis	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Pyelonephritis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Sepsis	4/313 (1.3%)	4	0/313 (0%)	0	6/311 (1.9%)	6
Sepsis syndrome	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Sinusitis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Staphylococcal infection	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Urinary tract infection	2/313 (0.6%)	3	0/313 (0%)	0	1/311 (0.3%)	1
Urosepsis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Viral keratouveitis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Injury, poisoning and procedural complications
Cataract traumatic	1/313 (0.3%)	1	1/313 (0.3%)	1	0/311 (0%)	0
Corneal abrasion	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Fall	1/313 (0.3%)	1	1/313 (0.3%)	1	0/311 (0%)	0
Femoral neck fracture	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Femur fracture	1/313 (0.3%)	1	1/313 (0.3%)	1	0/311 (0%)	0
Head injury	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Hip fracture	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Ilium fracture	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Limb injury	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Radius fracture	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Rib fracture	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Spinal compression fracture	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Thermal burn	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Tibia fracture	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Upper limb fracture	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Wound dehiscence	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Investigations
Blood creatinine increased	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Blood potassium increased	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Blood testosterone increased	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Influenza A virus test positive	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Diabetes mellitus	2/313 (0.6%)	2	0/313 (0%)	0	0/311 (0%)	0
Diabetic complication	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Diabetic ketoacidosis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Diabetic metabolic decompensation	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Hyperglycaemia	2/313 (0.6%)	3	0/313 (0%)	0	1/311 (0.3%)	1
Hyperkalaemia	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Hypoglycaemia	0/313 (0%)	0	2/313 (0.6%)	3	0/311 (0%)	0
Hypokalaemia	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Hyponatraemia	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Lactic acidosis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Back pain	0/313 (0%)	0	1/313 (0.3%)	2	0/311 (0%)	0
Bursitis	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Intervertebral disc protrusion	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Muscle spasms	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Muscular weakness	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Myalgia	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Neck pain	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Neuropathic arthropathy	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Osteoarthritis	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Osteochondrosis	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Spinal osteoarthritis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	0/313 (0%)	0	1/313 (0.3%)	1	2/311 (0.6%)	2
Bile duct cancer	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Bladder cancer	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Breast cancer	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Leukaemia	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Neoplasm	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Pancreatic carcinoma	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Plasma cell myeloma	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Renal neoplasm	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Tumour invasion	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Nervous system disorders
Cerebral haemorrhage	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Cerebral infarction	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Cerebrovascular accident	2/313 (0.6%)	2	3/313 (1%)	3	1/311 (0.3%)	1
Coma	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Dizziness	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Epilepsy	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Haemorrhagic stroke	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Hypertensive encephalopathy	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Hypoxic-ischaemic encephalopathy	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Ischaemic stroke	3/313 (1%)	3	0/313 (0%)	0	1/311 (0.3%)	2
Lumbar radiculopathy	0/313 (0%)	0	1/313 (0.3%)	1	1/311 (0.3%)	1
Presyncope	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Syncope	2/313 (0.6%)	3	1/313 (0.3%)	1	0/311 (0%)	0
Transient ischaemic attack	1/313 (0.3%)	1	1/313 (0.3%)	1	0/311 (0%)	0
Vertigo CNS origin	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Product Issues
Device dislocation	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Psychiatric disorders
Completed suicide	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Delusional disorder, unspecified type	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Depression	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Disorientation	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Mental status changes	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Renal and urinary disorders
Acute kidney injury	4/313 (1.3%)	4	1/313 (0.3%)	1	3/311 (1%)	3
Chronic kidney disease	1/313 (0.3%)	1	0/313 (0%)	0	3/311 (1%)	3
End stage renal disease	2/313 (0.6%)	2	0/313 (0%)	0	2/311 (0.6%)	2
Hydronephrosis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Renal failure	2/313 (0.6%)	3	1/313 (0.3%)	1	1/311 (0.3%)	1
Renal impairment	1/313 (0.3%)	1	0/313 (0%)	0	1/311 (0.3%)	1
Urinary retention	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Reproductive system and breast disorders
Ovarian cyst	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/313 (0.6%)	2	0/313 (0%)	0	2/311 (0.6%)	2
Apnoea	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Chronic obstructive pulmonary disease	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Dyspnoea exertional	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Hypoxia	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Pleural effusion	1/313 (0.3%)	1	1/313 (0.3%)	1	0/311 (0%)	0
Pneumonia aspiration	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Pulmonary embolism	2/313 (0.6%)	2	0/313 (0%)	0	1/311 (0.3%)	1
Respiratory failure	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Skin and subcutaneous tissue disorders
Diabetic foot	0/313 (0%)	0	1/313 (0.3%)	1	3/311 (1%)	3
Surgical and medical procedures
Cholecystectomy	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Vascular disorders
Aneurysm	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Aortic stenosis	1/313 (0.3%)	1	1/313 (0.3%)	1	0/311 (0%)	0
Arteriosclerosis	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Blood pressure inadequately controlled	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Deep vein thrombosis	0/313 (0%)	0	0/313 (0%)	0	1/311 (0.3%)	1
Embolism	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Hypertension	1/313 (0.3%)	1	1/313 (0.3%)	1	3/311 (1%)	4
Peripheral artery thrombosis	1/313 (0.3%)	1	0/313 (0%)	0	0/311 (0%)	0
Varicose vein	0/313 (0%)	0	1/313 (0.3%)	1	0/311 (0%)	0
Other (Not Including Serious) Adverse Events
	A: Faricimab 6 mg Q8W		B: Faricimab 6 mg PTI		C: Aflibercept 2 mg Q8W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	86/313 (27.5%)		100/313 (31.9%)		100/311 (32.2%)
Eye disorders
Cataract	21/313 (6.7%)	27	19/313 (6.1%)	22	21/311 (6.8%)	33
Conjunctival haemorrhage	24/313 (7.7%)	30	28/313 (8.9%)	36	23/311 (7.4%)	30
Diabetic retinal oedema	12/313 (3.8%)	15	18/313 (5.8%)	19	19/311 (6.1%)	21
Vitreous detachment	14/313 (4.5%)	18	16/313 (5.1%)	19	12/311 (3.9%)	15
Infections and infestations
Nasopharyngitis	21/313 (6.7%)	24	15/313 (4.8%)	17	22/311 (7.1%)	27
Vascular disorders
Hypertension	16/313 (5.1%)	20	17/313 (5.4%)	18	23/311 (7.4%)	24

Limitations/Caveats

All secondary outcome measures were unpowered for statistical analysis, and the results should be interpreted with caution.

More Information

Certain Agreements

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

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