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

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03622593
• Collaborator: (none)
• Enrollment: 951
• Locations: 195
• Arms: 3
• Actual Duration (Months): 34.6
• Patients Per Site: 4.9
• 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: 951 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 (RHINE)
• Actual Study Start Date: Oct 9, 2018
• Actual Primary Completion Date: Oct 19, 2020
• Actual Study Completion Date: Aug 27, 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 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 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 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 (DRS) Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) 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 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	Retinal Research Institute, LLC	Phoenix	Arizona	United States	85014
2	Associated Retina Consultants	Phoenix	Arizona	United States	85020
3	Northwest Arkansas Retina Associates	Springdale	Arkansas	United States	72762
4	California Retina Consultants	Bakersfield	California	United States	93309
5	Retina-Vitreous Associates Medical Group	Beverly Hills	California	United States	90211
6	The Retina Partners	Encino	California	United States	91436
7	Retina Consultants of Orange County	Fullerton	California	United States	92835
8	Northern California Retina Vitreous Associates	Mountain View	California	United States	94040
9	Retinal Consultants Med Group	Sacramento	California	United States	95825
10	California Retina Consultants	Santa Barbara	California	United States	93103
11	Bay Area Retina Associates	Walnut Creek	California	United States	94598
12	University of Colorado; dept of ophthalmology	Aurora	Colorado	United States	80045
13	Retina Consultants of Southern	Colorado Springs	Colorado	United States	80909
14	Retina Group of New England	Waterford	Connecticut	United States	06385
15	Retina Group of Florida	Fort Lauderdale	Florida	United States	33308
16	National Ophthalmic Research Institute	Fort Myers	Florida	United States	33912
17	Florida Eye Associates	Melbourne	Florida	United States	32901
18	Bascom Palmer Eye Institute	Palm Beach Gardens	Florida	United States	33418
19	Fort Lauderdale Eye Institute	Plantation	Florida	United States	33324
20	Retina Vitreous Assoc of FL	Saint Petersburg	Florida	United States	33711
21	Southeast Retina Center	Augusta	Georgia	United States	30909
22	University Retina and Macula Associates, PC	Oak Forest	Illinois	United States	60452
23	Prairie Retina Center	Springfield	Illinois	United States	62704
24	Retina Specialists	Towson	Maryland	United States	21204
25	Tufts Medical Center; Ophthalmology	Boston	Massachusetts	United States	02111
26	Associated Retinal Consultants	Grand Rapids	Michigan	United States	49546
27	Vitreo-Retinal Associates	Grand Rapids	Michigan	United States	49546
28	Retina Consultants of Nevada	Las Vegas	Nevada	United States	89123
29	Envision Ocular, LLC	Bloomfield	New Jersey	United States	07003
30	Mid Atlantic Retina - Wills Eye Hospital	Cherry Hill	New Jersey	United States	08034
31	Long Is. Vitreoretinal Consult	Great Neck	New York	United States	11021
32	New York University	New York	New York	United States	10017
33	Ophthalmic Cons of Long Island	Oceanside	New York	United States	11572
34	Retina Assoc of Western NY	Rochester	New York	United States	14620
35	University of Rochester Flaum Eye Institute	Rochester	New York	United States	14642
36	The Retina Consultants	Slingerlands	New York	United States	12159
37	Cleveland Clinic Foundation; Cole Eye Institute	Cleveland	Ohio	United States	44195
38	Palmetto Retina Center	Florence	South Carolina	United States	29501
39	Retina Consultants Of Carolina	Greenville	South Carolina	United States	29605
40	Charleston Neuroscience Inst	Ladson	South Carolina	United States	29456
41	Southeastern Retina Associates Chattanooga	Chattanooga	Tennessee	United States	37421
42	Southeastern Retina Associates	Knoxville	Tennessee	United States	37923
43	Tennessee Retina PC	Nashville	Tennessee	United States	37203
44	Austin Retina Associates	Austin	Texas	United States	78705
45	Retina Consultants of Texas	Bellaire	Texas	United States	77401
46	Retina Center of Texas	Southlake	Texas	United States	76092
47	Univ of Virginia Ophthalmology	Charlottesville	Virginia	United States	22903
48	Retina Institute of Virginia	Richmond	Virginia	United States	23235
49	Retina Center Northwest	Silverdale	Washington	United States	98383
50	Organizacion Medica de Investigacion	Buenos Aires		Argentina	C1015ABO
51	Fundacion Zambrano	Caba		Argentina	C1017AAO
52	Oftalmos	Capital Federal		Argentina	C1120AAN
53	Oftar	Mendoza		Argentina	M5500GGK
54	Centro Oftalmólogos Especialistas	Rosario		Argentina	S2000ANJ
55	Grupo Laser Vision	Rosario		Argentina	S2000DLA
56	Strathfield Retina Clinic	Strathfield	New South Wales	Australia	2135
57	Sydney Eye Hospital	Sydney	New South Wales	Australia	2000
58	Sydney Retina Clinic and Day Surgery	Sydney	New South Wales	Australia	2000
59	Sydney West Retina	Westmead	New South Wales	Australia	2145
60	Centre For Eye Research Australia	East Melbourne	Victoria	Australia	3002
61	Retina Specialists Victoria	Rowville	Victoria	Australia	3178
62	The Lions Eye Institute	Nedlands	Western Australia	Australia	6009
63	Hospital de Olhos de Aparecida - HOA	Aparecida de Goiania	GO	Brazil	74980-010
64	Centro Brasileiro de Cirurgia	Goiania	GO	Brazil	74210-010
65	Hospital das Clinicas - UFRGS	Porto Alegre	RS	Brazil	90035-903
66	Botelho Hospital da Visao	Blumenau	SC	Brazil	89052-504
67	Faculdade de Medicina do ABC - FMABC	Santo Andre	SP	Brazil	09060-650
68	Universidade Federal de Sao Paulo - UNIFESP*X; Oftalmologia	Sao Paulo	SP	Brazil	04023-062
69	CEMAPE - Centro Médico	Sao Paulo	SP	Brazil	04084-002
70	Hospital das Clinicas - FMUSP	Sao Paulo	SP	Brazil	05403-900
71	Hosp de Olhos de Sorocaba	Sorocaba	SP	Brazil	18031-060
72	Calgary Retina Consultants	Calgary	Alberta	Canada	T2J 0C8
73	University of British Columbia - Vancouver Coastal Health Authority	Vancouver	British Columbia	Canada	V5Z 1M9
74	QEII - HSC Department of Ophthalmology	Halifax	Nova Scotia	Canada	B3H 2Y9
75	Vitreous Retina Macula Specialists of Toronto	Etobicoke	Ontario	Canada	M8X 2X3
76	Ivey Eye Institute	London	Ontario	Canada	N6A 4V2
77	University of Ottawa Eye Institute	Ottawa	Ontario	Canada	K1H 8L6
78	Toronto Retina Institute	Toronto	Ontario	Canada	M3C 0G9
79	Unity Health Toronto	Toronto	Ontario	Canada	M5B IW8
80	University Health Network Toronto Western Hospital	Toronto	Ontario	Canada	M5T 2S9
81	Institut De L'Oeil Des Laurentides	Boisbriand	Quebec	Canada	J7H 0E8
82	Hôpital Maisonneuve - Rosemont	Montreal	Quebec	Canada	H1T 2M4
83	Peking Union Medical College Hospital	Beijing City		China	100032
84	Beijing Friendship Hospital	Beijing		China	100050
85	Beijing Tongren Hospital	Beijing		China	100730
86	The Second Hospital of Jilin University	Changchun		China	130041
87	West China Hospital, Sichuan University	Chengdu		China	610041
88	Southwest Hospital , Third Military Medical University; Ophthalmology	Chongqing City		China	400014
89	Third Affiliated Hospital of Third Military Medical University; Ophthalmology	ChongQing		China	400000
90	Zhongshan Ophthalmic Center, Sun Yat-sen University	Guangzhou City		China	510060
91	The Affiliated Eye Hospital of Nanjing Medical University	Nanjing City		China	210029
92	Shanghai Tenth People's Hospital	Shanghai		China	200072
93	Shanghai First People's Hospital	Shanghai		China	200080
94	Tianjin Eye Hospital	Tianjin City		China	300050
95	Tianjin Medical University Eye Hospital	Tianjin City		China	300070
96	Eye Hospital, Wenzhou Medical University	Wenzhou City		China	325027
97	Wuxi No.2 People's Hospital	Wuxi		China	214000
98	FN Hradec Králové, Oční klinika; Ophthalmology clinic	Hradec Králové		Czechia	500 05
99	Faculty Hospital Ostrava; Ophthalmology clinic	Ostrava		Czechia	708 52
100	Faculty Hospital Kralovske Vinohrady; Ophthalmology clinic	Prague		Czechia	100 34
101	AXON Clinical	Prague		Czechia
102	Nemocnice Sokolov	Sokolov		Czechia	356 01
103	Aalborg Universitetshospital; Øjenafdelingen	Aalborg		Denmark	9000
104	Rigshospitalet Glostrup; Afdeling for Øjensygdomme, Center for Forskning	Glostrup		Denmark	2600
105	Sjællands Universitetshospital, Roskilde; Øjenafdelingen	Roskilde		Denmark	4000
106	Chi De Creteil; Ophtalmologie	Creteil		France	94010
107	CHU Bocage; Ophtalmologie	Dijon		France	21079
108	Hopital de la croix rousse; Ophtalmologie	Lyon cedex		France	69317
109	CHNO des Quinze Vingts; Ophtalmologie	Paris		France	75012
110	Centre Ophtalmologique; Imagerie et laser	Paris		France	75015
111	Centres Ophtalmologique St Exupéry; Ophtalmologie	St Cyr Sur Loire		France	37540
112	Hôpital PURPAN - CHU TOULOUSE; Ophtalmologie	Toulouse		France	31059
113	Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Augenheilkunde	Dresden		Germany	01307
114	Universitätsklinikum Freiburg, Klinik für Augenheilkunde	Freiburg		Germany	79106
115	Universitätsklinikum des Saarlandes; Klinik für Augenheilkunde	Homburg/Saar		Germany	66424
116	Universitätsklinikum Magdeburg A.ö.R., Universitätsaugenklinik	Magdeburg		Germany	39120
117	LMU Klinikum der Universität, Augenklinik	München		Germany	80336
118	Klinikum rechts der Isar der TU München; Augenklinik	München		Germany	81675
119	Universitätsklinikum Würzburg, Augenklinik und Poliklinik	Würzburg		Germany	97080
120	Queen Mary Hospital; Department of Ophthalmology	Hong Kong		Hong Kong	999077
121	Hong Kong Eye Hospital; CUHK Eye Centre	Mongkok		Hong Kong
122	Magyar Honvedseg Egeszsegugyi Kozpont; Szemészeti Osztály	Budapest		Hungary	1068
123	Peterfy Sandor utcai Korhaz-Rendelointezet es Baleseti Kozpont, Szemeszet KR	Budapest		Hungary	1076
124	Semmelweis Egyetem Szemészeti Vizsgálóhely	Budapest		Hungary	1085
125	Bajcsy-Zsilinszky Hospital	Budapest		Hungary	1106
126	Fondazione Ptv Policlinico Tor Vergata Di Roma;U.O.S.D. Patologie Renitiche	Roma	Lazio	Italy	00133
127	ASST FATEBENEFRATELLI SACCO; Oculistica (Sacco)	Milano	Lombardia	Italy	20157
128	Azienda Ospedaliero-Universitaria Careggi; S.O.D. Oculistica	Firenze	Toscana	Italy	50134
129	Nuovo Ospedale S. Chiara - A.O.U.P Presidio Ospedaliero di Cisanello; U.O. Oculistica Universitaria	Pisa	Toscana	Italy	56124
130	Ospedale Classificato Equiparato Sacro Cuore - Don Calabria; Dipartimento Oculistica	Negrar - Verona	Veneto	Italy	37024
131	A.O. Universitaria S. Maria Della Misericordia Di Udine; Clinica Oculistica	Udine	Veneto	Italy	33100
132	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13605
133	Kyung Hee University Hospital	Seoul		Korea, Republic of	02447
134	Seoul National University Hospital	Seoul		Korea, Republic of	03080
135	Samsung Medical Center	Seoul		Korea, Republic of	06351
136	Asan Medical Center.	Seoul		Korea, Republic of	138-736
137	OFTALMIKA Sp. z o.o	Bydgoszcz		Poland	85-631
138	Specjalistyczny Ośrodek Okulistyczny Oculomedica	Bydgoszcz		Poland	85-870
139	Optimum Profesorskie Centrum Okulistyki	Gdańsk		Poland	80-809
140	Poradnia Okulistyczna i Salon Optyczny w Gliwicach- PRYZMAT	Gliwice		Poland	44-100
141	SP ZOZ Szpital Uniwersytecki w Krakowie Oddział Kliniczny Okulistyki i Onkologii Okulistycznej	Krakow		Poland	31-501
142	Osrodek Chirurgii Oka prof. Zagorskiego Rzeszow	Rzeszów		Poland	35-017
143	Caminomed	Tarnowskie Góry		Poland	42-600
144	Centrum Zdrowia MDM	Warszawa		Poland	00-631
145	Hospital de Braga; Servico de Oftalmologia	Braga		Portugal	4710-243
146	AIBILI - Association for Innovation and Biomedical Research on Light	Coimbra		Portugal	3000-548
147	Espaco Medico Coimbra	Coimbra		Portugal	3030-163
148	Hospital de Santa Maria; Servico de Oftalmologia	Lisboa		Portugal	1649-035
149	Intersec Research and Technology Complex "Eye Microsurgery" n.a. S.N. Fyodorov; Cheboksary Branch	Cheboksary	Marij EL	Russian Federation	428000
150	Clinics of Eye Diseases, LLC	Kazan	Tatarstan	Russian Federation	420066
151	"Intersec. Research and Technology Complex "Eye Microsurgery" n a Fyodorov Irkutsk branch	Irkutsk		Russian Federation	664033
152	"Intersec Research and Technology Complex Eye Microsurgery n a Fyodorov Novosibirsk Branch	Novosibirsk		Russian Federation	630096
153	National University Hospital; Ophthalmology Department	Singapore		Singapore	119074
154	Singapore Eye Research Institute	Singapore		Singapore	168751
155	Tan Tock Seng Hospital; Ophthalmology Department	Singapore		Singapore	308433
156	Instituto Oftalmologico Fernandez Vega; Servicio de oftalmologia	Oviedo	Asturias	Spain	33012
157	Hospital Universitario de Bellvitge	Hospitalet de Llobregat	Barcelona	Spain	08907
158	Hospital General de Catalunya	San Cugat Del Valles	Barcelona	Spain	08195
159	Complejo Hospitalario de Navarra; Servicio de oftalmologia	Pamplona	Navarra	Spain	31008
160	Oftalvist Valencia	Burjassot	Valencia	Spain	46100
161	Institut de la Macula i la retina	Barcelona		Spain	08022
162	Hospital dos de maig; Pharmacy Service	Barcelona		Spain	08025
163	Hospital Clinico San Carlos; Servicio de oftalmologia	Madrid		Spain	28040
164	Clinica Baviera; Servicio Oftalmologia	Madrid		Spain	28046
165	Fisabio-Ofalmologia Medica; Servicio de Oftalmología	Valencia		Spain	46015
166	Hospital Universitario Rio Hortega; Servicio de Oftalmologia	Valladolid		Spain	47012
167	Vista Klinik Ophthalmologische Klinik	Binningen		Switzerland	4102
168	Taipei Veterans General Hospital; Ophthalmology	Taipei		Taiwan	11217
169	Chang Gung Medical Foundation - Linkou; Ophthalmology	Taoyuan		Taiwan	333
170	National Taiwan University Hospital; Ophthalmology	Zhongzheng Dist.		Taiwan	10002
171	King Chulalongkorn Memorial Hospital; Ophthalmology Department	Bangkok		Thailand	10330
172	Rajavithi Hospital; Ophthalmology Department	Bangkok		Thailand	10400
173	Maharaj Nakorn ChiangMai Hospital; Ophthalmology Department	ChiangMai		Thailand	50200
174	Ankara University Medical Faculty; Department of Ophthalmology	Ankara		Turkey	06340
175	Ankara Baskent University Medical Faculty; Department of Ophthalmology	Ankara		Turkey	06490
176	Beyoglu Goz Training and Research Hospital; Department Of Ophthalmology	Istanbul		Turkey	34421
177	Kocaeli Üniversitesi Tıp Fakültesi; Department of Ophthalmology	Kocaeli		Turkey	41380
178	Barnet Hospital; ROYAL FREE LONDON NHS FOUNDATION TRUST	Barnet		United Kingdom	EN5 3DJ
179	Belfast Health and Social Care Trust, ROYAL VICTORIA HOSPITAL	Belfast		United Kingdom	BT12 6BA
180	Bradford Royal Infirmary	Bradford		United Kingdom	BD9 6RJ
181	University Hospitals Bristol NHS Foundation Trust, Bristol Eye Hospital	Bristol		United Kingdom	BS1 2LX
182	East Kent Hospitals University NHS Foundation Trust	Canterbury		United Kingdom	CT1 3NG
183	Frimley Park Hospital	Frimley		United Kingdom	GU16 7UJ
184	Gloucestershire Hospitals NHS Foundation Trust	Gloucestershire		United Kingdom	GL1 3NN
185	St James University Hospital	Leeds		United Kingdom	LS9 7TF
186	Royal Liverpool University Hospital; St Paul's Clinical Eye Research Centre	Liverpool		United Kingdom	L7 8XP
187	Moorfields Eye Hospital NHS Foundation Trust	London		United Kingdom	EC1V 2PD
188	Royal Free Hospital	London		United Kingdom	NW3 2QS
189	Kings College Hospital	London		United Kingdom	SW9 8RR
190	Manchester Royal Eye Hospital	Manchester		United Kingdom	M13 9WL
191	Hillingdon Hospital	Middx		United Kingdom	UB8 3NN
192	Royal Victoria Infirmary	Newcastle upon Tyne		United Kingdom	NE1 4LP
193	James Paget University Hospitals NHS Foundation Trust	Norfolk		United Kingdom	NR31 6LA
194	University Hospital Southampton NHS Foundation Trust; Southampton Eye Unit	Southampton		United Kingdom	SO16 6YD
195	Sunderland Eye Infirmary	Sunderland		United Kingdom	SR2 9HP

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: NCT03622593
• Other Study ID Numbers: GR40398; 2017-005105-12
• First Posted: Aug 9, 2018
• Last Update Posted: Apr 6, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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	317	319	315
Received at Least One Dose of Study Drug	317	319	314
Completed up to Week 56	298	312	299
COMPLETED	0	0	0
NOT COMPLETED	317	319	315

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	317	319	315	951
Age (Years) [Mean (Standard Deviation) ]
ITT Population	62.5 (10.1)	61.6 (10.1)	62.3 (10.1)	62.2 (10.1)
Treatment-Naive Population	62.5 (9.9)	61.3 (10.3)	62.5 (10.0)	62.1 (10.0)
Sex: Female, Male (Count of Participants)
Female	123 38.8%	120 37.6%	129 41%	372 39.1%
Male	194 61.2%	199 62.4%	186 59%	579 60.9%
Female	100 31.5%	94 29.5%	97 30.8%	291 30.6%
Male	154 48.6%	161 50.5%	151 47.9%	466 49%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	56 17.7%	78 24.5%	67 21.3%	201 21.1%
Not Hispanic or Latino	252 79.5%	232 72.7%	240 76.2%	724 76.1%
Unknown or Not Reported	9 2.8%	9 2.8%	8 2.5%	26 2.7%
Hispanic or Latino	42 13.2%	57 17.9%	54 17.1%	153 16.1%
Not Hispanic or Latino	204 64.4%	190 59.6%	188 59.7%	582 61.2%
Unknown or Not Reported	8 2.5%	8 2.5%	6 1.9%	22 2.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 0.3%	1 0.1%
Asian	34 10.7%	36 11.3%	32 10.2%	102 10.7%
Native Hawaiian or Other Pacific Islander	2 0.6%	0 0%	0 0%	2 0.2%
Black or African American	18 5.7%	23 7.2%	24 7.6%	65 6.8%
White	250 78.9%	249 78.1%	253 80.3%	752 79.1%
More than one race	2 0.6%	1 0.3%	0 0%	3 0.3%
Unknown or Not Reported	11 3.5%	10 3.1%	5 1.6%	26 2.7%
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	26 8.2%	29 9.1%	25 7.9%	80 8.4%
Native Hawaiian or Other Pacific Islander	2 0.6%	0 0%	0 0%	2 0.2%
Black or African American	16 5%	20 6.3%	17 5.4%	53 5.6%
White	197 62.1%	197 61.8%	201 63.8%	595 62.6%
More than one race	2 0.6%	1 0.3%	0 0%	3 0.3%
Unknown or Not Reported	11 3.5%	8 2.5%	5 1.6%	24 2.5%
Number of Participants by Previous Treatment Status with Intravitreal Anti-VEGF Agents (Count of Participants)
Treatment-Naive	254 80.1%	255 79.9%	248 78.7%	757 79.6%
Previously Treated	63 19.9%	64 20.1%	67 21.3%	194 20.4%
Region of Enrollment (Count of Participants)
United States and Canada	110 34.7%	111 34.8%	109 34.6%	330 34.7%
Asia	29 9.1%	29 9.1%	26 8.3%	84 8.8%
Rest of the World	178 56.2%	179 56.1%	180 57.1%	537 56.5%
United States and Canada	87 27.4%	88 27.6%	84 26.7%	259 27.2%
Asia	23 7.3%	24 7.5%	21 6.7%	68 7.2%
Rest of the World	144 45.4%	143 44.8%	143 45.4%	430 45.2%
Number of Participants by the Eye Chosen as the Study Eye (Left or Right) (Count of Participants)
Left Eye	156 49.2%	168 52.7%	146 46.3%	470 49.4%
Right Eye	161 50.8%	151 47.3%	169 53.7%	481 50.6%
Left Eye	128 40.4%	136 42.6%	117 37.1%	381 40.1%
Right Eye	126 39.7%	119 37.3%	131 41.6%	376 39.5%
Baseline Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye (ETDRS Letters) [Mean (Standard Deviation) ]
ITT Population	61.9 (10.1)	62.5 (9.3)	62.1 (9.4)	62.1 (9.6)
Treatment-Naive Population	62.1 (10.1)	62.8 (9.3)	62.6 (9.2)	62.5 (9.5)
Number of Participants by the Baseline BCVA Letter Score Categories in the Study Eye (Count of Participants)
≤38 Letters	14 4.4%	11 3.4%	9 2.9%	34 3.6%
39 to 63 Letters	128 40.4%	132 41.4%	132 41.9%	392 41.2%
≥64 Letters	174 54.9%	174 54.5%	174 55.2%	522 54.9%
Missing/Invalid BCVA	1 0.3%	2 0.6%	0 0%	3 0.3%
≤38 Letters	10 3.2%	8 2.5%	5 1.6%	23 2.4%
39 to 63 Letters	100 31.5%	103 32.3%	100 31.7%	303 31.9%
≥64 Letters	143 45.1%	142 44.5%	143 45.4%	428 45%
Missing/Invalid BCVA	1 0.3%	2 0.6%	0 0%	3 0.3%
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%	4 1.3%	1 0.3%	7 0.7%
2 - DR Questionable / Microaneurysms Only	3 0.9%	10 3.1%	6 1.9%	19 2%
3 - Mild Non-Proliferative Diabetic Retinopathy (NPDR)	90 28.4%	92 28.8%	94 29.8%	276 29%
4 - Moderate NPDR	88 27.8%	72 22.6%	79 25.1%	239 25.1%
5 - Moderately Severe NPDR	59 18.6%	63 19.7%	54 17.1%	176 18.5%
6 - Severe NPDR	50 15.8%	36 11.3%	51 16.2%	137 14.4%
7 - Mild Proliferative Diabetic Retinopathy (PDR)	12 3.8%	26 8.2%	11 3.5%	49 5.2%
8 - Moderate PDR	6 1.9%	10 3.1%	6 1.9%	22 2.3%
9 - High Risk PDR (DRS Level 71)	2 0.6%	1 0.3%	3 1%	6 0.6%
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	2 0.6%	5 1.6%	5 1.6%	12 1.3%
Missing	3 0.9%	0 0%	5 1.6%	8 0.8%
1 - Diabetic Retinopathy (DR) Absent	2 0.6%	3 0.9%	1 0.3%	6 0.6%
2 - DR Questionable / Microaneurysms Only	1 0.3%	8 2.5%	6 1.9%	15 1.6%
3 - Mild Non-Proliferative Diabetic Retinopathy (NPDR)	63 19.9%	66 20.7%	71 22.5%	200 21%
4 - Moderate NPDR	74 23.3%	59 18.5%	56 17.8%	189 19.9%
5 - Moderately Severe NPDR	48 15.1%	56 17.6%	43 13.7%	147 15.5%
6 - Severe NPDR	44 13.9%	32 10%	47 14.9%	123 12.9%
7 - Mild Proliferative Diabetic Retinopathy (PDR)	11 3.5%	17 5.3%	7 2.2%	35 3.7%
8 - Moderate PDR	5 1.6%	9 2.8%	5 1.6%	19 2%
9 - High Risk PDR (DRS Level 71)	2 0.6%	1 0.3%	3 1%	6 0.6%
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	1 0.3%	4 1.3%	4 1.3%	9 0.9%
Missing	3 0.9%	0 0%	5 1.6%	8 0.8%
Baseline Central Subfield Thickness in the Study Eye (microns) [Mean (Standard Deviation) ]
ITT Population	466.2 (119.4)	471.3 (127.0)	477.3 (129.4)	471.6 (125.3)
Treatment-Naive Population	464.6 (117.9)	473.0 (130.5)	474.3 (129.5)	470.6 (126.0)

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	317	319	315
ITT Population	11.8	10.8	10.3
Treatment-Naive Population	11.7	11.2	10.5

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	1.5
	Confidence Interval	(2-Sided) 97.5%; -0.1 to 3.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.73
	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	0.5
	Confidence Interval	(2-Sided) 97.5%; -1.1 to 2.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.73
	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	0.1718
	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	1.1
	Confidence Interval	(2-Sided) 97.5%; -0.7 to 3.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.83
	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	0.4602
	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	0.6
	Confidence Interval	(2-Sided) 97.5%; -1.2 to 2.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.82
	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	0.0361
	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	1.5
	Confidence Interval	(2-Sided) 97.5%; -0.1 to 3.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.73
	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	0.4930
	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	0.5
	Confidence Interval	(2-Sided) 97.5%; -1.1 to 2.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.73
	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 (DRS) Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) 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	231	251	238
ITT Population	44.2 13.9%	43.7 13.7%	46.8 14.9%
Treatment-Naive Population	46.9 14.8%	45.7 14.3%	52.3 16.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: Faricimab 6 mg Q8W, C: Aflibercept 2 mg Q8W
	Comments	This analysis 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 Q8W and the active comparator (aflibercept Q8W) arms was greater than -10%, then faricimab Q8W was considered non-inferior to aflibercept.
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) 97.5%; -12.6 to 7.4
	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 analysis 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 PTI and the active comparator (aflibercept Q8W) arms was greater than -10%, then faricimab PTI was considered non-inferior to aflibercept.
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) 97.5%; -13.4 to 6.3
	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 analysis 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	0.3009
	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	-5.4
	Confidence Interval	(2-Sided) 97.5%; -16.9 to 6.1
	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 analysis 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	0.1735
	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	-6.9
	Confidence Interval	(2-Sided) 97.5%; -18.3 to 4.4
	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 analysis 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	0.5757
	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	-2.6
	Confidence Interval	(2-Sided) 97.5%; -12.6 to 7.4
	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 analysis 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	0.4293
	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	-3.5
	Confidence Interval	(2-Sided) 97.5%; -13.4 to 6.3
	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	268	293	279
Gaining ≥15 Letters	33.8 10.7%	28.5 8.9%	30.3 9.6%
Gaining ≥10 Letters	59.3 18.7%	53.0 16.6%	53.9 17.1%
Gaining ≥5 Letters	81.8 25.8%	77.4 24.3%	78.0 24.8%
Gaining ≥0 Letters	92.1 29.1%	91.1 28.6%	91.4 29%

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	3.5
	Confidence Interval	(2-Sided) 95%; -4.0 to 11.1
	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 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	-2.0
	Confidence Interval	(2-Sided) 95%; -9.1 to 5.2
	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 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	5.4
	Confidence Interval	(2-Sided) 95%; -2.5 to 13.4
	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	-1.1
	Confidence Interval	(2-Sided) 95%; -8.9 to 6.8
	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	3.8
	Confidence Interval	(2-Sided) 95%; -2.7 to 10.3
	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	-0.7
	Confidence Interval	(2-Sided) 95%; -7.3 to 5.9
	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	0.7
	Confidence Interval	(2-Sided) 95%; -3.8 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	-0.3
	Confidence Interval	(2-Sided) 95%; -4.9 to 4.2
	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	208	231	213
Gaining ≥15 Letters	32.9 10.4%	29.4 9.2%	32.7 10.4%
Gaining ≥10 Letters	58.3 18.4%	55.5 17.4%	56.1 17.8%
Gaining ≥5 Letters	81.8 25.8%	79.6 25%	80.6 25.6%
Gaining ≥0 Letters	93.2 29.4%	92.2 28.9%	92.0 29.2%

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 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	0.2
	Confidence Interval	(2-Sided) 95%; -8.5 to 8.9
	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%; -11.8 to 4.8
	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 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	2.2
	Confidence Interval	(2-Sided) 95%; -6.9 to 11.4
	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	-0.8
	Confidence Interval	(2-Sided) 95%; -9.8 to 8.1
	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	1.2
	Confidence Interval	(2-Sided) 95%; -6.2 to 8.5
	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	-1.1
	Confidence Interval	(2-Sided) 95%; -8.3 to 6.2
	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	1.2
	Confidence Interval	(2-Sided) 95%; -3.8 to 6.2
	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	0.2
	Confidence Interval	(2-Sided) 95%; -4.8 to 5.2
	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	268	293	279
Avoiding a Loss of ≥15 Letters	98.9 31.2%	98.7 30.9%	98.6 31.3%
Avoiding a Loss of ≥10 Letters	98.1 30.9%	98.0 30.7%	98.2 31.2%
Avoiding a Loss of ≥5 Letters	96.7 30.5%	97.0 30.4%	95.4 30.3%

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 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	0.3
	Confidence Interval	(2-Sided) 95%; -1.6 to 2.1
	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 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	0.0
	Confidence Interval	(2-Sided) 95%; -1.8 to 1.9
	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	-0.1
	Confidence Interval	(2-Sided) 95%; -2.3 to 2.1
	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 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	-0.3
	Confidence Interval	(2-Sided) 95%; -2.4 to 1.9
	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	1.3
	Confidence Interval	(2-Sided) 95%; -1.9 to 4.5
	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	1.6
	Confidence Interval	(2-Sided) 95%; -1.5 to 4.6
	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	208	231	213
Avoiding a Loss of ≥15 Letters	98.5 31.1%	98.7 30.9%	98.6 31.3%
Avoiding a Loss of ≥10 Letters	98.1 30.9%	97.8 30.7%	98.1 31.1%
Avoiding a Loss of ≥5 Letters	97.6 30.8%	97.4 30.5%	96.2 30.5%

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	0.0
	Confidence Interval	(2-Sided) 95%; -2.3 to 2.2
	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 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	0.1
	Confidence Interval	(2-Sided) 95%; -2.0 to 2.2
	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 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	0.0
	Confidence Interval	(2-Sided) 95%; -2.7 to 2.6
	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 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	-0.3
	Confidence Interval	(2-Sided) 95%; -2.9 to 2.3
	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 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	1.3
	Confidence Interval	(2-Sided) 95%; -2.0 to 4.7
	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	1.2
	Confidence Interval	(2-Sided) 95%; -2.1 to 4.4
	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	268	294	279
ITT Population	38.3 12.1%	32.4 10.2%	33.5 10.6%
Treatment-Naive Population	38.1 12%	34.4 10.8%	35.5 11.3%

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 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	4.8
	Confidence Interval	(2-Sided) 95%; -3.1 to 12.7
	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	-1.3
	Confidence Interval	(2-Sided) 95%; -8.8 to 6.2
	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	2.6
	Confidence Interval	(2-Sided) 95%; -6.5 to 11.6
	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	-1.3
	Confidence Interval	(2-Sided) 95%; -10.0 to 7.4
	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	268	293	279
ITT Population	73.2 23.1%	71.6 22.4%	68.5 21.7%
Treatment-Naive Population	73.6 23.2%	74.2 23.3%	72.1 22.9%

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	4.7
	Confidence Interval	(2-Sided) 95%; -2.4 to 11.8
	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	2.8
	Confidence Interval	(2-Sided) 95%; -4.1 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	1.5
	Confidence Interval	(2-Sided) 95%; -6.5 to 9.4
	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	1.7
	Confidence Interval	(2-Sided) 95%; -6.0 to 9.3
	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	268	294	279
ITT Population	0.8 0.3%	0.0 0%	0.7 0.2%
Treatment-Naive Population	1.0 0.3%	0.0 0%	0.5 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	0.1
	Confidence Interval	(2-Sided) 95%; -1.4 to 1.5
	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 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	-0.7
	Confidence Interval	(2-Sided) 95%; -1.6 to 0.2
	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	0.5
	Confidence Interval	(2-Sided) 95%; -1.1 to 2.1
	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	-0.5
	Confidence Interval	(2-Sided) 95%; -1.4 to 0.4
	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	215	221	221
ITT Population	0.8 0.3%	0.9 0.3%	0.4 0.1%
Treatment-Naive Population	0.6 0.2%	1.2 0.4%	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%; -1.0 to 1.8
	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	0.5
	Confidence Interval	(2-Sided) 95%; -1.0 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%; -0.6 to 1.8
	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	1.2
	Confidence Interval	(2-Sided) 95%; -0.4 to 2.8
	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	230	250	236
ITT Population	0.0 0%	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	0.0
	Confidence Interval	(2-Sided) 95%; 0.0 to 0.0
	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	0.0
	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	308
Once Every 4 Weeks	13.3 4.2%
Once Every 8 Weeks	15.6 4.9%
Once Every 12 Weeks	20.1 6.3%
Once Every 16 Weeks	51.0 16.1%

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	245
Once Every 4 Weeks	11.8 3.7%
Once Every 8 Weeks	13.9 4.4%
Once Every 12 Weeks	20.0 6.3%
Once Every 16 Weeks	54.3 17.1%

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	308
ITT Population	64.3 20.3%
Treatment-Naive Population	66.9 21.1%

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	317	319	315
ITT Population	-195.8	-187.6	-170.1
Treatment-Naive Population	-195.0	-189.4	-175.1

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	-25.7
	Confidence Interval	(2-Sided) 95%; -37.4 to -14.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.95
	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	-17.6
	Confidence Interval	(2-Sided) 95%; -29.2 to -6.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.88
	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	-20.0
	Confidence Interval	(2-Sided) 95%; -32.9 to -7.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.59
	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	-14.3
	Confidence Interval	(2-Sided) 95%; -27.1 to -1.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.51
	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	268	294	279
ITT Population	85.5 27%	81.5 25.5%	73.2 23.2%
Treatment-Naive Population	86.0 27.1%	83.2 26.1%	77.0 24.4%

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 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	12.3
	Confidence Interval	(2-Sided) 95%; 5.7 to 18.9
	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	8.2
	Confidence Interval	(2-Sided) 95%; 1.5 to 14.9
	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	9.0
	Confidence Interval	(2-Sided) 95%; 1.6 to 16.3
	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	6.2
	Confidence Interval	(2-Sided) 95%; -1.2 to 13.6
	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	5/317 (1.6%)		0/319 (0%)		5/314 (1.6%)
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	67/317 (21.1%)		49/319 (15.4%)		58/314 (18.5%)
Blood and lymphatic system disorders
Anaemia	1/317 (0.3%)	1	1/319 (0.3%)	1	2/314 (0.6%)	2
Microcytic anaemia	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Cardiac disorders
Acute coronary syndrome	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Acute myocardial infarction	0/317 (0%)	0	1/319 (0.3%)	1	2/314 (0.6%)	2
Angina pectoris	0/317 (0%)	0	1/319 (0.3%)	1	1/314 (0.3%)	1
Angina unstable	1/317 (0.3%)	1	1/319 (0.3%)	2	0/314 (0%)	0
Aortic valve stenosis	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Arteriosclerosis coronary artery	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Atrial fibrillation	1/317 (0.3%)	1	1/319 (0.3%)	1	0/314 (0%)	0
Cardiac arrest	2/317 (0.6%)	2	1/319 (0.3%)	1	0/314 (0%)	0
Cardiac failure	1/317 (0.3%)	1	1/319 (0.3%)	1	3/314 (1%)	4
Cardiac failure acute	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Cardiac failure chronic	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Cardiac failure congestive	4/317 (1.3%)	4	2/319 (0.6%)	2	1/314 (0.3%)	1
Coronary artery disease	1/317 (0.3%)	1	1/319 (0.3%)	1	1/314 (0.3%)	1
Ischaemic cardiomyopathy	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Myocardial infarction	3/317 (0.9%)	3	1/319 (0.3%)	1	2/314 (0.6%)	2
Myocardial ischaemia	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Right ventricular failure	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Subendocardial ischaemia	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Ear and labyrinth disorders
Tinnitus	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Eye disorders
Cataract	2/317 (0.6%)	2	0/319 (0%)	0	1/314 (0.3%)	1
Cataract subcapsular	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Diabetic retinal oedema	5/317 (1.6%)	7	2/319 (0.6%)	2	0/314 (0%)	0
Diabetic retinopathy	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Dry eye	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Eye haemorrhage	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Macular fibrosis	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Ocular hypertension	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Retinal neovascularisation	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Retinal tear	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Retinal vein occlusion	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Visual acuity reduced	0/317 (0%)	0	1/319 (0.3%)	1	1/314 (0.3%)	1
Visual acuity reduced transiently	1/317 (0.3%)	1	1/319 (0.3%)	1	1/314 (0.3%)	1
Visual impairment	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Vitreous haemorrhage	4/317 (1.3%)	4	1/319 (0.3%)	1	1/314 (0.3%)	1
Gastrointestinal disorders
Colitis	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Gastrointestinal dysplasia	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Gastrointestinal haemorrhage	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Impaired gastric emptying	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Rectal haemorrhage	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Upper gastrointestinal haemorrhage	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
General disorders
Chest pain	0/317 (0%)	0	1/319 (0.3%)	1	1/314 (0.3%)	1
Inflammation	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Malaise	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Multiple organ dysfunction syndrome	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Necrosis	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Pyrexia	0/317 (0%)	0	0/319 (0%)	0	3/314 (1%)	3
Soft tissue inflammation	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Hepatobiliary disorders
Bile duct stenosis	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Cholecystitis	0/317 (0%)	0	1/319 (0.3%)	1	1/314 (0.3%)	1
Cholelithiasis	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Immune system disorders
Anaphylactic reaction	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Hypersensitivity	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Infections and infestations
Abscess limb	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Anal abscess	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Arthritis bacterial	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
COVID-19 pneumonia	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Cellulitis	3/317 (0.9%)	4	1/319 (0.3%)	1	7/314 (2.2%)	7
Cellulitis gangrenous	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Cystitis	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Diabetic foot infection	3/317 (0.9%)	3	0/319 (0%)	0	0/314 (0%)	0
Diabetic gangrene	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	2
Diverticulitis	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Endocarditis	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Endophthalmitis	2/317 (0.6%)	2	0/319 (0%)	0	1/314 (0.3%)	1
Escherichia sepsis	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Gallbladder empyema	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Gangrene	1/317 (0.3%)	1	2/319 (0.6%)	2	0/314 (0%)	0
Gastroenteritis	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Influenza	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Osteomyelitis	2/317 (0.6%)	2	1/319 (0.3%)	1	3/314 (1%)	4
Pneumonia	5/317 (1.6%)	5	4/319 (1.3%)	4	3/314 (1%)	3
Pyelonephritis	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Respiratory tract infection	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Sepsis	5/317 (1.6%)	5	0/319 (0%)	0	1/314 (0.3%)	1
Upper respiratory tract infection	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Urinary tract infection	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Injury, poisoning and procedural complications
Chemical burns of eye	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	2
Corneal abrasion	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Fall	0/317 (0%)	0	1/319 (0.3%)	1	1/314 (0.3%)	1
Femoral neck fracture	1/317 (0.3%)	1	1/319 (0.3%)	1	2/314 (0.6%)	2
Femur fracture	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Fracture displacement	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Limb injury	1/317 (0.3%)	1	1/319 (0.3%)	1	0/314 (0%)	0
Nail avulsion	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Pelvic fracture	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Investigations
Blood glucose fluctuation	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Intraocular pressure increased	1/317 (0.3%)	1	1/319 (0.3%)	1	0/314 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/317 (0.3%)	1	0/319 (0%)	0	1/314 (0.3%)	1
Diabetic endorgan damage	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Diabetic ketoacidosis	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	7
Gout	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Hyperkalaemia	0/317 (0%)	0	1/319 (0.3%)	1	1/314 (0.3%)	1
Hypoglycaemia	1/317 (0.3%)	1	3/319 (0.9%)	3	0/314 (0%)	0
Type 1 diabetes mellitus	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Musculoskeletal and connective tissue disorders
Neuropathic arthropathy	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Spondylitis	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Bladder cancer	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Colon cancer	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Hairy cell leukaemia	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Lung neoplasm malignant	1/317 (0.3%)	2	0/319 (0%)	0	0/314 (0%)	0
Pancreatic carcinoma	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Nervous system disorders
Cauda equina syndrome	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Cerebral haemorrhage	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Cerebral infarction	1/317 (0.3%)	1	1/319 (0.3%)	1	0/314 (0%)	0
Cerebrovascular accident	1/317 (0.3%)	1	1/319 (0.3%)	1	1/314 (0.3%)	1
Cervical radiculopathy	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	2
Guillain-Barre syndrome	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Lacunar stroke	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Metabolic encephalopathy	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Spinal cord compression	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Syncope	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Transient ischaemic attack	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Psychiatric disorders
Delirium	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Depression	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Renal and urinary disorders
Acute kidney injury	2/317 (0.6%)	2	2/319 (0.6%)	2	1/314 (0.3%)	1
Azotaemia	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Calculus urinary	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Chronic kidney disease	1/317 (0.3%)	1	0/319 (0%)	0	1/314 (0.3%)	1
Diabetic nephropathy	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
End stage renal disease	2/317 (0.6%)	2	1/319 (0.3%)	1	0/314 (0%)	0
Renal cyst	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Renal failure	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Urinary tract inflammation	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/317 (0%)	0	1/319 (0.3%)	1	1/314 (0.3%)	1
Dyspnoea	2/317 (0.6%)	2	1/319 (0.3%)	1	0/314 (0%)	0
Lung disorder	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Pleural effusion	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Pulmonary fibrosis	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Pulmonary oedema	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Respiratory arrest	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Respiratory failure	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (0%)	0
Skin and subcutaneous tissue disorders
Diabetic foot	0/317 (0%)	0	2/319 (0.6%)	2	1/314 (0.3%)	1
Vascular disorders
Arterial occlusive disease	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Deep vein thrombosis	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Extremity necrosis	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Hypertension	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Hypertensive crisis	0/317 (0%)	0	1/319 (0.3%)	1	0/314 (0%)	0
Hypertensive urgency	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	1
Hypotension	0/317 (0%)	0	2/319 (0.6%)	2	1/314 (0.3%)	1
Orthostatic hypotension	0/317 (0%)	0	0/319 (0%)	0	1/314 (0.3%)	2
Peripheral arterial occlusive disease	1/317 (0.3%)	2	0/319 (0%)	0	0/314 (0%)	0
Peripheral vascular disorder	1/317 (0.3%)	1	0/319 (0%)	0	0/314 (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	116/317 (36.6%)		98/319 (30.7%)		116/314 (36.9%)
Eye disorders
Cataract	26/317 (8.2%)	36	17/319 (5.3%)	26	15/314 (4.8%)	24
Conjunctival haemorrhage	30/317 (9.5%)	38	20/319 (6.3%)	23	22/314 (7%)	31
Diabetic retinal oedema	24/317 (7.6%)	25	19/319 (6%)	23	16/314 (5.1%)	18
Vitreous detachment	15/317 (4.7%)	20	10/319 (3.1%)	11	19/314 (6.1%)	22
Infections and infestations
Nasopharyngitis	23/317 (7.3%)	25	22/319 (6.9%)	27	31/314 (9.9%)	35
Urinary tract infection	7/317 (2.2%)	10	11/319 (3.4%)	12	20/314 (6.4%)	23
Nervous system disorders
Headache	16/317 (5%)	26	9/319 (2.8%)	11	5/314 (1.6%)	6
Vascular disorders
Hypertension	15/317 (4.7%)	15	19/319 (6%)	19	11/314 (3.5%)	11

Limitations/Caveats

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

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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.