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A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Neovascular Age-Related Macular Degeneration (LUCERNE)

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT03823300
Collaborator
(none)
658
Enrollment
139
Locations
2
Arms
33.9
Actual Duration (Months)
4.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy, safety, durability, and pharmacokinetics of faricimab administered at intervals as specified in the protocol, compared with aflibercept once every 8 weeks (Q8W), in participants with neovascular age-related macular degeneration (nAMD).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
658 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 in Patients With Neovascular Age-Related Macular Degeneration (LUCERNE)
Actual Study Start Date :
Mar 11, 2019
Actual Primary Completion Date :
Oct 5, 2020
Actual Study Completion Date :
Jan 7, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A: Faricimab

Drug: Faricimab
Faricimab will be administered by intravitreal injection into the study eye at intervals as specified in the study protocol.
Other Names:
  • VABYSMO™
  • RO6867461
  • RG7716

    • Procedure: Sham Procedure
    The sham is a procedure that mimics an intravitreal injection, but involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. It will be administered to participants in both treatment arms at applicable visits to maintain masking.
    Active Comparator: Arm B: Aflibercept

    Drug: Aflibercept
    Aflibercept will be administered by intravitreal injection into the study eye once every 4 weeks for 3 consecutive months, followed by once every 8 weeks (Q8W).
    Other Names:
  • Eylea

    • Procedure: Sham Procedure
    The sham is a procedure that mimics an intravitreal injection, but involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. It will be administered to participants in both treatment arms at applicable visits to maintain masking.

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 40, 44, and 48 [From Baseline through Week 48]

      Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (≥74, 73-55, and ≤54 letters), baseline LLD (<33 and ≥33 letters), and region (U.S. and Canada, Asia, and rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after 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% CI is a rounding of 95.03% CI.

    Secondary Outcome Measures

    1. Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 52, 56, and 60 [From Baseline through Week 60]

      Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (≥74, 73-55, and ≤54 letters), baseline LLD (<33 and ≥33 letters), and region (U.S. and Canada, Asia, and rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after 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% CI is a rounding of 95.03% CI.

    2. Change From Baseline in BCVA in the Study Eye Over Time [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, 100, 104, 108, and 112]

      Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (≥74, 73-55, and ≤54 letters), baseline LLD (<33 and ≥33 letters), and region (U.S. and Canada, Asia, and rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after 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% CI is a rounding of 95.03% CI.

    3. Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 40, 44, and 48 [Baseline, average of Weeks 40, 44, and 48]

      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 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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    4. Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 52, 56, and 60 [Baseline, average of Weeks 52, 56, and 60]

      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 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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    5. Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA in the Study Eye Over Time [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, 100, 104, 108, and 112]

      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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    6. Percentage of Participants Gaining ≥10 Letters From the Baseline BCVA in the Study Eye Over Time [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, 100, 104, 108, and 112]

      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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    7. Percentage of Participants Gaining ≥5 Letters From the Baseline BCVA in the Study Eye Over Time [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, 100, 104, 108, and 112]

      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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    8. Percentage of Participants Gaining ≥0 Letters From the Baseline BCVA in the Study Eye Over Time [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, 100, 104, 108, and 112]

      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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    9. Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 40, 44, and 48 [Baseline, average of Weeks 40, 44, and 48]

      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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    10. Percentage of Participants Avoiding a Loss of ≥15 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 52, 56, and 60 [Baseline, average of Weeks 52, 56, and 60]

      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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    11. Percentage of Participants Avoiding a Loss of ≥15 Letters From the Baseline BCVA in the Study Eye Over Time [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, 100, 104, 108, and 112]

      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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    12. Percentage of Participants Avoiding a Loss of ≥10 Letters From the Baseline BCVA in the Study Eye Over Time [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, 100, 104, 108, and 112]

      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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    13. Percentage of Participants Avoiding a Loss of ≥5 Letters From the Baseline BCVA in the Study Eye Over Time [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, 100, 104, 108, and 112]

      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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    14. Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 40, 44, and 48 [Baseline, average of Weeks 40, 44, and 48]

      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 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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    15. Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time [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, 100, 104, 108, and 112]

      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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    16. Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 40, 44, and 48 [Baseline, average of Weeks 40, 44, and 48]

      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 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 letters vs. ≥69 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    17. Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time [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, 100, 104, 108, and 112]

      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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (<69 letters vs. ≥69 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    18. Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 40, 44, and 48 [Average of Weeks 40, 44, and 48]

      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 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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    19. Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time [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, 100, 104, 108, and 112]

      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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.

    20. Percentage of Participants in the Faricimab Arm on Once Every 8-Weeks, 12-Weeks, or 16-Weeks Treatment Intervals at Week 48 [Week 48]

    21. Percentage of Participants in the Faricimab Arm on Once Every 8-Weeks, 12-Weeks, or 16-Weeks Treatment Intervals at Weeks 60 and 112 [Weeks 60 and 112]

    22. Number of Study Drug Injections Received in the Study Eye Per Participant Through Week 48 [From Baseline through Week 48]

    23. Number of Study Drug Injections Received in the Study Eye Per Participant Through Weeks 60 and 112 [From Baseline through Weeks 60 and 112]

    24. Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 40, 44, and 48 [From Baseline through Week 48]

      Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group iteraction, baseline CST (continuous), baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (<33 letters and ≥33 letters), and region (U.S. and Canada, Asia, and the rest of the world). 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 95.03% CI.

    25. Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 52, 56, and 60 [From Baseline through Week 60]

      Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (<33 letters and ≥33 letters), and region (U.S. and Canada, Asia, and the rest of the world). 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 95.03% CI.

    26. Change From Baseline in Central Subfield Thickness in the Study Eye Over Time [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, 100, 104, 108, and 112]

      Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (<33 letters and ≥33 letters), and region (U.S. and Canada, Asia, and the rest of the world). 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 95.03% CI.

    27. Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112]

      Intraretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 millimetre [mm]). The weighted estimates of the percentage of participants with absence of intraretinal fluid were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 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 95.03% CI.

    28. Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112]

      Subretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants with absence of intraretinal fluid were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 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 95.03% CI.

    29. Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112]

      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 with absence of intraretinal fluid were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 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 95.03% CI.

    30. Percentage of Participants With Absence of Pigment Epithelial Detachment in the Study Eye Over Time [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112]

      Pigment epithelial detachment was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants with absence of pigment epithelial detachment were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 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 95.03% CI.

    31. Percentage of Participants With Absence of Intraretinal Cysts in the Study Eye Over Time [Up to 112 weeks]

    32. Change From Baseline in Total Area of Choroidal Neovascularization Lesion in the Study Eye at Week 48 [Baseline and Week 48]

      The total area of the choroidal neovascularization lesion in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.

    33. Change From Baseline in Total Area of Choroidal Neovascularization Lesion in the Study Eye at Week 112 [Baseline and Week 112]

      The total area of the choroidal neovascularization lesion in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.

    34. Change From Baseline in Total Area of Choroidal Neovascularization Leakage in the Study Eye at Week 48 [Baseline and Week 48]

      The total area of choroidal neovascularization leakage in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.

    35. Change From Baseline in Total Area of Choroidal Neovascularization Leakage in the Study Eye at Week 112 [Baseline and Week 112]

      The total area of choroidal neovascularization leakage in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.

    36. Percentage of Participants With Ocular Adverse Events During the Study [Up to 116 weeks]

    37. Percentage of Participants With Non-Ocular Adverse Events During the Study [Up to 116 weeks]

    38. Plasma Concentration of Faricimab Over Time [Pre-dose at Baseline, Weeks 4, 16, 20, 48, 76, and 112]

    39. Percentage of Participants With Presence of Anti-Drug Antibodies to Faricimab at Baseline and at Anytime Post-Baseline [Pre-dose at Baseline, Weeks 4, 20, 48, 76, and 112]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Treatment-naïve choroidal neovascularization (CNV) secondary to age-related macular degeneration (nAMD) in the study eye

    • Ability to comply with the study protocol, in the investigator's judgment

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

    • Other protocol-specified inclusion criteria may apply

    Exclusion Criteria:

    • Uncontrolled blood pressure, defined as systolic blood pressure >180 millimeters of mercury (mmHg) and/or diastolic blood pressure >100 mmHg while a patient is at rest on Day 1

    • Pregnancy or breastfeeding, or intention to become pregnant during the study

    • CNV due to causes other than AMD in the study eye

    • Any history of macular pathology unrelated to AMD affecting vision or contributing to the presence of intraretinal or subretinal fluid in the study eye

    • Any concurrent intraocular condition in the study eye that, in the opinion of the investigator, could either reduce the potential for visual improvement or require medical or surgical intervention during the study

    • Uncontrolled glaucoma in the study eye

    • Any prior or concomitant treatment for CNV or vitreomacular-interface abnormalities in the study eye

    • Prior IVT administration of faricimab in either eye

    • History of idiopathic or autoimmune-associated uveitis in either eye

    • Active ocular inflammation or suspected or active ocular or periocular infection in either eye

    • Other protocol-specified exclusion criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Associated Retina Consultants Phoenix Arizona United States 85020
    2 Arizona Retina and Vitreous Consultants Phoenix Arizona United States 85021
    3 Northern California Retina Vitreous Associates Mountain View California United States 94040
    4 Retinal Consultants Med Group Sacramento California United States 95825
    5 Orange County Retina Med Group Santa Ana California United States 92705
    6 California Retina Consultants Santa Barbara California United States 93103
    7 Colorado Retina Associates, PC Lakewood Colorado United States 80228
    8 Retina Group of Florida Fort Lauderdale Florida United States 33308
    9 Retina Care Specialists Palm Beach Gardens Florida United States 33410
    10 Southern Vitreoretinal Assoc Tallahassee Florida United States 32308
    11 Retina Associates of Florida, LLC Tampa Florida United States 33609
    12 Southeast Retina Center Augusta Georgia United States 30909
    13 Georgia Retina PC Marietta Georgia United States 30060
    14 Retina Consultants of Hawaii 'Aiea Hawaii United States 96701
    15 University Retina and Macula Associates, PC Lemont Illinois United States 60439
    16 Prairie Retina Center Springfield Illinois United States 62704
    17 Raj K. Maturi, MD PC Indianapolis Indiana United States 46290
    18 Wolfe Eye Clinic West Des Moines Iowa United States 50266
    19 Maine Eye Center Portland Maine United States 04101
    20 The Retina Care Center Baltimore Maryland United States 21209
    21 Cumberland Valley Retina PC Hagerstown Maryland United States 21740
    22 Retina Specialists Towson Maryland United States 21204
    23 Ophthalmic Consultants of Boston Boston Massachusetts United States 02114
    24 VitreoRetinal Surgery, PLLC.; DBA Retina Consultants of Minnesota Edina Minnesota United States 55435
    25 Mid Atlantic Retina - Wills Eye Hospital Cherry Hill New Jersey United States 08034
    26 Island Retina Shirley New York United States 11967
    27 Retina Assoc of Cleveland Inc Cleveland Ohio United States 44122
    28 The Ohio State University Havener Eye Institute Columbus Ohio United States 43212
    29 Midwest Retina Dublin Ohio United States 43016
    30 Palmetto Retina Center Florence South Carolina United States 29501
    31 Southeastern Retina Associates Chattanooga Chattanooga Tennessee United States 37421
    32 Retina Res Institute of Texas Abilene Texas United States 79606
    33 Austin Retina Associates Austin Texas United States 78705
    34 Austin Clinical Research LLC Austin Texas United States 78750
    35 Retina Specialists DeSoto Texas United States 75115
    36 Retina Center of Texas Southlake Texas United States 76092
    37 Retina Consultants of Houston The Woodlands Texas United States 77384
    38 Strategic Clinical Research Group, LLC Willow Park Texas United States 76087
    39 Retina Associates of Utah Salt Lake City Utah United States 84107
    40 Piedmont Eye Center Lynchburg Virginia United States 24502
    41 Wagner Macula & Retina Center Norfolk Virginia United States 23502
    42 Retina Center Northwest Silverdale Washington United States 98383
    43 Organizacion Medica de Investigacion Buenos Aires Argentina C1015ABO
    44 Fundacion Zambrano Caba Argentina C1017AAO
    45 Centro Oftalmológico Dr. Charles S.A. Capital Federal Argentina C1015ABO
    46 Oftalmos Capital Federal Argentina C1120AAN
    47 Buenos Aires Mácula Ciudad Autonoma Buenos Aires Argentina C1061AAE
    48 Oftar Mendoza Argentina M5500GGK
    49 Grupo Laser Vision Rosario Argentina S2000DLA
    50 Eyeclinic Albury Wodonga Albury New South Wales Australia 2640
    51 Marsden Eye Research Centre Parramatta New South Wales Australia 2150
    52 Strathfield Retina Clinic Strathfield New South Wales Australia 2135
    53 Sydney Eye Hospital Sydney New South Wales Australia 2000
    54 Sydney Retina Clinic and Day Surgery Sydney New South Wales Australia 2000
    55 Sydney West Retina Westmead New South Wales Australia 2145
    56 Centre For Eye Research Australia East Melbourne Victoria Australia 3002
    57 Retina Specialists Victoria Rowville Victoria Australia 3178
    58 The Lions Eye Institute Nedlands Western Australia Australia 6009
    59 LKH-Univ.Klinikum Graz; Universitäts-Augenklinik Graz Austria 8036
    60 Medizinische Universität Wien; Universitätsklinik für Augenheilkunde und Optometrie Wien Austria 1090
    61 Hospital de Olhos de Aparecida - HOA Aparecida de Goiania GO Brazil 74980-010
    62 Universidade Federal de Sao Paulo - UNIFESP*X; Oftalmologia Sao Paulo SP Brazil 04023-062
    63 Pentagram Eye Hospital (Medical Center "Pentagram") Sofia Bulgaria 1309
    64 Specialized Hospital for Active Treatment of Eye Diseases Zora Sofia Bulgaria 1784
    65 Peking Union Medical College Hospital Beijing City China 100032
    66 Beijing Friendship Hospital Beijing China 100050
    67 Beijing Tongren Hospital Beijing China 100730
    68 The Second Hospital of Jilin University; ophthalmology department Changchun City China 130041
    69 West China Hospital, Sichuan University Chengdu China 610041
    70 Southwest Hospital , Third Military Medical University; Ophthalmology Chongqing City China 400014
    71 Daping Hospital of Third Military Medical University Chongqing China 400042
    72 Zhongshan Ophthalmic Center, Sun Yat-sen University Guangzhou City China 510060
    73 The Second Affiliated Hospital of Harbin Medical University; ophthalmology department Harbin China 150081
    74 The Affiliated Eye Hospital of Nanjing Medical University Nanjing City China 210029
    75 Shanghai First People's Hospital Shanghai China 200080
    76 He Eye Specialist Shenyang Hospital Shenyang City China 110034
    77 Tianjin Eye Hospital Tianjin City China 300050
    78 Eye Hospital, Wenzhou Medical University Wenzhou City China 325027
    79 Wuxi No.2 People's Hospital Wuxi China 214000
    80 Rigshospitalet Glostrup; Afdeling for Øjensygdomme, Center for Forskning Glostrup Denmark 2600
    81 Sjællands Universitetshospital, Roskilde; Øjenafdelingen Roskilde Denmark 4000
    82 Chi De Creteil; Ophtalmologie Creteil France 94010
    83 Pole Vision Val d'Ouest; Ophtalmologie Ecully France 69130
    84 Hopital de la croix rousse; Ophtalmologie Lyon cedex France 69317
    85 Centre Paradis Monticelli; Ophtalmologie Marseille France 13008
    86 CHU Nantes - Hôtel Dieu; Ophthalmology Nantes France 44093
    87 Centre Odeon; Exploration Ophtalmologique Paris France 75006
    88 Hopital Lariboisiere; Ophtalmologie Paris France 75010
    89 Centre Ophtalmologique; Imagerie et laser Paris France 75015
    90 Centres Ophtalmologique St Exupéry; Ophtalmologie St Cyr Sur Loire France 37540
    91 Universitätkslinikum Düsseldorf, Augenklinik; Klinik fürAugenheilkunde Düsseldorf Germany 40225
    92 Universitätsklinikum Köln; Augenklinik Köln Germany 50937
    93 Augenabteilung am St. Franziskus-Hospital Münster Germany 48145
    94 Universitätsklinikum Münster; Augenheilkunde Münster Germany 48149
    95 Queen Mary Hospital; Department of Ophthalmology Hong Kong Hong Kong
    96 Hong Kong Eye Hospital; CUHK Eye Centre Mongkok Hong Kong
    97 Magyar Honvedseg Egeszsegugyi Kozpont; Szemészeti Osztály Budapest Hungary 1068
    98 Bajcsy-Zsilinszky Hospital Budapest Hungary 1106
    99 Szegedi Tudományegyetem ÁOK; Department of Ophtalmology Szeged Hungary 6720
    100 Fondazione Ptv Policlinico Tor Vergata Di Roma;U.O.S.D. Patologie Renitiche Roma Lazio Italy 00133
    101 UNIVERSITA' DEGLI STUDI DI GENOVA - Di.N.O.G.;CLINICA OCULISTICA Genova Liguria Italy 16132
    102 ASST FATEBENEFRATELLI SACCO; Oculistica (Sacco) Milano Lombardia Italy 20157
    103 Azienda Ospedaliero-Universitaria Careggi; S.O.D. Oculistica Firenze Toscana Italy 50134
    104 Nuovo Ospedale S. Chiara - A.O.U.P Presidio Ospedaliero di Cisanello; U.O. Oculistica Universitaria Pisa Toscana Italy 56124
    105 A.O. Universitaria S. Maria Della Misericordia Di Udine; Clinica Oculistica Udine Veneto Italy 33100
    106 Pusan National University Hospital Busan Korea, Republic of 49241
    107 Yeungnam University Medical Center Daegu Korea, Republic of 42415
    108 Seoul National University Bundang Hospital Seongnam-si Korea, Republic of 13605
    109 Kyung Hee University Hospital Seoul Korea, Republic of 02447
    110 Seoul National University Hospital Seoul Korea, Republic of 03080
    111 Nune Eye Hospital; Ophthalmology Seoul Korea, Republic of 06192
    112 Samsung Medical Center Seoul Korea, Republic of 06351
    113 Asan Medical Center. Seoul Korea, Republic of 138-736
    114 OFTALMIKA Sp. z o.o Bydgoszcz Poland 85-631
    115 Optimum Profesorskie Centrum Okulistyki Gdańsk Poland 80-809
    116 SP ZOZ Szpital Uniwersytecki w Krakowie Oddział Kliniczny Okulistyki i Onkologii Okulistycznej Krakow Poland 31-501
    117 Caminomed Tarnowskie Góry Poland 42-600
    118 Hospital de Braga; Servico de Oftalmologia Braga Portugal 4710-243
    119 Centro Hospitalar E Universitário de Coimbra EPE - Serviço Oftalmologia; Serviço Oftalmologia Coimbra Portugal 3000-075
    120 Hospital de Sao Joao; Servico de Oftalmologia Porto Portugal 4200-319
    121 Intersec Research and Technology Complex "Eye Microsurgery" n.a. S.N. Fyodorov; Cheboksary Branch Cheboksary Marij EL Russian Federation 428000
    122 "Intersec. Research and Technology Complex "Eye Microsurgery" n a Fyodorov Irkutsk branch Irkutsk Russian Federation 664033
    123 "Intersec Research and Technology Complex Eye Microsurgery n a Fyodorov Novosibirsk Branch Novosibirsk Russian Federation 630096
    124 1 Saint-Petersburg St. Med. University named after academician I.P.Pavlov; Chair of ophathalmology Saint Petersburg Russian Federation 197022
    125 National University Hospital; Ophthalmology Department Singapore Singapore 119074
    126 Singapore Eye Research Institute Singapore Singapore 168751
    127 Instituto Oftalmologico Fernandez Vega; Servicio de oftalmologia Oviedo Asturias Spain 33012
    128 Hospital Universitario de Bellvitge Hospitalet de Llobregat Barcelona Spain 08907
    129 Institut de la Macula i la retina Barcelona Spain 08022
    130 Hospital Clinic de Barcelona; Consultas Externas Oftalmologia Barcelona Spain 08028
    131 Hospital Universitario Rio Hortega; Servicio de Oftalmologia Valladolid Spain 47012
    132 Hospital Universitario Miguel Servet; Servicio de Oftalmologia Zaragoza Spain 50009
    133 Changhua Christian Hospital; Department of Ophthalmology Changhua Taiwan 500
    134 Taipei Veterans General Hospital; Ophthalmology Taipei Taiwan 11217
    135 Chang Gung Medical Foundation - Linkou; Ophthalmology Taoyuan Taiwan 333
    136 Hacettepe University Medical Faculty; Department of Ophthalmology Ankara Turkey 06100
    137 Ankara University Medical Faculty; Department of Ophthalmology Ankara Turkey 06340
    138 Gazi University Faculty of Medicine; Department Of Ophthalmology Ankara Turkey 06560
    139 Ege University Medical Faculty; Department of Ophthalmology Izmir Turkey 35100

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT03823300
    Other Study ID Numbers:
    • GR40844
    • 2018-004042-42
    First Posted:
    Jan 30, 2019
    Last Update Posted:
    Aug 1, 2022
    Last Verified:
    Jul 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
    Keywords provided by Hoffmann-La Roche
    AMD
    nAMD
    neovascular age-related macular degeneration
    choroidal neovascularization secondary to age-related macular degeneration
    Additional relevant MeSH terms:
    Macular Degeneration
    Wet Macular Degeneration
    Aflibercept

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Period Title: Overall Study
    STARTED 331 327
    Received at Least One Dose of Study Drug 331 326
    Completed up to Week 48 321 309
    COMPLETED 0 0
    NOT COMPLETED 331 327

    Baseline Characteristics

    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept Total
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104). Total of all reporting groups
    Overall Participants 331 327 658
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    74.8
    (8.4)
    76.1
    (8.6)
    75.5
    (8.5)
    Sex: Female, Male (Count of Participants)
    Female
    203
    61.3%
    188
    57.5%
    391
    59.4%
    Male
    128
    38.7%
    139
    42.5%
    267
    40.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    35
    10.6%
    46
    14.1%
    81
    12.3%
    Not Hispanic or Latino
    287
    86.7%
    274
    83.8%
    561
    85.3%
    Unknown or Not Reported
    9
    2.7%
    7
    2.1%
    16
    2.4%
    Race/Ethnicity, Customized (Count of Participants)
    White
    278
    84%
    270
    82.6%
    548
    83.3%
    Asian
    38
    11.5%
    34
    10.4%
    72
    10.9%
    Unknown
    12
    3.6%
    17
    5.2%
    29
    4.4%
    Black or African American
    2
    0.6%
    5
    1.5%
    7
    1.1%
    American Indian or Alaska Native
    1
    0.3%
    0
    0%
    1
    0.2%
    Multiple
    0
    0%
    1
    0.3%
    1
    0.2%
    Region of Enrollment (Count of Participants)
    United States and Canada
    135
    40.8%
    132
    40.4%
    267
    40.6%
    Asia
    35
    10.6%
    33
    10.1%
    68
    10.3%
    Rest of the World
    161
    48.6%
    162
    49.5%
    323
    49.1%
    Number of Participants by the Eye (Right or Left) Chosen as the Study Eye (Count of Participants)
    Right Eye
    168
    50.8%
    170
    52%
    338
    51.4%
    Left Eye
    163
    49.2%
    157
    48%
    320
    48.6%
    Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye (ETDRS Letters) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [ETDRS Letters]
    58.7
    (14.0)
    58.9
    (13.3)
    58.8
    (13.6)
    Number of Participants by the BCVA Letter Score Categories in the Study Eye (Count of Participants)
    ≥74 Letters
    45
    13.6%
    39
    11.9%
    84
    12.8%
    73 to 55 Letters
    181
    54.7%
    183
    56%
    364
    55.3%
    ≤54 Letters
    105
    31.7%
    105
    32.1%
    210
    31.9%
    Number of Participants by the Low Luminance Deficit (LLD) Letter Score Categories in the Study Eye (Count of Participants)
    <33 Letters
    238
    71.9%
    234
    71.6%
    472
    71.7%
    ≥33 Letters
    89
    26.9%
    93
    28.4%
    182
    27.7%
    Missing/Invalid
    4
    1.2%
    0
    0%
    4
    0.6%
    Choroidal Neovascularization (CNV) Lesion Type in the Study Eye by Fundus Fluorescein Angiography (Count of Participants)
    Occult
    171
    51.7%
    140
    42.8%
    311
    47.3%
    Classic
    98
    29.6%
    109
    33.3%
    207
    31.5%
    Minimally Classic
    30
    9.1%
    31
    9.5%
    61
    9.3%
    Retinal Angiomatous Proliferation (RAP)
    14
    4.2%
    15
    4.6%
    29
    4.4%
    Predominantly Classic
    6
    1.8%
    16
    4.9%
    22
    3.3%
    Polypoidal Choroidal Vasculopathy (PCV)
    5
    1.5%
    8
    2.4%
    13
    2%
    Missing
    7
    2.1%
    8
    2.4%
    15
    2.3%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 40, 44, and 48
    Description Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (≥74, 73-55, and ≤54 letters), baseline LLD (<33 and ≥33 letters), and region (U.S. and Canada, Asia, and rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after 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% CI is a rounding of 95.03% CI.
    Time Frame From Baseline through Week 48

    Outcome Measure Data

    Analysis Population Description
    ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 331 327
    Mean (95% Confidence Interval) [ETDRS Letters]
    6.6
    6.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments A sample size of approximately 320 participants in each arm provided greater than 90% power to show non-inferiority of faricimab to aflibercept in the change from baseline BCVA averaged over Weeks 40, 44, and 48 in the ITT population, using a non-inferiority margin of 4 letters at the one-sided 0.02485 significance level.
    Type of Statistical Test Non-Inferiority
    Comments If the lower bound of a two-sided 95.03% confidence interval (CI) for the difference in adjusted means of the two treatments (faricimab minus aflibercept) is greater than -4 letters (the non-inferiority margin), then faricimab is considered non-inferior to aflibercept.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted mean difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -1.7 to 1.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.91
    Estimation Comments The adjusted mean difference was calculated as Arm A: Faricimab minus Arm B: Aflibercept.
    2. Secondary Outcome
    Title Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 52, 56, and 60
    Description Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (≥74, 73-55, and ≤54 letters), baseline LLD (<33 and ≥33 letters), and region (U.S. and Canada, Asia, and rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after 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% CI is a rounding of 95.03% CI.
    Time Frame From Baseline through Week 60

    Outcome Measure Data

    Analysis Population Description
    ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 331 327
    Mean (95% Confidence Interval) [ETDRS Letters]
    6.6
    7.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments
    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 -0.6
    Confidence Interval (2-Sided) 95%
    -2.4 to 1.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.93
    Estimation Comments The adjusted mean difference was calculated as Arm A: Faricimab minus Arm B: Aflibercept.
    3. Secondary Outcome
    Title Change From Baseline in BCVA in the Study Eye Over Time
    Description Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (≥74, 73-55, and ≤54 letters), baseline LLD (<33 and ≥33 letters), and region (U.S. and Canada, Asia, and rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after 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% CI is a rounding of 95.03% 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, 100, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    4. Secondary Outcome
    Title Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 40, 44, and 48
    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 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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.
    Time Frame Baseline, average of Weeks 40, 44, and 48

    Outcome Measure Data

    Analysis Population Description
    ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Participants with at least one non-missing, valid assessment at Weeks 40, 44, or 48 were included in this analysis.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 302 291
    Gaining ≥15 Letters
    20.2
    6.1%
    22.2
    6.8%
    Gaining ≥10 Letters
    39.2
    11.8%
    35.8
    10.9%
    Gaining ≥5 Letters
    60.5
    18.3%
    59.4
    18.2%
    Gaining ≥0 Letters
    82.2
    24.8%
    79.1
    24.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments This is the difference in percentage of participants gaining ≥15 letters in Arm A: Faricimab minus Arm B: Aflibercept.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in CMH Weighted Percentage
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -8.3 to 4.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments This is the difference in percentage of participants gaining ≥10 letters in Arm A: Faricimab minus Arm B: Aflibercept.
    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 3.4
    Confidence Interval (2-Sided) 95%
    -3.9 to 10.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments This is the difference in percentage of participants gaining ≥5 letters in Arm A: Faricimab minus Arm B: Aflibercept.
    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 1.0
    Confidence Interval (2-Sided) 95%
    -6.6 to 8.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments This is the difference in percentage of participants gaining ≥0 letters in Arm A: Faricimab minus Arm B: Aflibercept.
    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 3.1
    Confidence Interval (2-Sided) 95%
    -3.1 to 9.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 52, 56, and 60
    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 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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.
    Time Frame Baseline, average of Weeks 52, 56, and 60

    Outcome Measure Data

    Analysis Population Description
    ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Participants with at least one non-missing, valid assessment at Weeks 52, 56, or 60 were included in this analysis.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 289 276
    Number (95% Confidence Interval) [Percentage of participants]
    22.6
    6.8%
    23.7
    7.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments
    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%
    -7.7 to 5.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference in CMH weighted percentage of participants was calculated as Arm A: Faricimab minus Arm B: Aflibercept.
    6. Secondary Outcome
    Title Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA in the Study Eye Over Time
    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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% 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, 100, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Secondary Outcome
    Title Percentage of Participants Gaining ≥10 Letters From the Baseline BCVA in the Study Eye Over Time
    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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% 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, 100, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Secondary Outcome
    Title Percentage of Participants Gaining ≥5 Letters From the Baseline BCVA in the Study Eye Over Time
    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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% 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, 100, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    9. Secondary Outcome
    Title Percentage of Participants Gaining ≥0 Letters From the Baseline BCVA in the Study Eye Over Time
    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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% 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, 100, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    10. Secondary Outcome
    Title Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 40, 44, and 48
    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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.
    Time Frame Baseline, average of Weeks 40, 44, and 48

    Outcome Measure Data

    Analysis Population Description
    ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Participants with at least one non-missing, valid assessment at Weeks 40, 44, or 48 were included in this analysis.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 302 291
    Avoiding a Loss of ≥15 Letters
    95.8
    28.9%
    97.3
    29.8%
    Avoiding a Loss of ≥10 Letters
    93.8
    28.3%
    94.6
    28.9%
    Avoiding a Loss of ≥5 Letters
    91.2
    27.6%
    88.5
    27.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments This is the difference in the percentage of participants avoiding a loss of ≥15 letters in Arm A: Faricimab minus Arm B: Aflibercept.
    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%
    -4.4 to 1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments This is the difference in the percentage of participants avoiding a loss of ≥10 letters in Arm A: Faricimab minus Arm B: Aflibercept.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in CMH Weighted Percentage
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -4.5 to 2.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments This is the difference in the percentage of participants avoiding a loss of ≥5 letters in Arm A: Faricimab minus Arm B: Aflibercept.
    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%
    -2.1 to 7.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Percentage of Participants Avoiding a Loss of ≥15 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 52, 56, and 60
    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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.
    Time Frame Baseline, average of Weeks 52, 56, and 60

    Outcome Measure Data

    Analysis Population Description
    ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Participants with at least one non-missing, valid assessment at Weeks 52, 56, or 60 were included in this analysis.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 289 276
    Number (95% Confidence Interval) [Percentage of participants]
    96.5
    29.2%
    96.1
    29.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in CMH Weighted Percentage
    Estimated Value 0.4
    Confidence Interval (2-Sided) 95%
    -2.6 to 3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference in CMH weighted percentage of participants was calculated as Arm A: Faricimab minus Arm B: Aflibercept.
    12. Secondary Outcome
    Title Percentage of Participants Avoiding a Loss of ≥15 Letters From the Baseline BCVA in the Study Eye Over Time
    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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% 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, 100, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    13. Secondary Outcome
    Title Percentage of Participants Avoiding a Loss of ≥10 Letters From the Baseline BCVA in the Study Eye Over Time
    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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% 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, 100, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    14. Secondary Outcome
    Title Percentage of Participants Avoiding a Loss of ≥5 Letters From the Baseline BCVA in the Study Eye Over Time
    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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% 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, 100, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    15. Secondary Outcome
    Title Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 40, 44, and 48
    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 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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.
    Time Frame Baseline, average of Weeks 40, 44, and 48

    Outcome Measure Data

    Analysis Population Description
    ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Participants with at least one non-missing, valid assessment at Weeks 40, 44, or 48 were included in this analysis.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 302 291
    Number (95% Confidence Interval) [Percentage of participants]
    24.5
    7.4%
    26.2
    8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments
    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%
    -8.5 to 5.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference in CMH weighted percentage of participants was calculated as Arm A: Faricimab minus Arm B: Aflibercept.
    16. Secondary Outcome
    Title Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time
    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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% 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, 100, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    17. 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 40, 44, and 48
    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 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 letters vs. ≥69 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.
    Time Frame Baseline, average of Weeks 40, 44, and 48

    Outcome Measure Data

    Analysis Population Description
    ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Participants with at least one non-missing, valid assessment at Weeks 40, 44, or 48 were included in this analysis.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 302 291
    Number (95% Confidence Interval) [Percentage of participants]
    55.2
    16.7%
    49.4
    15.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments
    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 5.7
    Confidence Interval (2-Sided) 95%
    -1.4 to 12.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference in CMH weighted percentage of participants was calculated as Arm A: Faricimab minus Arm B: Aflibercept.
    18. Secondary Outcome
    Title Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time
    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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (<69 letters vs. ≥69 letters), baseline LLD (≥33 letters and <33 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 95.03% 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, 100, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    19. 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 40, 44, and 48
    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 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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% CI.
    Time Frame Average of Weeks 40, 44, and 48

    Outcome Measure Data

    Analysis Population Description
    ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Participants with at least one non-missing, valid assessment at Weeks 40, 44, or 48 were included in this analysis.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 302 291
    Number (95% Confidence Interval) [Percentage of participants]
    7.9
    2.4%
    7.5
    2.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments
    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%
    -3.6 to 4.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference in CMH weighted percentage of participants was calculated as Arm A: Faricimab minus Arm B: Aflibercept.
    20. Secondary Outcome
    Title Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time
    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 percentage of participants was based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 95.03% 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, 100, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    21. Secondary Outcome
    Title Percentage of Participants in the Faricimab Arm on Once Every 8-Weeks, 12-Weeks, or 16-Weeks Treatment Intervals at Week 48
    Description
    Time Frame Week 48

    Outcome Measure Data

    Analysis Population Description
    The analysis included all participants randomized to the faricimab arm who completed their Week 48 visit.
    Arm/Group Title Arm A: Faricimab
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).
    Measure Participants 316
    Once Every 8 Weeks
    22.2
    6.7%
    Once Every 12 Weeks
    32.9
    9.9%
    Once Every 16 Weeks
    44.9
    13.6%
    22. Secondary Outcome
    Title Percentage of Participants in the Faricimab Arm on Once Every 8-Weeks, 12-Weeks, or 16-Weeks Treatment Intervals at Weeks 60 and 112
    Description
    Time Frame Weeks 60 and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    23. Secondary Outcome
    Title Number of Study Drug Injections Received in the Study Eye Per Participant Through Week 48
    Description
    Time Frame From Baseline through Week 48

    Outcome Measure Data

    Analysis Population Description
    ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 331 327
    Median (Inter-Quartile Range) [Injections per participant]
    7.0
    8.0
    24. Secondary Outcome
    Title Number of Study Drug Injections Received in the Study Eye Per Participant Through Weeks 60 and 112
    Description
    Time Frame From Baseline through Weeks 60 and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    25. Secondary Outcome
    Title Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 40, 44, and 48
    Description Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group iteraction, baseline CST (continuous), baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (<33 letters and ≥33 letters), and region (U.S. and Canada, Asia, and the rest of the world). 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 95.03% CI.
    Time Frame From Baseline through Week 48

    Outcome Measure Data

    Analysis Population Description
    ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 331 327
    Mean (95% Confidence Interval) [microns]
    -137.1
    -130.8
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments
    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 -6.4
    Confidence Interval (2-Sided) 95%
    -14.8 to 2.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.30
    Estimation Comments The adjusted mean difference was calculated as Arm A: Faricimab minus Arm B: Aflibercept.
    26. Secondary Outcome
    Title Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 52, 56, and 60
    Description Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (<33 letters and ≥33 letters), and region (U.S. and Canada, Asia, and the rest of the world). 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 95.03% CI.
    Time Frame From Baseline through Week 60

    Outcome Measure Data

    Analysis Population Description
    ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 331 327
    Mean (95% Confidence Interval) [microns]
    -135.7
    -137.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A: Faricimab, Arm B: Aflibercept
    Comments
    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 1.4
    Confidence Interval (2-Sided) 95%
    -6.6 to 9.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.05
    Estimation Comments The adjusted mean difference was calculated as Arm A: Faricimab minus Arm B: Aflibercept.
    27. Secondary Outcome
    Title Change From Baseline in Central Subfield Thickness in the Study Eye Over Time
    Description Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (<33 letters and ≥33 letters), and region (U.S. and Canada, Asia, and the rest of the world). 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 95.03% 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, 100, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    28. Secondary Outcome
    Title Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time
    Description Intraretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 millimetre [mm]). The weighted estimates of the percentage of participants with absence of intraretinal fluid were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 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 95.03% CI.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    29. Secondary Outcome
    Title Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time
    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 with absence of intraretinal fluid were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 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 95.03% CI.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    30. Secondary Outcome
    Title Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time
    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 with absence of intraretinal fluid were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 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 95.03% CI.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    31. Secondary Outcome
    Title Percentage of Participants With Absence of Pigment Epithelial Detachment in the Study Eye Over Time
    Description Pigment epithelial detachment was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants with absence of pigment epithelial detachment were based on the Cochran-Mantel Haenszel (CMH) test stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 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 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 95.03% CI.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    32. Secondary Outcome
    Title Percentage of Participants With Absence of Intraretinal Cysts in the Study Eye Over Time
    Description
    Time Frame Up to 112 weeks

    Outcome Measure Data

    Analysis Population Description
    The percentage of participants with absence of intraretinal cysts over time was planned but it was not evaluated (i.e., 0 participants analyzed) because the absence of intraretinal fluid and the absence of intraretinal cysts are described by the same variable during reading center grading.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 0 0
    33. Secondary Outcome
    Title Change From Baseline in Total Area of Choroidal Neovascularization Lesion in the Study Eye at Week 48
    Description The total area of the choroidal neovascularization lesion in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.
    Time Frame Baseline and Week 48

    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 non-missing, valid assessments at Baseline and Week 48 were included in this analysis.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 240 236
    Mean (Standard Deviation) [millimetres squared (mm^2)]
    0.3
    (4.6)
    1.1
    (4.4)
    34. Secondary Outcome
    Title Change From Baseline in Total Area of Choroidal Neovascularization Lesion in the Study Eye at Week 112
    Description The total area of the choroidal neovascularization lesion in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.
    Time Frame Baseline and Week 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    35. Secondary Outcome
    Title Change From Baseline in Total Area of Choroidal Neovascularization Leakage in the Study Eye at Week 48
    Description The total area of choroidal neovascularization leakage in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.
    Time Frame Baseline and Week 48

    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 non-missing, valid assessments at Baseline and Week 48 were included in this analysis.
    Arm/Group Title Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    Measure Participants 241 238
    Mean (Standard Deviation) [millimetres squared (mm^2)]
    -3.3
    (6.6)
    -2.1
    (6.3)
    36. Secondary Outcome
    Title Change From Baseline in Total Area of Choroidal Neovascularization Leakage in the Study Eye at Week 112
    Description The total area of choroidal neovascularization leakage in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.
    Time Frame Baseline and Week 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    37. Secondary Outcome
    Title Percentage of Participants With Ocular Adverse Events During the Study
    Description
    Time Frame Up to 116 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    38. Secondary Outcome
    Title Percentage of Participants With Non-Ocular Adverse Events During the Study
    Description
    Time Frame Up to 116 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    39. Secondary Outcome
    Title Plasma Concentration of Faricimab Over Time
    Description
    Time Frame Pre-dose at Baseline, Weeks 4, 16, 20, 48, 76, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    40. Secondary Outcome
    Title Percentage of Participants With Presence of Anti-Drug Antibodies to Faricimab at Baseline and at Anytime Post-Baseline
    Description
    Time Frame Pre-dose at Baseline, Weeks 4, 20, 48, 76, and 112

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame From randomization until Week 48 (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 Arm A: Faricimab Arm B: Aflibercept
    Arm/Group Description Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W). Participants randomized to the active comparator (Arm B), a 2 mg dose of aflibercept was administered intravitreally (IVT) Q8W after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period. This will consist of three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
    All Cause Mortality
    Arm A: Faricimab Arm B: Aflibercept
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/331 (1.2%) 7/326 (2.1%)
    Serious Adverse Events
    Arm A: Faricimab Arm B: Aflibercept
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 49/331 (14.8%) 57/326 (17.5%)
    Blood and lymphatic system disorders
    Anaemia 1/331 (0.3%) 1 1/326 (0.3%) 1
    Iron deficiency anaemia 0/331 (0%) 0 1/326 (0.3%) 1
    Pancytopenia 0/331 (0%) 0 1/326 (0.3%) 1
    Cardiac disorders
    Acute myocardial infarction 1/331 (0.3%) 1 0/326 (0%) 0
    Angina pectoris 1/331 (0.3%) 1 1/326 (0.3%) 3
    Atrial fibrillation 1/331 (0.3%) 1 2/326 (0.6%) 2
    Cardiac failure 1/331 (0.3%) 1 3/326 (0.9%) 4
    Cardiac failure congestive 2/331 (0.6%) 2 4/326 (1.2%) 9
    Cardiopulmonary failure 0/331 (0%) 0 1/326 (0.3%) 1
    Congestive cardiomyopathy 0/331 (0%) 0 1/326 (0.3%) 1
    Coronary artery disease 1/331 (0.3%) 1 1/326 (0.3%) 1
    Dressler's syndrome 1/331 (0.3%) 1 0/326 (0%) 0
    Myocardial infarction 0/331 (0%) 0 1/326 (0.3%) 1
    Myocardial ischaemia 1/331 (0.3%) 1 0/326 (0%) 0
    Palpitations 1/331 (0.3%) 1 0/326 (0%) 0
    Paroxysmal atrioventricular block 0/331 (0%) 0 1/326 (0.3%) 1
    Pericardial effusion 1/331 (0.3%) 1 0/326 (0%) 0
    Pericarditis 1/331 (0.3%) 1 0/326 (0%) 0
    Ventricular extrasystoles 1/331 (0.3%) 1 0/326 (0%) 0
    Ventricular fibrillation 1/331 (0.3%) 1 0/326 (0%) 0
    Ear and labyrinth disorders
    Vertigo 0/331 (0%) 0 1/326 (0.3%) 1
    Eye disorders
    Angle closure glaucoma 1/331 (0.3%) 1 0/326 (0%) 0
    Cataract 1/331 (0.3%) 1 0/326 (0%) 0
    Cataract cortical 0/331 (0%) 0 1/326 (0.3%) 1
    Corneal oedema 0/331 (0%) 0 1/326 (0.3%) 1
    Eye allergy 0/331 (0%) 0 1/326 (0.3%) 1
    Macular degeneration 1/331 (0.3%) 1 0/326 (0%) 0
    Neovascular age-related macular degeneration 4/331 (1.2%) 4 0/326 (0%) 0
    Retinal haemorrhage 0/331 (0%) 0 1/326 (0.3%) 1
    Retinal pigment epithelial tear 2/331 (0.6%) 2 0/326 (0%) 0
    Retinal vein occlusion 1/331 (0.3%) 1 0/326 (0%) 0
    Uveitis 1/331 (0.3%) 1 1/326 (0.3%) 1
    Vitreous haemorrhage 1/331 (0.3%) 1 1/326 (0.3%) 1
    Vitritis 2/331 (0.6%) 2 0/326 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 0/331 (0%) 0 1/326 (0.3%) 1
    Ascites 0/331 (0%) 0 1/326 (0.3%) 3
    Constipation 0/331 (0%) 0 3/326 (0.9%) 4
    Diarrhoea 0/331 (0%) 0 1/326 (0.3%) 1
    Diverticulum intestinal 0/331 (0%) 0 1/326 (0.3%) 1
    Gastritis 0/331 (0%) 0 1/326 (0.3%) 1
    Gastrointestinal haemorrhage 0/331 (0%) 0 1/326 (0.3%) 1
    Upper gastrointestinal haemorrhage 0/331 (0%) 0 1/326 (0.3%) 1
    General disorders
    Adverse drug reaction 1/331 (0.3%) 1 0/326 (0%) 0
    Death 0/331 (0%) 0 1/326 (0.3%) 1
    Ill-defined disorder 1/331 (0.3%) 1 0/326 (0%) 0
    Pain 0/331 (0%) 0 1/326 (0.3%) 1
    Hepatobiliary disorders
    Biliary obstruction 0/331 (0%) 0 1/326 (0.3%) 1
    Cholecystitis 0/331 (0%) 0 1/326 (0.3%) 1
    Cholecystitis acute 0/331 (0%) 0 1/326 (0.3%) 1
    Infections and infestations
    Bronchitis 0/331 (0%) 0 1/326 (0.3%) 1
    COVID-19 3/331 (0.9%) 3 1/326 (0.3%) 1
    Cellulitis 0/331 (0%) 0 2/326 (0.6%) 2
    Chorioretinitis 1/331 (0.3%) 1 0/326 (0%) 0
    Diverticulitis 0/331 (0%) 0 1/326 (0.3%) 1
    Endophthalmitis 0/331 (0%) 0 2/326 (0.6%) 2
    Infectious pleural effusion 0/331 (0%) 0 1/326 (0.3%) 1
    Infective exacerbation of chronic obstructive airways disease 0/331 (0%) 0 1/326 (0.3%) 2
    Influenza 0/331 (0%) 0 1/326 (0.3%) 1
    Necrotising fasciitis 0/331 (0%) 0 1/326 (0.3%) 1
    Osteomyelitis 1/331 (0.3%) 1 1/326 (0.3%) 1
    Pneumonia 1/331 (0.3%) 1 2/326 (0.6%) 2
    Pyelonephritis acute 0/331 (0%) 0 1/326 (0.3%) 1
    Sepsis 0/331 (0%) 0 2/326 (0.6%) 2
    Viral uveitis 1/331 (0.3%) 1 0/326 (0%) 0
    Injury, poisoning and procedural complications
    Asbestosis 0/331 (0%) 0 1/326 (0.3%) 1
    Facial bones fracture 0/331 (0%) 0 1/326 (0.3%) 1
    Fall 2/331 (0.6%) 2 1/326 (0.3%) 1
    Hip fracture 2/331 (0.6%) 2 0/326 (0%) 0
    Injury 1/331 (0.3%) 1 0/326 (0%) 0
    Joint dislocation 0/331 (0%) 0 1/326 (0.3%) 1
    Lumbar vertebral fracture 0/331 (0%) 0 1/326 (0.3%) 1
    Rib fracture 0/331 (0%) 0 2/326 (0.6%) 2
    Upper limb fracture 1/331 (0.3%) 1 0/326 (0%) 0
    Investigations
    Intraocular pressure increased 1/331 (0.3%) 1 0/326 (0%) 0
    Weight decreased 1/331 (0.3%) 1 0/326 (0%) 0
    Metabolism and nutrition disorders
    Fluid overload 0/331 (0%) 0 1/326 (0.3%) 1
    Hyperkalaemia 0/331 (0%) 0 1/326 (0.3%) 1
    Hypokalaemia 0/331 (0%) 0 1/326 (0.3%) 1
    Vitamin B12 deficiency 0/331 (0%) 0 1/326 (0.3%) 1
    Musculoskeletal and connective tissue disorders
    Arthritis 1/331 (0.3%) 1 0/326 (0%) 0
    Back pain 1/331 (0.3%) 1 0/326 (0%) 0
    Fracture nonunion 1/331 (0.3%) 1 0/326 (0%) 0
    Lumbar spinal stenosis 1/331 (0.3%) 1 0/326 (0%) 0
    Muscular weakness 0/331 (0%) 0 1/326 (0.3%) 1
    Musculoskeletal stiffness 0/331 (0%) 0 1/326 (0.3%) 1
    Osteoarthritis 2/331 (0.6%) 2 1/326 (0.3%) 1
    Rhabdomyolysis 0/331 (0%) 0 1/326 (0.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma 1/331 (0.3%) 1 0/326 (0%) 0
    Bile duct cancer 0/331 (0%) 0 1/326 (0.3%) 1
    Bladder neoplasm 0/331 (0%) 0 1/326 (0.3%) 1
    Breast cancer stage IV 1/331 (0.3%) 1 0/326 (0%) 0
    Colon adenoma 0/331 (0%) 0 1/326 (0.3%) 1
    Extranodal marginal zone B-cell lymphoma (MALT type) 0/331 (0%) 0 1/326 (0.3%) 1
    Glioblastoma multiforme 0/331 (0%) 0 1/326 (0.3%) 1
    Lung cancer metastatic 0/331 (0%) 0 1/326 (0.3%) 1
    Lung neoplasm malignant 1/331 (0.3%) 1 0/326 (0%) 0
    Metastases to liver 0/331 (0%) 0 1/326 (0.3%) 1
    Ovarian cancer metastatic 1/331 (0.3%) 1 0/326 (0%) 0
    Pancreatic carcinoma 1/331 (0.3%) 1 1/326 (0.3%) 1
    Sarcomatoid carcinoma 0/331 (0%) 0 1/326 (0.3%) 1
    Sarcomatoid carcinoma of the lung 0/331 (0%) 0 1/326 (0.3%) 1
    Nervous system disorders
    Brain oedema 1/331 (0.3%) 1 0/326 (0%) 0
    Cerebral haemorrhage 0/331 (0%) 0 1/326 (0.3%) 1
    Cerebrovascular accident 1/331 (0.3%) 1 3/326 (0.9%) 6
    Ischaemic stroke 0/331 (0%) 0 2/326 (0.6%) 2
    Postictal paralysis 1/331 (0.3%) 1 0/326 (0%) 0
    Presyncope 1/331 (0.3%) 1 0/326 (0%) 0
    Seizure 0/331 (0%) 0 1/326 (0.3%) 1
    Subarachnoid haemorrhage 1/331 (0.3%) 1 0/326 (0%) 0
    Syncope 1/331 (0.3%) 1 2/326 (0.6%) 3
    Thrombotic cerebral infarction 1/331 (0.3%) 1 0/326 (0%) 0
    Transient ischaemic attack 1/331 (0.3%) 1 0/326 (0%) 0
    Product Issues
    Device malfunction 0/331 (0%) 0 1/326 (0.3%) 1
    Psychiatric disorders
    Mixed anxiety and depressive disorder 1/331 (0.3%) 1 0/326 (0%) 0
    Renal and urinary disorders
    Cystitis haemorrhagic 0/331 (0%) 0 1/326 (0.3%) 1
    Reproductive system and breast disorders
    Prostatomegaly 0/331 (0%) 0 1/326 (0.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/331 (0%) 0 1/326 (0.3%) 1
    Bronchiectasis 0/331 (0%) 0 1/326 (0.3%) 1
    Chronic obstructive pulmonary disease 1/331 (0.3%) 1 2/326 (0.6%) 2
    Dyspnoea 0/331 (0%) 0 2/326 (0.6%) 2
    Hypoxia 0/331 (0%) 0 1/326 (0.3%) 1
    Interstitial lung disease 0/331 (0%) 0 1/326 (0.3%) 1
    Lung perforation 0/331 (0%) 0 1/326 (0.3%) 1
    Pneumonitis 0/331 (0%) 0 1/326 (0.3%) 1
    Vascular disorders
    Hypertension 0/331 (0%) 0 1/326 (0.3%) 1
    Orthostatic hypotension 1/331 (0.3%) 1 1/326 (0.3%) 1
    Other (Not Including Serious) Adverse Events
    Arm A: Faricimab Arm B: Aflibercept
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 92/331 (27.8%) 79/326 (24.2%)
    Eye disorders
    Conjunctival haemorrhage 29/331 (8.8%) 38 32/326 (9.8%) 50
    Neovascular age-related macular degeneration 49/331 (14.8%) 54 39/326 (12%) 44
    Infections and infestations
    Nasopharyngitis 24/331 (7.3%) 25 16/326 (4.9%) 17

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

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

    Results Point of Contact

    Name/Title Medical Communications
    Organization Hoffmann-La Roche
    Phone 800-821-8590
    Email genentech@druginfo.com
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT03823300
    Other Study ID Numbers:
    • GR40844
    • 2018-004042-42
    First Posted:
    Jan 30, 2019
    Last Update Posted:
    Aug 1, 2022
    Last Verified:
    Jul 1, 2022