A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Neovascular Age-Related Macular Degeneration (TENAYA)
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 |
|---|---|---|
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Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Faricimab
|
Drug: Faricimab
Faricimab will be administered by intravitreal injection into the study eye at intervals as specified in the study protocol.
Other Names:
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 treatments arms at applicable visits to maintain masking.
|
| Active Comparator: 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:
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 treatments arms at applicable visits to maintain masking.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 [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.
- 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.
- Percentage of Participants in the Faricimab Arm on Once Every 8-Weeks, 12-Weeks, or 16-Weeks Treatment Intervals at Week 48 [Week 48]
- 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]
- Number of Study Drug Injections Received in the Study Eye Per Participant Through Week 48 [From Baseline through Week 48]
- Number of Study Drug Injections Received in the Study Eye Per Participant Through Weeks 60 and 112 [From Baseline through Weeks 60 and 112]
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Percentage of Participants With Absence of Intraretinal Cysts in the Study Eye Over Time [Up to 112 weeks]
- 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.
- 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.
- 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.
- 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.
- Percentage of Participants With Ocular Adverse Events During the Study [Up to 116 weeks]
- Percentage of Participants With Non-Ocular Adverse Events During the Study [Up to 116 weeks]
- Plasma Concentration of Faricimab Over Time [Pre-dose at Baseline, Weeks 4, 16, 20, 48, 76, and 112]
- 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
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 | Barnet Dulaney Perkins Eye Center | Mesa | Arizona | United States | 85206 |
| 2 | Retinal Research Institute, LLC | Phoenix | Arizona | United States | 85014 |
| 3 | Retina Associates Southwest PC | Tucson | Arizona | United States | 85704 |
| 4 | Retinal Diagnostic Center | Campbell | California | United States | 95008 |
| 5 | The Retina Partners | Encino | California | United States | 91436 |
| 6 | Jacobs Retina center at the Shiley eye Institute UCSD | La Jolla | California | United States | 92037 |
| 7 | South Coast Retina Center | Los Angeles | California | United States | 90033 |
| 8 | Southern CA Desert Retina Cons | Palm Desert | California | United States | 92211 |
| 9 | California Eye Specialists Medical group Inc. | Pasadena | California | United States | 91107 |
| 10 | Retina Consultants, San Diego | Poway | California | United States | 92064 |
| 11 | Retina Consultants of Southern California | Redlands | California | United States | 92373 |
| 12 | University of California, Davis, Eye Center | Sacramento | California | United States | 95817 |
| 13 | Retina Consultants of Southern | Colorado Springs | Colorado | United States | 80909 |
| 14 | Retina Group of New England | Waterford | Connecticut | United States | 06385 |
| 15 | Rand Eye | Deerfield Beach | Florida | United States | 33064 |
| 16 | Florida Eye Associates | Melbourne | Florida | United States | 32901 |
| 17 | Retina Specialty Institute | Pensacola | Florida | United States | 32503 |
| 18 | Fort Lauderdale Eye Institute | Plantation | Florida | United States | 33324 |
| 19 | Retina Vitreous Assoc of FL | Saint Petersburg | Florida | United States | 33711 |
| 20 | Northwestern Medical Group/Northwestern University | Chicago | Illinois | United States | 60611 |
| 21 | Retina Associates | Lenexa | Kansas | United States | 66215 |
| 22 | Johns Hopkins Med; Wilmer Eye Inst | Baltimore | Maryland | United States | 21287 |
| 23 | Retina Group of Washington | Chevy Chase | Maryland | United States | 20815 |
| 24 | Tufts Medical Center; Ophthalmology | Boston | Massachusetts | United States | 02111 |
| 25 | Associated Retinal Consultants | Grand Rapids | Michigan | United States | 49546 |
| 26 | Midwest Vision Research Foundation | Chesterfield | Missouri | United States | 63017 |
| 27 | Retina Associates of St. Louis | Florissant | Missouri | United States | 63031 |
| 28 | Sierra Eye Associates | Reno | Nevada | United States | 89502 |
| 29 | Mid Atlantic Retina - Wills Eye Hospital | Cherry Hill | New Jersey | United States | 08034 |
| 30 | NJ Retina | Edison | New Jersey | United States | 08820 |
| 31 | Retina Associates of NJ | Teaneck | New Jersey | United States | 07666 |
| 32 | Long Is. Vitreoretinal Consult | Great Neck | New York | United States | 11021 |
| 33 | Retina Vit Surgeons/Central NY | Liverpool | New York | United States | 13088 |
| 34 | Ophthalmic Cons of Long Island | Oceanside | New York | United States | 11572 |
| 35 | Retina Assoc of Western NY | Rochester | New York | United States | 14620 |
| 36 | The Retina Consultants | Slingerlands | New York | United States | 12159 |
| 37 | Western Carolina Retinal Associate PA | Asheville | North Carolina | United States | 28803 |
| 38 | Char Eye Ear &Throat Assoc | Charlotte | North Carolina | United States | 28210 |
| 39 | Graystone Eye | Hickory | North Carolina | United States | 28602 |
| 40 | Carolina Eye Associates | Southern Pines | North Carolina | United States | 28387 |
| 41 | Cincinnati Eye Institute | Cincinnati | Ohio | United States | 45242 |
| 42 | Retina Northwest | Portland | Oregon | United States | 97221 |
| 43 | Charleston Neuroscience Inst | Ladson | South Carolina | United States | 29456 |
| 44 | Black Hills Eye Institute | Rapid City | South Dakota | United States | 57701 |
| 45 | Charles Retina Institute | Memphis | Tennessee | United States | 38119 |
| 46 | Tennessee Retina PC. | Nashville | Tennessee | United States | 37203 |
| 47 | Retina Consultants of Texas | Bellaire | Texas | United States | 77401 |
| 48 | Texas Retina Associates | Dallas | Texas | United States | 75231 |
| 49 | Valley Retina Institute P.A. | Harlingen | Texas | United States | 78550 |
| 50 | Retina & Vitreous of Texas | Houston | Texas | United States | 77025 |
| 51 | Rocky Mountain Retina | Salt Lake City | Utah | United States | 84107 |
| 52 | Spokane Eye Clinical Research | Spokane | Washington | United States | 99204 |
| 53 | Calgary Retina Consultants | Calgary | Alberta | Canada | T2J 0C8 |
| 54 | University of British Columbia - Vancouver Coastal Health Authority | Vancouver | British Columbia | Canada | V5Z 1M9 |
| 55 | Ivey Eye Institute | London | Ontario | Canada | N6A 4V2 |
| 56 | University of Ottawa Eye Institute | Ottawa | Ontario | Canada | K1H 8L6 |
| 57 | The Retina Centre of Ottawa | Ottawa | Ontario | Canada | K2B 7E9 |
| 58 | Toronto Retina Institute | Toronto | Ontario | Canada | M3C 0G9 |
| 59 | Unity Health Toronto | Toronto | Ontario | Canada | M5B IW8 |
| 60 | Institut De L'Oeil Des Laurentides | Boisbriand | Quebec | Canada | J7H 0E8 |
| 61 | Michel Giunta Clinique Medical | Sherbrooke | Quebec | Canada | J1G 2V4 |
| 62 | Universitätsklinikum Freiburg, Klinik für Augenheilkunde | Freiburg | Germany | 79106 | |
| 63 | Universitätsklinik Heidelberg; Augenklinik | Heidelberg | Germany | 69120 | |
| 64 | Universitätsklinikum Tübingen | Tübingen | Germany | 72076 | |
| 65 | Budapest Retina Associates Kft. | Budapest | Hungary | 1133 | |
| 66 | Debreceni Egyetem Klinikai Kozpont; Szemeszeti Klinika | Debrecen | Hungary | 4032 | |
| 67 | Ganglion Medial Center | Pécs | Hungary | 7621 | |
| 68 | Zala Megyei Kórház; SZEMESZET | Zalaegerszeg | Hungary | 8900 | |
| 69 | Rambam Medical Center; Opthalmology | Haifa | Israel | 3109601 | |
| 70 | Hadassah MC; Ophtalmology | Jerusalem | Israel | 9112001 | |
| 71 | Rabin MC; Ophtalmology | Petach Tikva | Israel | 4941492 | |
| 72 | Kaplan Medical Center; Ophtalmology | Rehovot | Israel | 7660101 | |
| 73 | Tel Aviv Sourasky MC; Ophtalmology | Tel Aviv | Israel | 6423906 | |
| 74 | Fondazione G.B. Bietti Per Lo Studio E La Ricerca in Oftalmologia-Presidio Ospedaliero Britannico | Roma | Lazio | Italy | 00198 |
| 75 | Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico-Clinica Regina Elena;U.O.C Oculistica | Milano | Lombardia | Italy | 20100 |
| 76 | Azienda Ospedaliera di Perugia Ospedale S. Maria Della Misericordia; Clinica Oculistica | Perugia | Umbria | Italy | 06129 |
| 77 | Chukyo Hospital | Aichi | Japan | 457-8510 | |
| 78 | Nagoya University Hospital | Aichi | Japan | 466-8560 | |
| 79 | Nagoya City University Hospital | Aichi | Japan | 467-8602 | |
| 80 | Aichi Medical University Hospital | Aichi | Japan | 480-1195 | |
| 81 | Daiyukai Daiichi Hospital | Aichi | Japan | 491-8551 | |
| 82 | Chiba University Hospital | Chiba | Japan | 260-8677 | |
| 83 | Toho University Sakura Medical Center | Chiba | Japan | 285-8741 | |
| 84 | Hayashi Eye Hospital | Fukuoka | Japan | 812-0011 | |
| 85 | Kurume University Hospital | Fukuoka | Japan | 830-0011 | |
| 86 | Fukushima Medical University Hospital | Fukushima | Japan | 960-1295 | |
| 87 | Southern TOHOKU Eye Clinic | Fukushima | Japan | 963-8052 | |
| 88 | Sapporo City General Hospital | Hokkaido | Japan | 060-8604 | |
| 89 | Hokkaido University Hospital | Hokkaido | Japan | 060-8648 | |
| 90 | Asahikawa Medical University Hospital | Hokkaido | Japan | 078-8510 | |
| 91 | Hyogo Prefectural Amagasaki General Medical Center (Hyogo AGMC) | Hyogo | Japan | 660-8550 | |
| 92 | Hyogo College of Medicine Hospital | Hyogo | Japan | 663-8501 | |
| 93 | Kozawa eye hospital and diabetes center | Ibaraki | Japan | 310-0845 | |
| 94 | Kagawa University Hospital | Kagawa | Japan | 761-0793 | |
| 95 | Kagoshima University Hospital | Kagoshima | Japan | 890-8520 | |
| 96 | Ideta Eye Hospital | Kumamoto | Japan | 860-0027 | |
| 97 | Kyoto University Hospital | Kyoto | Japan | 606-8507 | |
| 98 | Mie University Hospital | Mie | Japan | 514-8507 | |
| 99 | University of Miyazaki Hospital | Miyazaki | Japan | 889-1692 | |
| 100 | Shinshu University Hospital | Nagano | Japan | 390-8621 | |
| 101 | Iida Municipal Hospital | Nagano | Japan | 395-8502 | |
| 102 | Japanese Red Cross Nagasaki Genbaku Hospital | Nagasaki | Japan | 852-8511 | |
| 103 | Nara Medical University Hospital | Nara | Japan | 634-8522 | |
| 104 | University of the Ryukyus Hospital | Okinawa | Japan | 903-0125 | |
| 105 | Kitano Hospital | Osaka | Japan | 530-8480 | |
| 106 | Osaka City University Hospital | Osaka | Japan | 545-8586 | |
| 107 | Kansai Medical University Medical Center | Osaka | Japan | 570-8507 | |
| 108 | Kansai Medical University Hospital | Osaka | Japan | 573-1191 | |
| 109 | National Defense Medical College Hospital | Saitama | Japan | 359-8513 | |
| 110 | Shiga University Of Medical Science Hospital | Shiga | Japan | 520-2192 | |
| 111 | Tokushima University Hospital | Tokushima | Japan | 770-8503 | |
| 112 | Nihon University Hospital | Tokyo | Japan | 101-8309 | |
| 113 | Takeuchi eye clinic | Tokyo | Japan | 111-0051 | |
| 114 | Tokyo Women's Medical University Hospital | Tokyo | Japan | 162-8666 | |
| 115 | Kyorin University Hospital | Tokyo | Japan | 181-8611 | |
| 116 | Tokyo Medical University Hachioji Medical Center | Tokyo | Japan | 193-0998 | |
| 117 | Yamaguchi University Hospital | Yamaguchi | Japan | 755-8505 | |
| 118 | Centro Oftalmológico Mira, S.C | Del. Cuauhtemoc | Mexico CITY (federal District) | Mexico | 06760 |
| 119 | Macula Retina Consultores | Mexico, D.F. | Mexico | 01120 | |
| 120 | Montemayor & Asociados (Oftalmologos) | Monterrey Nuevo LEON | Mexico | 64060 | |
| 121 | Het Oogziekenhuis Rotterdam | Rotterdam | Netherlands | 3011 BH | |
| 122 | ETZ Elisabeth | Tilburg | Netherlands | 5022 GC | |
| 123 | Szpital sw. Lukasza | Bielsko-Biala | Poland | 43-309 | |
| 124 | Specjalistyczny Ośrodek Okulistyczny Oculomedica | Bydgoszcz | Poland | 85-870 | |
| 125 | Szpital Specjalistyczny nr 1; Oddzial Okulistyki | Bytom | Poland | 41-902 | |
| 126 | Dobry Wzrok Sp Z O O | Gdańsk | Poland | 80-402 | |
| 127 | Gabinet Okulistyczny Prof Edward Wylegala | Katowice | Poland | 40-594 | |
| 128 | Centrum Medyczne Dietla 19 Sp. Z O.O. | Kraków | Poland | 31-070 | |
| 129 | SPEKTRUM Osrodek Okulistyki Klinicznej | Wroclaw | Poland | 53-334 | |
| 130 | Clinics of Eye Diseases, LLC | Kazan | Tatarstan | Russian Federation | 420066 |
| 131 | FSBI "Scientific Research Institute of Eye Diseases" of Russian Academy of medical Sciences | Moscow | Russian Federation | 119435 | |
| 132 | Medical Military Academy n.a S.M.Kirov | St.Petersburg | Russian Federation | 194044 | |
| 133 | Hospital General de Catalunya | San Cugat Del Valles | Barcelona | Spain | 08195 |
| 134 | Instituto Oftalmologico Gomez Ulla; Servicio de Oftalmologia | Santiago de Compostela | LA Coruña | Spain | 15706 |
| 135 | Hospital Universitario Puerta de Hierro | Majadahonda | Madrid | Spain | 28222 |
| 136 | Clinica Universitaria de Navarra; Servicio de Oftalmologia | Pamplona | Navarra | Spain | 31008 |
| 137 | Oftalvist Valencia | Burjassot | Valencia | Spain | 46100 |
| 138 | Hospital dos de maig; servicio de oftalmologia | Barcelona | Spain | 08025 | |
| 139 | Clinica Universitaria de Navarra; Servicio de Oftalmologia | Madrid | Spain | 28027 | |
| 140 | Clinica Baviera; Servicio Oftalmologia | Madrid | Spain | 28046 | |
| 141 | Vista Klinik Ophthalmologische Klinik | Binningen | Switzerland | 4102 | |
| 142 | Stadtspital Triemli Ophthalmologische Klinik | Zürich | Switzerland | 8063 | |
| 143 | Ankara Baskent University Medical Faculty; Department of Ophthalmology | Ankara | Turkey | 06490 | |
| 144 | Kocaeli Üniversitesi Tıp Fakültesi; Department of Ophthalmology | Kocaeli | Turkey | 41380 | |
| 145 | Selcuk University Faculty of Medicine; Department Of Ophthalmology | Konya | Turkey | 42130 | |
| 146 | Bradford Royal Infirmary | Bradford | United Kingdom | BD9 6RJ | |
| 147 | Bristol Eye Hospital | Bristol | United Kingdom | BS1 2LX | |
| 148 | University Hospital of Wales | Cardiff | United Kingdom | CF14 4XW | |
| 149 | Frimley Park Hospital | Frimley | United Kingdom | GU16 7UJ | |
| 150 | Gloucestershire Royal Hospital | Gloucester | United Kingdom | GL1 3NN | |
| 151 | Hull Royal Infirmary | Hull | United Kingdom | HU3 2JZ | |
| 152 | St James University Hospital | Leeds | United Kingdom | LS9 7TF | |
| 153 | Royal Liverpool University Hospital; St Paul's Clinical Eye Research Centre | Liverpool | United Kingdom | L7 8XP | |
| 154 | Moorfields Eye Hospital NHS Foundation Trust | London | United Kingdom | EC1V 2PD | |
| 155 | Royal Free Hospital | London | United Kingdom | NW3 2QS | |
| 156 | Manchester Royal Infirmary | Manchester | United Kingdom | M13 9WL | |
| 157 | Royal Victoria Infirmary | Newcastle upon Tyne | United Kingdom | NE1 4LP | |
| 158 | Southampton General Hospital | Southampton | United Kingdom | SO16 6YD | |
| 159 | New Cross Hospital | Wolverhampton | United Kingdom | WV10 0QP | |
| 160 | The York Hospital | York | United Kingdom | YO31 8HE |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
More Information
Publications
None provided.- GR40306
- 2018-002152-32
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 | 334 | 337 |
| Received at Least One Dose of Study Drug | 333 | 336 |
| Completed up to Week 48 | 319 | 323 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 334 | 337 |
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 | 334 | 337 | 671 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
75.9
(8.6)
|
76.7
(8.8)
|
76.3
(8.7)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
191
57.2%
|
211
62.6%
|
402
59.9%
|
| Male |
143
42.8%
|
126
37.4%
|
269
40.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
26
7.8%
|
26
7.7%
|
52
7.7%
|
| Not Hispanic or Latino |
303
90.7%
|
308
91.4%
|
611
91.1%
|
| Unknown or Not Reported |
5
1.5%
|
3
0.9%
|
8
1.2%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| White |
303
90.7%
|
302
89.6%
|
605
90.2%
|
| Asian |
26
7.8%
|
28
8.3%
|
54
8%
|
| Black or African American |
0
0%
|
3
0.9%
|
3
0.4%
|
| American Indian or Alaska Native |
1
0.3%
|
2
0.6%
|
3
0.4%
|
| Multiple |
1
0.3%
|
0
0%
|
1
0.1%
|
| Unknown |
3
0.9%
|
2
0.6%
|
5
0.7%
|
| Region of Enrollment (Count of Participants) | |||
| United States and Canada |
182
54.5%
|
184
54.6%
|
366
54.5%
|
| Asia |
26
7.8%
|
26
7.7%
|
52
7.7%
|
| Rest of the World |
126
37.7%
|
127
37.7%
|
253
37.7%
|
| Number of Participants by the Eye (Right or Left) Chosen as the Study Eye (Count of Participants) | |||
| Right Eye |
166
49.7%
|
178
52.8%
|
344
51.3%
|
| Left Eye |
168
50.3%
|
159
47.2%
|
327
48.7%
|
| Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye (ETDRS Letters) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [ETDRS Letters] |
61.3
(12.5)
|
61.5
(12.9)
|
61.4
(12.7)
|
| Number of Participants by the BCVA Letter Score Categories in the Study Eye (Count of Participants) | |||
| ≥74 Letters |
47
14.1%
|
52
15.4%
|
99
14.8%
|
| 73 to 55 Letters |
200
59.9%
|
201
59.6%
|
401
59.8%
|
| ≤54 Letters |
87
26%
|
84
24.9%
|
171
25.5%
|
| Number of Participants by the Low Luminance Deficit (LLD) Letter Score Categories in the Study Eye (Count of Participants) | |||
| <33 Letters |
236
70.7%
|
235
69.7%
|
471
70.2%
|
| ≥33 Letters |
95
28.4%
|
98
29.1%
|
193
28.8%
|
| Missing/Invalid |
3
0.9%
|
4
1.2%
|
7
1%
|
| Choroidal Neovascularization (CNV) Lesion Type in the Study Eye by Fundus Fluorescein Angiography (Count of Participants) | |||
| Occult |
177
53%
|
174
51.6%
|
351
52.3%
|
| Classic |
84
25.1%
|
73
21.7%
|
157
23.4%
|
| Minimally Classic |
32
9.6%
|
30
8.9%
|
62
9.2%
|
| Retinal Angiomatous Proliferation (RAP) |
14
4.2%
|
27
8%
|
41
6.1%
|
| Predominantly Classic |
17
5.1%
|
19
5.6%
|
36
5.4%
|
| Polypoidal Choroidal Vasculopathy (PCV) |
6
1.8%
|
6
1.8%
|
12
1.8%
|
| Missing |
4
1.2%
|
8
2.4%
|
12
1.8%
|
Outcome Measures
| 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 | 334 | 337 |
| Mean (95% Confidence Interval) [ETDRS Letters] |
5.8
|
5.1
|
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 | 0.7 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 2.5 |
|
| 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. | |
| 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 | 334 | 337 |
| Mean (95% Confidence Interval) [ETDRS Letters] |
5.4
|
4.6
|
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 | 0.7 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to 2.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.99 |
|
| Estimation Comments | The adjusted mean difference was calculated as Arm A: Faricimab minus Arm B: Aflibercept. | |
| 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 |
| 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 | 292 | 300 |
| Gaining ≥15 Letters |
20.0
6%
|
15.7
4.7%
|
| Gaining ≥10 Letters |
37.1
11.1%
|
31.7
9.4%
|
| Gaining ≥5 Letters |
59.2
17.7%
|
58.0
17.2%
|
| Gaining ≥0 Letters |
75.6
22.6%
|
76.8
22.8%
|
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 | 4.3 | |
| Confidence Interval |
(2-Sided) 95% -1.6 to 10.1 |
|
| 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 | 5.4 | |
| Confidence Interval |
(2-Sided) 95% -2.0 to 12.7 |
|
| 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 | 1.2 | |
| Confidence Interval |
(2-Sided) 95% -6.6 to 8.9 |
|
| 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 | -1.2 | |
| Confidence Interval |
(2-Sided) 95% -7.9 to 5.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| 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 | 277 | 283 |
| Number (95% Confidence Interval) [Percentage of participants] |
19.2
5.7%
|
16.6
4.9%
|
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 | 2.7 | |
| Confidence Interval |
(2-Sided) 95% -3.2 to 8.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The difference in CMH weighted percentage of participants was calculated as Arm A: Faricimab minus Arm B: Aflibercept. | |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 | 292 | 300 |
| Avoiding a Loss of ≥15 Letters |
95.4
28.6%
|
94.1
27.9%
|
| Avoiding a Loss of ≥10 Letters |
91.6
27.4%
|
92.0
27.3%
|
| Avoiding a Loss of ≥5 Letters |
88.0
26.3%
|
86.8
25.8%
|
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 | 1.3 | |
| Confidence Interval |
(2-Sided) 95% -2.2 to 4.8 |
|
| 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 | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -4.6 to 3.9 |
|
| 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 | 1.2 | |
| Confidence Interval |
(2-Sided) 95% -4.0 to 6.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| 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 | 277 | 283 |
| Number (95% Confidence Interval) [Percentage of participants] |
93.9
28.1%
|
94.1
27.9%
|
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 | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -3.9 to 3.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The difference in CMH weighted percentage of participants was calculated as Arm A: Faricimab minus Arm B: Aflibercept. | |
| 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 |
| 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 |
| 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 |
| 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 | 292 | 300 |
| Number (95% Confidence Interval) [Percentage of participants] |
24.3
7.3%
|
21.3
6.3%
|
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 | 3.0 | |
| Confidence Interval |
(2-Sided) 95% -3.6 to 9.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The difference in CMH weighted percentage of participants was calculated as Arm A: Faricimab minus Arm B: Aflibercept. | |
| 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 |
| 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 | 292 | 300 |
| Number (95% Confidence Interval) [Percentage of participants] |
56.4
16.9%
|
57.0
16.9%
|
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 | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -7.7 to 6.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The difference in CMH weighted percentage of participants was calculated as Arm A: Faricimab minus Arm B: Aflibercept. | |
| 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 |
| 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 | 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 | 292 | 300 |
| Number (95% Confidence Interval) [Percentage of participants] |
6.4
1.9%
|
6.9
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 | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -4.2 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. | |
| 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 |
| 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 | 315 |
| Once Every 8 Weeks |
20.3
6.1%
|
| Once Every 12 Weeks |
34.0
10.2%
|
| Once Every 16 Weeks |
45.7
13.7%
|
| 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 |
| 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 | 334 | 337 |
| Median (Inter-Quartile Range) [Injections per participant] |
7.0
|
8.0
|
| 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 |
| 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 | 334 | 337 |
| Mean (95% Confidence Interval) [microns] |
-136.8
|
-129.4
|
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 | Adjusted mean difference |
| Estimated Value | -7.4 | |
| Confidence Interval |
(2-Sided) 95% -15.7 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.19 |
|
| Estimation Comments | The adjusted mean difference was calculated as Arm A: Faricimab minus Arm B: Aflibercept. | |
| 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 | 334 | 337 |
| Mean (95% Confidence Interval) [microns] |
-134.5
|
-135.5
|
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 | 1.0 | |
| Confidence Interval |
(2-Sided) 95% -7.4 to 9.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.26 |
|
| Estimation Comments | The adjusted mean difference was calculated as Arm A: Faricimab minus Arm B: Aflibercept. | |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 | 237 | 248 |
| Mean (Standard Deviation) [millimetres squared (mm^2)] |
0.0
(4.5)
|
0.4
(4.8)
|
| 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 |
| 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 | 243 | 246 |
| Mean (Standard Deviation) [millimetres squared (mm^2)] |
-3.8
(6.9)
|
-3.0
(6.9)
|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 | 5/333 (1.5%) | 1/336 (0.3%) | ||
Serious Adverse Events |
||||
| Arm A: Faricimab | Arm B: Aflibercept | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 34/333 (10.2%) | 44/336 (13.1%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Cardiac disorders | ||||
| Acute left ventricular failure | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Acute myocardial infarction | 1/333 (0.3%) | 1 | 1/336 (0.3%) | 1 |
| Angina pectoris | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Atrial fibrillation | 3/333 (0.9%) | 3 | 3/336 (0.9%) | 3 |
| Cardiac failure | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Cardiac failure congestive | 1/333 (0.3%) | 1 | 1/336 (0.3%) | 1 |
| Mitral valve prolapse | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Pericarditis constrictive | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Eye disorders | ||||
| Age-related macular degeneration | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Cataract | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Neovascular age-related macular degeneration | 1/333 (0.3%) | 1 | 5/336 (1.5%) | 5 |
| Retinal pigment epithelial tear | 2/333 (0.6%) | 2 | 0/336 (0%) | 0 |
| Rhegmatogenous retinal detachment | 0/333 (0%) | 0 | 2/336 (0.6%) | 2 |
| Subretinal fibrosis | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Uveitis | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Abdominal pain | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Constipation | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Diarrhoea | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Gastrointestinal haemorrhage | 0/333 (0%) | 0 | 2/336 (0.6%) | 2 |
| Hiatus hernia | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Ileus | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Incarcerated inguinal hernia | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Intestinal obstruction | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Upper gastrointestinal haemorrhage | 1/333 (0.3%) | 1 | 1/336 (0.3%) | 1 |
| General disorders | ||||
| Asthenia | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Gait disturbance | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Multiple organ dysfunction syndrome | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Cholecystitis | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Cholelithiasis | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Infections and infestations | ||||
| Arthritis bacterial | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Biliary sepsis | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Bronchitis | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| COVID-19 | 1/333 (0.3%) | 1 | 1/336 (0.3%) | 1 |
| Lung abscess | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Pneumonia | 1/333 (0.3%) | 1 | 3/336 (0.9%) | 3 |
| Pneumonia bacterial | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Post procedural infection | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Sepsis | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Septic shock | 2/333 (0.6%) | 2 | 0/336 (0%) | 0 |
| Sinusitis | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Systemic bacterial infection | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Urinary tract infection | 1/333 (0.3%) | 1 | 1/336 (0.3%) | 1 |
| Viral uveitis | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Anaemia postoperative | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Arthropod bite | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Corneal abrasion | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Fall | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Femur fracture | 0/333 (0%) | 0 | 2/336 (0.6%) | 2 |
| Ligament sprain | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Spinal compression fracture | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Toxicity to various agents | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Hypokalaemia | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Osteoarthritis | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Biliary neoplasm | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Gastric cancer | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Hair follicle tumour benign | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Lung neoplasm malignant | 1/333 (0.3%) | 1 | 1/336 (0.3%) | 1 |
| Meningioma | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Neuroendocrine carcinoma metastatic | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Rectal cancer | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Tongue neoplasm malignant stage unspecified | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Nervous system disorders | ||||
| Cerebrovascular accident | 2/333 (0.6%) | 2 | 1/336 (0.3%) | 1 |
| Dizziness | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Encephalopathy | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Somnolence | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Syncope | 1/333 (0.3%) | 1 | 1/336 (0.3%) | 1 |
| Transient ischaemic attack | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Psychiatric disorders | ||||
| Major depression | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 0/333 (0%) | 0 | 2/336 (0.6%) | 2 |
| Chronic kidney disease | 2/333 (0.6%) | 2 | 0/336 (0%) | 0 |
| Haematuria | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Urinary retention | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Pleural effusion | 1/333 (0.3%) | 1 | 0/336 (0%) | 0 |
| Pneumonia aspiration | 1/333 (0.3%) | 1 | 1/336 (0.3%) | 1 |
| Pulmonary embolism | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Rash | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Vascular disorders | ||||
| Deep vein thrombosis | 0/333 (0%) | 0 | 1/336 (0.3%) | 1 |
| Hypertension | 1/333 (0.3%) | 1 | 1/336 (0.3%) | 2 |
Other (Not Including Serious) Adverse Events |
||||
| Arm A: Faricimab | Arm B: Aflibercept | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 68/333 (20.4%) | 87/336 (25.9%) | ||
| Eye disorders | ||||
| Conjunctival haemorrhage | 23/333 (6.9%) | 25 | 26/336 (7.7%) | 30 |
| Neovascular age-related macular degeneration | 36/333 (10.8%) | 44 | 41/336 (12.2%) | 47 |
| Infections and infestations | ||||
| Nasopharyngitis | 18/333 (5.4%) | 20 | 28/336 (8.3%) | 31 |
Limitations/Caveats
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 |
| genentech@druginfo.com |
- GR40306
- 2018-002152-32