A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Macular Edema Secondary to Central Retinal or Hemiretinal Vein Occlusion
- Conditions
- Central Retinal Vein OcclusionHemiretinal Vein OcclusionMacular Edema
- Interventions
- Registration Number
- NCT04740931
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is a Phase III, multicenter, randomized, double-masked, active comparator-controlled, parallel-group study evaluating the efficacy, safety, and pharmacokinetics of faricimab administered by intravitreal (IVT) injection at 4-week intervals until Week 24, followed by a double-masked period of study without active control to evaluate faricimab administered according to a personalized treatment interval (PTI) dosing regimen in patients with macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 729
- Foveal center-involved macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO), diagnosed no longer than 4 months prior to the screening visit
- Best-corrected visual acuity (BCVA) of 73 to 19 letters, inclusive (20/40 to 20/400 approximate Snellen equivalent)
- Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition of good quality retinal images to confirm diagnosis
- For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs during the treatment period and for 3 months after the final dose of study treatment
- Any major illness or major surgical procedure within 1 month before screening
- Uncontrolled blood pressure
- Stroke (cerebral vascular accident) or myocardial infarction within 6 months prior to Day 1
- Pregnant or breastfeeding, or intending to become pregnant during the study
Ocular Exclusion Criteria for Study Eye:
- History of previous episodes of macular edema due to RVO or persistent macular edema due to RVO diagnosed more than 4 months before screening
- Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than macular edema due to RVO in the study eye (e.g., ischemic maculopathy, Irvine-Gass syndrome, foveal atrophy, foveal fibrosis, pigment abnormalities, dense subfoveal hard exudates, or other non-retinal conditions)
- Macular laser (focal/grid) in the study eye at any time prior to Day 1
- Panretinal photocoagulation in the study eye within 3 months prior to Day 1 or anticipated within 3 months of study start on Day 1
- Any prior or current treatment for macular edema; macular neovascularization, including diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD); and vitreomacular-interface abnormalities, including, but not restricted to, IVT treatment with anti-VEGF, steroids, tissue plasminogen activator, ocriplasmin, C3F8, air or periocular injection
- Any prior intervention with verteporfin photodynamic therapy, diode laser, transpupillary thermotherapy, or vitreo-retinal surgery including sheathotomy
- Any prior steroid implant use including dexamethasone intravitreal implant (Ozurdex) and fluocinolone acetonide intravitreal implant (Iluvien)
Ocular Exclusion Criteria for Both Eyes:
- Prior IVT administration of faricimab in either eye
- History of idiopathic or autoimmune-associated uveitis in either eye
- Active periocular, ocular or intraocular inflammation or infection (including suspected) in either eye on Day 1
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) Sham Procedure In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm B will receive aflibercept 2 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants will receive faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure will be administered during study visits at which no faricimab treatment is administered (according to the PTI dosing regimen). Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) Sham Procedure In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm A will receive faricimab 6 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants will receive faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure will be administered during study visits at which no faricimab treatment is administered (according to the PTI dosing regimen). Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) Faricimab In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm A will receive faricimab 6 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants will receive faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure will be administered during study visits at which no faricimab treatment is administered (according to the PTI dosing regimen). Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) Faricimab In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm B will receive aflibercept 2 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants will receive faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure will be administered during study visits at which no faricimab treatment is administered (according to the PTI dosing regimen). Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) Aflibercept In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm B will receive aflibercept 2 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants will receive faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure will be administered during study visits at which no faricimab treatment is administered (according to the PTI dosing regimen).
- Primary Outcome Measures
Name Time Method Part 1: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye at Week 24 From Baseline through Week 24 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), and randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
- Secondary Outcome Measures
Name Time Method Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Change From Baseline in BCVA in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), and randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye at Week 24 From Baseline through Week 24 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Percentage of Participants With Absence of Macular Edema in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Absence of diabetic macular edema was defined as achieving a central subfield thickness of \<325 microns in the study eye. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Intraretinal fluid and subretinal fluid were measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Percentage of Participants Achieving ≥84 Letters in BCVA (20/20 Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Percentage of Participants With Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Subretinal fluid was measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Change From Baseline in National Eye Institute 25-Item Visual Functioning Questionnaire (NEI VFQ-25) Composite Score at Week 24 Baseline and Week 24 The NEI VFQ-25 captures a patient's perception of vision-related functioning and vision-related quality of life. The core measure includes 25 items that comprise 11 vision-related subscales and 1 item on general health. The composite score ranges from 0 to 100, with higher scores indicating better vision-related functioning. For the ANCOVA analysis, the model uses the non-missing change from baseline in BCVA at Weeks 24 as the response variables adjusted for the treatment group, baseline NEI VFQ-25 Composite Score (continuous), baseline BCVA score (≥55 and ≤54 letters) and region (U.S. and Canada, Asia, and the rest of the world). Observed NEI VFQ-25 assessments were used regardless of the occurrence of intercurrent events. Missing data were not imputed. 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Percentage of Participants Achieving ≥69 Letters in BCVA (20/40 or Better Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Percentage of Participants Achieving ≥84 Letters in BCVA (20/20 Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Percentage of Participants Achieving ≥69 Letters in BCVA (20/40 or Better Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Percentage of Participants With ≤38 Letters in BCVA (20/200 or Worse Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (\>38 and ≤38 letters) and region (U.S. and Canada, Asia, and rest of the world). All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Intraretinal fluid was measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Change From Baseline in BCVA in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), and randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
Part 1: Percentage of Participants Gaining >0 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Percentage of Participants Gaining >0 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Percentage of Participants With ≤38 Letters in BCVA (20/200 or Worse Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (\>38 and ≤38 letters) and region (U.S. and Canada, Asia, and rest of the world). All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 1: Change From Baseline in Central Subfield Thickness in the Study Eye at Specified Timepoints Through Week 24 Baseline, Weeks 4, 8, 12, 16, 20, and 24 Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the Bruch's membrane (BM) using optical coherence tomography (OCT), as assessed by the central reading center. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline CST (continuous), and randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Change From Baseline in Central Subfield Thickness in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline CST (continuous), and randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Change From Baseline in NEI VFQ-25 Questionnaire Composite Score at Specified Timepoints Through Week 72 Baseline, Weeks 24, 48, and 72 The NEI VFQ-25 captures a patient's perception of vision-related functioning and vision-related quality of life. The core measure includes 25 items that comprise 11 vision-related subscales and 1 item on general health. The composite score ranges from 0 to 100, with higher scores indicating better vision-related functioning. For the MMRM analysis, the model adjusted for the treatment group, visit, visit-by-treatment group interaction, baseline NEI VFQ-25 Composite Score continuous), baseline BCVA score (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and the rest of the world). Observed NEI VFQ-25 assessments were used regardless of the occurrence of intercurrent events. Missing data were implicitly imputed. Invalid BCVA values were excluded. 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Percentage of Participants With Absence of Macular Edema in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Absence of diabetic macular edema was defined as achieving a central subfield thickness of \<325 microns in the study eye. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Intraretinal fluid was measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Parts 1 and 2: Percentage of Participants With Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Subretinal fluid was measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 2: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Week 24 in the Study Eye at Specified Timepoints Through Week 72 Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale Part 1: From first dose up to Week 24; Part 2: from Week 24 through Week 72 This analysis of adverse events (AEs) only includes ocular AEs that occurred in the study eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. Ocular AEs of special interest included the following: Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation (IOI).
Number of Participants With Anti-Drug Antibodies (ADAs) to Faricimab at Baseline and Post-Baseline During the Study Predose at Day 1 (Baseline), Weeks 4, 24, 28, 52, and 72 Anti-drug antibodies (ADAs) against fariciamb were detected in plasma using a validated bridging enzyme-linked immunosorbent assay (ELISA). The number of participants with treatment-emergent ADA-positive samples includes post-baseline evaluable participants with at least one treatment-induced (defined as having an ADA-negative sample or missing sample at baseline and any positive post-baseline sample) or treatment-boosted (defined as having an ADA-positive sample at baseline and any positive post-baseline sample with a titer that is equal to or greater than 4-fold baseline titer) ADA-positive sample during the study treatment period. Treatment-unaffected ADA-positive is a post-baseline sample with a titer that is lower than 4-fold the ADA-positive baseline titer (faricimab arm) or the ADA-positive titer prior to first faricimab injection (aflibercept arm).
Parts 1 and 2: Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 72 Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Intraretinal fluid and subretinal fluid were measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 2: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Week 24 in the Study Eye at Specified Timepoints Through Week 72 Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 2: Number of Study Drug Injections Received in the Study Eye From Week 24 Through Week 72 From Week 24 to Week 72 Part 2: Change From Week 24 in BCVA in the Study Eye at Specified Timepoints Through Week 72 Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), and randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
Part 2: Percentage of Participants Avoiding a Loss of >0 Letters in BCVA From Week 24 in the Study Eye at Specified Timepoints Through Week 72 Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Incidence of Ocular Adverse Events in the Fellow Eye Part 1: From first dose up to Week 24; Part 2: from Week 24 through Week 72 This analysis of adverse events (AEs) only includes ocular AEs that occurred in the fellow eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. Ocular AEs of special interest included the following: Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation (IOI).
Incidence of Non-Ocular Adverse Events Part 1: From first dose up to Week 24; Part 2: from Week 24 through Week 72 This analysis of adverse events (AEs) only includes non-ocular (systemic) AEs. Investigators sought information on adverse events (AEs) at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. The non-ocular AE of special interest was: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.
Plasma Concentration of Faricimab Over Time Predose at Day 1 (Baseline), Weeks 4, 24, 28, 52, and 72 Part 2: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Week 24 in the Study Eye at Specified Timepoints Through Week 72 Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≤34, 35-54, and ≥55 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Part 2: Percentage of Participants on Different Treatment Intervals at Week 68 Week 68 In Part 2 of the study, participants in both the faricimab Q4W and aflibercept Q4W arms in Part 1 received 6 mg faricimab intravitreal injections administered according to a personalized treatment interval (PTI) dosing regimen in intervals between Q4W and Q16W. At faricimab dosing visits, treatment intervals were maintained or adjusted (i.e., increased by 4 weeks or decreased by 4, 8, or 12 weeks), based on central subfield thickness (CST) and BCVA values.
Trial Locations
- Locations (194)
Fort Lauderdale Eye Institute
🇺🇸Plantation, Florida, United States
Assoc Retinal Consultants PC
🇺🇸Royal Oak, Michigan, United States
Midwest Vision Research Foundation
🇺🇸Chesterfield, Missouri, United States
Texas Retina Associates
🇺🇸Dallas, Texas, United States
West Virginia University Eye Institute
🇺🇸Morgantown, West Virginia, United States
Sydney Retina Clinic and Day Surgery
🇦🇺Sydney, New South Wales, Australia
Hadassah MC; Ophtalmology
🇮🇱Jerusalem, Israel
Barnet Dulaney Perkins Eye Center
🇺🇸Mesa, Arizona, United States
Buenos Aires Mácula
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Sierra Eye Associates
🇺🇸Reno, Nevada, United States
Kurume University Hospital
🇯🇵Fukuoka, Japan
Kansai Medical University Medical Center
🇯🇵Osaka, Japan
Dobry Wzrok Sp Z O O
🇵🇱Gda?sk, Poland
Retina Associates Southwest PC
🇺🇸Tucson, Arizona, United States
Oftar
🇦🇷Mendoza, Argentina
Budapest Retina Associates Kft.
🇭🇺Budapest, Hungary
Tel Aviv Sourasky MC; Ophtalmology
🇮🇱Tel Aviv, Israel
Bajcsy-Zsilinszky Hospital
🇭🇺Budapest, Hungary
Szegedi Tudományegyetem ÁOK; Department of Ophtalmology
🇭🇺Szeged, Hungary
Retina Group of New England
🇺🇸Waterford, Connecticut, United States
Rambam Medical Center; Opthalmology
🇮🇱Haifa, Israel
Kaplan Medical Center; Ophtalmology
🇮🇱Rehovot, Israel
Sugita Eye Hospital
🇯🇵Aichi, Japan
Nagoya University Hospital
🇯🇵Aichi, Japan
Toho University Sakura Medical Center
🇯🇵Chiba, Japan
MT Medic Krosno
🇵🇱Krosno, Poland
Intersec Research and Technology Complex ?Eye Microsurgery? n.a. S.N. Fyodorov; Cheboksary Branch
🇷🇺Cheboksary, Marij EL, Russian Federation
Hospital General de Catalunya
🇪🇸San Cugat Del Valles, Barcelona, Spain
1 Saint-Petersburg St. Med. University named after academician I.P.Pavlov; Chair of ophathalmology
🇷🇺Sankt-peterburg, Sankt Petersburg, Russian Federation
Retina Vit Surgeons/Central NY
🇺🇸Liverpool, New York, United States
Retinal Diagnostic Center
🇺🇸Campbell, California, United States
The Retina Partners
🇺🇸Encino, California, United States
East Bay Retina Consultants
🇺🇸Oakland, California, United States
Colorado Retina Associates, PC
🇺🇸Lakewood, Colorado, United States
Retina Consultants of Southern Colorado PC
🇺🇸Colorado Springs, Colorado, United States
Florida Eye Associates
🇺🇸Melbourne, Florida, United States
Advanced Research
🇺🇸Deerfield Beach, Florida, United States
Rand Eye
🇺🇸Deerfield Beach, Florida, United States
Georgia Retina PC
🇺🇸Marietta, Georgia, United States
Retina Consultants of Hawaii
🇺🇸'Aiea, Hawaii, United States
Retina Vitreous Assoc of FL
🇺🇸Saint Petersburg, Florida, United States
Southeast Retina Center
🇺🇸Augusta, Georgia, United States
Northwestern Medical Group/Northwestern University
🇺🇸Chicago, Illinois, United States
Retina Associated Ltd
🇺🇸Elmhurst, Illinois, United States
University Retina and Macula Associates, PC
🇺🇸Oak Forest, Illinois, United States
Prairie Retina Center
🇺🇸Springfield, Illinois, United States
Johns Hopkins Med; Wilmer Eye Inst
🇺🇸Baltimore, Maryland, United States
Retina Associates
🇺🇸Lenexa, Kansas, United States
Retina Group of Washington
🇺🇸Chevy Chase, Maryland, United States
Cumberland Valley Retina PC
🇺🇸Hagerstown, Maryland, United States
Retina Assoc of Western NY
🇺🇸Rochester, New York, United States
Black Hills Eye Institute
🇺🇸Rapid City, South Dakota, United States
Palmetto Retina Center
🇺🇸West Columbia, South Carolina, United States
Retina Res Institute of Texas
🇺🇸Abilene, Texas, United States
Retina Consultants of Texas
🇺🇸The Woodlands, Texas, United States
Fundacion Zambrano
🇦🇷Caba, Argentina
Oftalmos
🇦🇷Capital Federal, Argentina
Centro Oftalmológico Dr. Charles S.A.
🇦🇷Capital Federal, Argentina
Hospital Italiano; Ophtalmology
🇦🇷Capital Federal, Argentina
Centro Oftalmólogos Especialistas
🇦🇷Rosario, Argentina
Strathfield Retina Clinic
🇦🇺Strathfield, New South Wales, Australia
Organizacion Medica de Investigacion
🇦🇷San Nicolás, Argentina
Eyeclinic Albury Wodonga
🇦🇺Albury, New South Wales, Australia
Save Sight Institute
🇦🇺Sydney, New South Wales, Australia
Centre For Eye Research Australia
🇦🇺East Melbourne, Victoria, Australia
Retina Specialists Victoria
🇦🇺Rowville, Victoria, Australia
The Lions Eye Institute
🇦🇺Nedlands, Western Australia, Australia
LKH-Univ.Klinikum Graz; Universitäts-Augenklinik
🇦🇹Graz, Austria
Hospital de Olhos de Aparecida - HOA
🇧🇷Aparecida de Goiania, GO, Brazil
Medizinische Universität Wien; Universitätsklinik für Augenheilkunde und Optometrie
🇦🇹Wien, Austria
Hospital das Clinicas - UFRGS
🇧🇷Porto Alegre, RS, Brazil
Botelho Hospital da Visao
🇧🇷Blumenau, SC, Brazil
West China Hospital, Sichuan University
🇨🇳Chengdu, China
The 2nd Affiliated Hospital of Harbin Medical University
🇨🇳Harbin, China
Shanghai Tenth People's Hospital
🇨🇳Shanghai, China
Tianjin Eye Hospital
🇨🇳Tianjin City, China
Hosp de Olhos de Sorocaba
🇧🇷Sorocaba, SP, Brazil
Universidade Federal de Sao Paulo - UNIFESP*X; Oftalmologia
🇧🇷Sao Paulo, SP, Brazil
Beijing Hospital of Ministry of Health
🇨🇳Beijing, China
Zhongshan Ophthalmic Center, Sun Yat-sen University
🇨🇳Guangzhou City, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou City, China
Shanghai First People's Hospital
🇨🇳Shanghai, China
The University of Hong Kong-Shenzhen Hospital; Local Ethic Committee
🇨🇳Shenzhen City, China
AXON Clinical
🇨🇿Prague, Czechia
He Eye Specialist Shenyang Hospital
🇨🇳Shenyang City, China
Renmin Hospital of Wuhan University
🇨🇳Wuhan, China
Henan Provincial Eye Hosptial
🇨🇳Zhengzhou, China
Tianjin Medical University Eye Hospital
🇨🇳Tianjin City, China
Chi De Creteil; Ophtalmologie
🇫🇷Creteil, France
Eye Hospital, Wenzhou Medical University
🇨🇳Wenzhou City, China
General Teaching Hospital Prague; Ophthalmology clinic
🇨🇿Prague, Czechia
Centre Ophtalmologique; Imagerie et laser
🇫🇷Paris, France
Hopital Lariboisiere; Ophtalmologie
🇫🇷Paris, France
Klinikum der Stadt Ludwigshafen am Rhein gGmbH; Augenklinik
🇩🇪Ludwigshafen, Germany
Universitätsklinikum Freiburg, Klinik für Augenheilkunde
🇩🇪Freiburg, Germany
Centres Ophtalmologique St Exupéry; Ophtalmologie
🇫🇷St Cyr Sur Loire, France
Queen Mary Hospital; Department of Ophthalmology
🇭🇰Hong Kong, Hong Kong
Debreceni Egyetem Klinikai Kozpont; Szemeszeti Klinika
🇭🇺Debrecen, Hungary
Zala Megyei Kórház; SZEMESZET
🇭🇺Zalaegerszeg, Hungary
Rabin MC; Ophtalmology
🇮🇱Petach Tikva, Israel
Fondazione G.B. Bietti Per Lo Studio E La Ricerca in Oftalmologia-Presidio Ospedaliero Britannico
🇮🇹Roma, Lazio, Italy
Irccs Ospedale San Raffaele;U.O. Oculistica
🇮🇹Milano, Lombardia, Italy
Aichi Medical University Hospital
🇯🇵Aichi, Japan
Hayashi Eye Hospital
🇯🇵Fukuoka, Japan
Asahikawa Medical University Hospital
🇯🇵Hokkaido, Japan
Hyogo Prefectural Amagasaki General Medical Center (Hyogo AGMC)
🇯🇵Hyogo, Japan
Kozawa eye hospital and diabetes center
🇯🇵Ibaraki, Japan
Kagawa University Hospital
🇯🇵Kagawa, Japan
Kagoshima University Hospital
🇯🇵Kagoshima, Japan
Shinshu University Hospital
🇯🇵Nagano, Japan
Mie University Hospital
🇯🇵Mie, Japan
Osaka Metropolitan University Hospital
🇯🇵Osaka, Japan
Tokyo Women's Medical University Hospital
🇯🇵Tokyo, Japan
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Yeungnam University Medical Center
🇰🇷Daegu, Korea, Republic of
Kyung Hee University Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Kim's Eye Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Szpital sw. Lukasza
🇵🇱Bielsko-Biala, Poland
OFTALMIKA Sp. z o.o
🇵🇱Bydgoszcz, Poland
Specjalistyczny O?rodek Okulistyczny Oculomedica
🇵🇱Bydgoszcz, Poland
Optimum Profesorskie Centrum Okulistyki
🇵🇱Gda?sk, Poland
Szpital Specjalistyczny nr 1; Oddzial Okulistyki
🇵🇱Bytom, Poland
Poradnia Okulistyczna i Salon Optyczny w Gliwicach- PRYZMAT
🇵🇱Gliwice, Poland
SP ZOZ Szpital Uniwersytecki w Krakowie Oddzia? Kliniczny Okulistyki i Onkologii Okulistycznej
🇵🇱Krakow, Poland
Gabinet Okulistyczny Prof Edward Wylegala
🇵🇱Katowice, Poland
Centrum Medyczne Dietla 19 Sp. Z O.O.
🇵🇱Kraków, Poland
O?rodek Chirurgii Oka Prof. Zagórskiego Na??czów
🇵🇱Na??czów, Poland
Lens Clinic
🇵🇱Rybnik, Poland
Centrum Medyczne Pulawska SP. z o.o.
🇵🇱Piaseczno, Poland
Espaco Medico Coimbra
🇵🇹Coimbra, Portugal
Centro Hospitalar E Universitário de Coimbra EPE - Serviço Oftalmologia; Serviço Oftalmologia
🇵🇹Coimbra, Portugal
Caminomed
🇵🇱Tarnowskie Góry, Poland
Centrum Zdrowia MDM
🇵🇱Warszawa, Poland
Hospital de Santa Maria; Servico de Oftalmologia
🇵🇹Lisboa, Portugal
Clinic Optimed
🇷🇺UFA, Baskortostan, Russian Federation
Medical Military Academy n.a S.M.Kirov
🇷🇺St.Petersburg, Sankt Petersburg, Russian Federation
Tan Tock Seng Hospital; Ophthalmology Department
🇸🇬Singapore, Singapore
Singapore Eye Research Institute
🇸🇬Singapore, Singapore
Complejo Hospitalario de Navarra; Servicio de oftalmologia
🇪🇸Pamplona, Navarra, Spain
Hospital de Santa Creu I Sant Pau; Servicio de Oftalmologia
🇪🇸Barcelona, Spain
Centro de Oftalmologia Barraquer; Servicio Oftalmologia
🇪🇸Barcelona, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Majadahonda, Madrid, Spain
Hospital Universitario Rio Hortega; Servicio de Oftalmologia
🇪🇸Valladolid, Spain
Changhua Christian Hospital; Department of Ophthalmology
🇨🇳Changhua, Taiwan
Hospital Clinic de Barcelona; Consultas Externas Oftalmologia
🇪🇸Barcelona, Spain
Chang Gung Medical Foundation - Linkou; Ophthalmology
🇨🇳Taoyuan, Taiwan
Taipei Veterans General Hospital; Ophthalmology
🇨🇳Taipei, Taiwan
Birmingham Midland Eye Centre
🇬🇧Birmingham, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Belfast Health and Social Care Trust, ROYAL VICTORIA HOSPITAL
🇬🇧Belfast, United Kingdom
Opthalmology Research Office
🇬🇧Bradford, United Kingdom
Bristol Eye Hospital;Retinal Treatment and Research Unit
🇬🇧Bristol, United Kingdom
Central Middlesex Hospital
🇬🇧London, United Kingdom
Royal Liverpool University Hospital; St Paul's Clinical Eye Research Centre
🇬🇧Liverpool, United Kingdom
St James University Hospital
🇬🇧Leeds, United Kingdom
Royal Victoria Infirmary
🇬🇧Newcastle upon Tyne, United Kingdom
Maidstone and Tunbridge Wells NHS Trust
🇬🇧Maidstone, United Kingdom
Piedmont Eye Center
🇺🇸Lynchburg, Virginia, United States
Mid Atlantic Retina - Wills Eye Hospital
🇺🇸Philadelphia, Pennsylvania, United States
VitreoRetinal Surgery, PLLC.; DBA Retina Consultants of Minnesota
🇺🇸Edina, Minnesota, United States
Cincinnati Eye Institute
🇺🇸Cincinnati, Ohio, United States
California Eye Specialists Medical group Inc.
🇺🇸Pasadena, California, United States
Northern California Retina Vitreous Associates
🇺🇸Mountain View, California, United States
Retina Consultants, San Diego
🇺🇸Poway, California, United States
Retina Consultants of Orange County
🇺🇸Fullerton, California, United States
Charleston Neuroscience Institute
🇺🇸Ladson, South Carolina, United States
Charles Retina Institute
🇺🇸Germantown, Tennessee, United States
Long Is. Vitreoretinal Consult
🇺🇸Hauppauge, New York, United States
Cascade Medical Research Institute LLC
🇺🇸Springfield, Oregon, United States
Retina & Vitreous of Texas
🇺🇸Bellaire, Texas, United States
Grupo Laser Vision
🇦🇷Rosario, Argentina
Strategic Clinical Research Group, LLC
🇺🇸Willow Park, Texas, United States
The Second Hospital of Jilin University
🇨🇳Changchun, China
Internationale Innovative Ophthalmochirurgie GbR; c/o Makula-Netzhaut-Zentrum Breyer Kaymak Klabe
🇩🇪Düsseldorf-Oberkassel, Germany
Nagoya City University Hospital
🇯🇵Aichi, Japan
Hyogo Medical University Hospital
🇯🇵Hyogo, Japan
Fukushima Medical University Hospital
🇯🇵Miyagi, Japan
Tokyo Medical University Hachioji Medical Center
🇯🇵Tokyo, Japan
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
SPEKTRUM Osrodek Okulistyki Klinicznej
🇵🇱Wroclaw, Poland
FSBI ?Scientific Research Institute of Eye Diseases? of Russian Academy of medical Sciences
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
Hospital Universitario de Bellvitge
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
West Coast Retina Medical Group
🇺🇸San Francisco, California, United States
Retina Associates of Florida, LLC
🇺🇸Tampa, Florida, United States
Retina Northwest
🇺🇸Portland, Oregon, United States
Retinal Research Institute, LLC
🇺🇸Phoenix, Arizona, United States
Tennessee Retina PC
🇺🇸Nashville, Tennessee, United States
Austin Retina Associates
🇺🇸Austin, Texas, United States
Austin Clinical Research LLC
🇺🇸Austin, Texas, United States
Retina Associates of Utah, PLLC
🇺🇸Salt Lake City, Utah, United States
Hong Kong Eye Hospital; CUHK Eye Centre
🇭🇰Mongkok, Hong Kong