AVENUE: A Proof-of-Concept Study of Faricimab (RO6867461) in Participants With Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (AMD)
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02484690
Collaborator
(none)
273
52
5
25.5
5.3
0.2
Study Details
Study Description
Brief Summary
This multiple-center, multiple-dose and regimen, randomized, double-masked active comparator-controlled, double-masked, five parallel group, 36-week study will evaluate the efficacy, safety, tolerability, and pharmacokinetics of faricimab (RO6867461) in participants with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).
The study was designed to allow the evaluation of RO6867461 in a treatment-naive population (comparison of Arms A, B, C, and D) and an anti-VEGF-incomplete responder population that met a predefined criterion at Week 12 (comparison between Arms A and E). Only one eye per participant was chosen as the study eye.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
273 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Multiple-Center, Multiple-Dose and Regimen, Randomized, Active Comparator Controlled, Double-Masked, Parallel Group, 36 Week Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RO6867461 Administered Intravitreally in Patients With Choroidal Neovascularization Secondary to Age-Related Macular Degeneration
Actual Study Start Date
:
Aug 11, 2015
Actual Primary Completion Date
:
Sep 26, 2017
Actual Study Completion Date
:
Sep 26, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) Participants will receive ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) Q4W up to Week 32 (total 9 injections). The final study visit will take place at Week 36. |
Drug: Ranibizumab
Ranibizumab will be administered as per the regimen specified in the individual arm.
Other Names:
|
| Experimental: Arm B: Faricimab, 1.5 mg Q4W Participants will receive faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit will take place at Week 36. |
Drug: Faricimab
Faricimab will be administered as per the regimen specified in the individual arm.
Other Names:
|
| Experimental: Arm C: Faricimab, 6 mg Q4W Participants will receive faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit will take place at Week 36. |
Drug: Faricimab
Faricimab will be administered as per the regimen specified in the individual arm.
Other Names:
|
| Experimental: Arm D: Faricimab, 6 mg Every 4-8 weeks Participants will receive faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit will take place at Week 36. |
Drug: Faricimab
Faricimab will be administered as per the regimen specified in the individual arm.
Other Names:
Drug: 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 treatment arm D at applicable visits to maintain masking.
|
| Experimental: Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W Participants will receive ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit will take place at Week 36. |
Drug: Faricimab
Faricimab will be administered as per the regimen specified in the individual arm.
Other Names:
Drug: Ranibizumab
Ranibizumab will be administered as per the regimen specified in the individual arm.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Mean Change From Baseline in BCVA Letter Score at Week 36, in Treatment-Naive Participants [Baseline, Week 36]
Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The primary analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.
- Mean Change From Week 12 in BCVA Letter Score at Week 36, in Anti-VEGF Incomplete Responders [Weeks 12 and 36]
Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The primary analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.
Secondary Outcome Measures
- Percentage of Participants Gaining Greater Than or Equal to (≥) 15 Letters From Baseline in BCVA Letter Score at Week 36, in Treatment-Naive Participants [Baseline, Week 36]
Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.
- Percentage of Participants Gaining ≥15 Letters From Week 12 in BCVA Letter Score at Week 36, in Anti-VEGF Incomplete Responders [Weeks 12 and 36]
Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. Missing values were not imputed; it was assumed that the data were missing at random.
- Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Week 36, in Treatment-Naive Participants [Week 36]
Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.
- Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Week 36, in Anti-VEGF Incomplete Responders [Week 36]
Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. Missing values were not imputed; it was assumed that the data were missing at random.
- Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Week 36, in Treatment-Naive Participants [Week 36]
Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.
- Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Week 36, in Anti-VEGF Incomplete Responders [Week 36]
Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. Missing values were not imputed; it was assumed that the data were missing at random.
- Mean Change From Baseline in Foveal Center Point Thickness at Week 36, as Measured by Spectral Domain Optical Coherence Tomography (SD-OCT), in Treatment-Naive Participants [Baseline, Week 36]
Foveal center point thickness (FCPT) is defined as the thickness from the inner limiting membrane to the retinal pigment epithelial at the horizontal slice closest to the center of the fovea. Foveal center point thickness was measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.
- Mean Change From Week 12 in Foveal Center Point Thickness at Week 36, as Measured by SD-OCT, in Anti-VEGF Incomplete Responders [Weeks 12 and 36]
Foveal center point thickness (FCPT) is defined as the thickness from the inner limiting membrane to the retinal pigment epithelial at the horizontal slice closest to the center of the fovea. Foveal center point thickness was measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.
- Mean Change From Baseline in Central Subfield Thickness at Week 36, as Measured by SD-OCT, in Treatment-Naive Participants [Baseline, Week 36]
Central subfield thickness (CST) is defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield. Central subfield thickness was measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.
- Mean Change From Week 12 in Central Subfield Thickness at Week 36, as Measured by SD-OCT in Anti-VEGF Incomplete Responders [Weeks 12 and 36]
Central subfield thickness (CST) is defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield. Central subfield thickness was measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.
- Number of Participants With Resolution of Dry Retina at Week 36, Defined as Absence of Cysts, Intraretinal Fluid, Pigment Epithelial Detachment, or Subretinal Fluid as Measured by SD-OCT, in Treatment-Naive Participants [Baseline, Week 36]
The presence of cysts, intraretinal fluid, pigment epithelial detachment, or subretinal fluid, as per the study's dry retina definition, were evaluated as individual dry retina outcomes. Cysts were defined as the presence of cystoid space (fluid) in the retina. Intraretinal fluid was defined as the presence of fluid within the retina. Pigment epithelial detachment was defined as the presence of a detachment of the pigment epithelium from the Bruch's membrane. Subretinal fluid was defined as the presence of fluid between the retina and the retinal pigment epithelium. All parameters were measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center.
- Number of Participants With Resolution of Dry Retina at Week 36, Defined as Absence of Cysts, Intraretinal Fluid, Pigment Epithelial Detachment, or Subretinal Fluid as Measured by SD-OCT, in Anti-VEGF Incomplete Responders [Weeks 12 and 36]
The presence of cysts, intraretinal fluid, pigment epithelial detachment, or subretinal fluid, as per the study's dry retina definition, were evaluated as individual dry retina outcomes. Cysts were defined as the presence of cystoid space (fluid) in the retina. Intraretinal fluid was defined as the presence of fluid within the retina. Pigment epithelial detachment was defined as the presence of a detachment of the pigment epithelium from the Bruch's membrane. Subretinal fluid was defined as the presence of fluid between the retina and the retinal pigment epithelium. All parameters were measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center.
- Mean Change From Baseline in Total Area of Choroidal Neovascularization (CNV) at Week 36, as Measured by Fundus Fluorescein Angiography (FFA), in Treatment-Naive Participants [Baseline, Week 36]
The total area of choroidal neovascularization (CNV) was evaluated by a central reading center using fundus fluorescein angiography (FFA). This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.
- Mean Change From Week 12 in Total Area of Choroidal Neovascularization (CNV) at Week 36, as Measured by FFA, in Anti-VEGF Incomplete Responders [Weeks 12 and 36]
The total area of choroidal neovascularization (CNV) was evaluated by a central reading center using fundus fluorescein angiography (FFA).
- Mean Change From Baseline in Total Area of Choroidal Neovascularization (CNV) Component at Week 36, as Measured by FFA, in Treatment-Naive Participants [Baseline, Week 36]
The total area of choroidal neovascularization (CNV) component (i.e., total area of CNV membrane) was evaluated by a central reading center using fundus fluorescein angiography (FFA). This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.
- Mean Change From Week 12 in Total Area of Choroidal Neovascularization (CNV) Component at Week 36, as Measured by FFA, in Anti-VEGF Incomplete Responders [Weeks 12 and 36]
The total area of choroidal neovascularization (CNV) component (i.e., total area of CNV membrane) was evaluated by a central reading center using fundus fluorescein angiography (FFA).
- Mean Change From Baseline in Total Area of Leakage at Week 36, as Measured by FFA, in Treatment-Naive Participants [Baseline, Week 36]
The total area of leakage was evaluated by a central reading center using fundus fluorescein angiography (FFA). This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.
- Mean Change From Week 12 in Total Area of Leakage at Week 36, as Measured by FFA, in Anti-VEGF Incomplete Responders [Weeks 12 and 36]
The total area of leakage was evaluated by a central reading center using fundus fluorescein angiography (FFA).
- Safety Summary of the Overall Number of Participants With at Least One Adverse Event by Event Type, in All Participants [From Baseline until 28 days after the last dose of study treatment (up to 36 weeks)]
This safety summary reports the number and percentage of participants who experienced at least one adverse event (AE) during the study. AEs are categorized as any AEs, ocular AEs occurring in the study eye or fellow eye, systemic AEs, serious AEs, AEs related to treatment with study drug, AEs leading to discontinuation (withdrawal) of treatment with study drug, and AEs with fatal outcome. The investigator independently assessed the seriousness and severity for each AE. Severity was graded according to the following grading scale: Mild = Discomfort noticed, but no disruption of normal daily activity; Moderate = Discomfort sufficient to reduce or affect normal daily activity; Severe = Incapacitating with inability to work or to perform normal daily activity. Severity and seriousness are not synonymous; regardless of severity, some AEs may have also met seriousness criteria.
- Number of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye by Highest Intensity, in All Participants [From Baseline until 28 days after the last dose of study treatment (up to 36 weeks)]
The investigator assessed adverse event severity according to the following grading scale: Mild = Discomfort noticed, but no disruption of normal daily activity; Moderate = Discomfort sufficient to reduce or affect normal daily activity; Severe = Incapacitating with inability to work or to perform normal daily activity. Only the most severe intensity was counted for multiple occurrences of the same adverse event per participant at the preferred term level. Severity and seriousness are not synonymous; regardless of severity, some adverse events may have also met seriousness criteria.
- Number of Participants With at Least One Systemic Adverse Event by Highest Intensity, in All Participants [From Baseline until 28 days after the last dose of study treatment (up to 36 weeks)]
The investigator assessed adverse event severity according to the following grading scale: Mild = Discomfort noticed, but no disruption of normal daily activity; Moderate = Discomfort sufficient to reduce or affect normal daily activity; Severe = Incapacitating with inability to work or to perform normal daily activity. Only the most severe intensity was counted for multiple occurrences of the same adverse event per participant at the preferred term level. Severity and seriousness are not synonymous; regardless of severity, some adverse events may have also met seriousness criteria.
- Number of Participants With Abnormal Systolic Blood Pressure, in All Participants [Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)]
Abnormal systolic blood pressure (supine) was defined as any value outside of the standard reference range, from <70 (low) to >140 (high) millimetres of mercury (mmHg). Baseline was defined as the last non-missing predose assessment. Not every abnormal vital sign qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy.
- Number of Participants With Abnormal Diastolic Blood Pressure, in All Participants [Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)]
Abnormal diastolic blood pressure (supine) was defined as any value outside of the standard reference range, from <40 (low) to >90 (high) millimetres of mercury (mmHg). Baseline was defined as the last non-missing predose assessment. Not every abnormal vital sign qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy.
- Number of Participants With Abnormal Heart Rate, in All Participants [Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)]
Abnormal heart rate (supine) was defined as any value outside of the standard reference range, from <40 (low) to >100 (high) beats per minute. Baseline was defined as the last non-missing predose assessment. Not every abnormal vital sign qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy.
- Number of Participants With Abnormal Body Temperature, in All Participants [Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)]
Abnormal body temperature (supine) was defined as any value outside of the standard reference range, from <36.5 (low) to >37.5 (high) degrees Celsius. Baseline was defined as the last non-missing predose assessment. Not every abnormal vital sign qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy.
- Number of Participants With Marked Laboratory Abnormalities in Hematology and Coagulation Tests, in All Participants [Predose at Baseline, Weeks 12 and 36, and at Early Termination and Unscheduled Visits (up to 36 weeks)]
Clinical laboratory tests for hematology and coagulation parameters were performed and any marked abnormal values (High or Low) were based on Roche's predefined standard reference ranges. Marked laboratory abnormalities are presented according to COG3007 abnormality criteria: Single, Not Last = abnormality detected at a single assessment, but not at the last assessment; Last or Replicated = abnormality detected at the last assessment or replicated at one or more assessments. Not every laboratory abnormality qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. Abs. = absolute count; Corp. = corpuscular; Ery. = erythrocyte; INR = International Normalized Ratio
- Number of Participants With Marked Laboratory Abnormalities in Blood Chemistry Tests, in All Participants [Predose at Baseline, Weeks 12 and 36, and at Early Termination and Unscheduled Visits (up to 36 weeks)]
Clinical laboratory tests for blood chemistry parameters were performed and any marked abnormal values (High or Low) were based on Roche's predefined standard reference ranges. Marked laboratory abnormalities are presented according to COG3007 abnormality criteria: Single, Not Last = abnormality detected at a single assessment, but not at the last assessment; Last or Replicated = abnormality detected at the last assessment or replicated at one or more assessments. Not every laboratory abnormality qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. GGT = gamma-glutamyltransferase; SGOT/AST = serum glutamic oxaloacetic transaminase / aspartate aminotransferase; SGPT/ALT = serum glutamic pyruvic transaminase / alanine aminotransferase
- Mean Change From Baseline in Intraocular Pressure in the Study Eye Over Time, in All Participants [Baseline, 0.5 hours postdose on Day 1, predose and 0.5 hours postdose at Weeks 4, 8, 12, 16, 20, 24, 28, and 32, and at Weeks 1, 13, and 36]
Intraocular pressure is the fluid pressure inside the eye. The method used to measure intraocular pressure (e.g., Goldmann tonometry) for each participant was to be applied consistently by the investigator throughout the study. On the day of dosing, intraocular pressure was monitored at 30 minutes post-treatment administration, and if intraocular pressure was ≥30 mmHg in the study eye, it was reassessed at 1 hour post-treatment administration.
- Change From Baseline in the Number of Participants With Anti-Drug Antibodies to Faricimab at Any Post-Baseline Timepoint [Baseline, Predose (0 hour) on Days 1, 28, 84, 112, 168, and 252 or early termination (up to 36 weeks)]
Blood samples were obtained for measurement of anti-faricimab antibodies by a validated enzyme-linked immunosorbent assay (ELISA).
- Mean Plasma Concentration of Faricimab Over Time, in All Participants [Predose (on days when treatment was administered) at Baseline and Weeks 4, 12, 13, 16, 24, and 36]
Plasma concentrations of faricimab were measured by a specific validated enzyme-linked immunoabsorbent assay (ELISA) only from samples of participants randomized to receive faricimab. Baseline was defined as the last non-missing predose assessment. The lower limit of quantification (LLOQ) for the faricimab assay was 0.800 nanograms per millilitre (ng/mL). Values below the limit of quantification were imputed as LLOQ divided by 2.
- Mean Change From Baseline in Free Vascular Endothelial Growth Factor-A (VEGF-A) Plasma Concentrations Over Time, in All Participants [Baseline, Weeks 4, 12, 13, 16, 24, and 36]
The concentration of free VEGF was determined in plasma samples using an enzyme-linked immunosorbent assay (ELISA) method. The lower limit of quantification (LLOQ) of the assay was 15.6 picograms per millilitre (pg/mL). Plasma free VEGF concentrations below the limit of quantification were imputed as LLOQ divided by 2.
- Mean Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Concentrations Over Time, in All Participants [Baseline, Weeks 4, 12, 13, 16, 24, and 36]
Total Ang-2 concentrations were determined in plasma samples using an appropriate assay method. The lower limit of quantification (LLOQ) of the assay was 0.09 nanograms per millilitre (ng/mL). Plasma total Ang-2 concentrations below the limit of quantification were imputed as LLOQ divided by 2.
- Mean Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Concentrations Over Time, in All Participants [Baseline, Weeks 4, 12, 13, 16, 24, and 36]
Free Ang-2 concentrations were determined in plasma samples using an appropriate assay method. The lower limit of quantification (LLOQ) of the assay was 0.9 nanograms per millilitre (ng/mL). Plasma free Ang-2 concentrations below the limit of quantification were imputed as LLOQ divided by 2.
Eligibility Criteria
Criteria
Ages Eligible for Study:
50 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Treatment-naive with CNV secondary to AMD, with subfoveal CNV or juxtafoveal CNV with a subfoveal component related to the CNV activity by FFA or SD-OCT
-
Active CNV
Exclusion Criteria:
-
CNV due to causes other than AMD
-
Subretinal hemorrhage, fibrosis, or atrophy involving either the fovea or more than 50% of the total lesion area
-
Cataract surgery within 3 months of baseline, or any other previous intraocular surgery
-
Major illness or surgery within 1 month prior to Screening
-
Glycosylated hemoglobin (HbA1c) above 7.5%
-
Uncontrolled blood pressure
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Associated Retina Consultants | Phoenix | Arizona | United States | 85020 |
| 2 | Retinal Consultants of Arizona | Phoenix | Arizona | United States | 85053 |
| 3 | California Retina Consultants | Bakersfield | California | United States | 93309 |
| 4 | Retina-Vitreous Associates Medical Group | Beverly Hills | California | United States | 90211 |
| 5 | The Retina Partners | Encino | California | United States | 91436 |
| 6 | Retina Consultants, San Diego | Poway | California | United States | 92064 |
| 7 | Orange County Retina Med Group | Santa Ana | California | United States | 92705 |
| 8 | Bay Area Retina Associates | Walnut Creek | California | United States | 94598 |
| 9 | American Institute of Research | Whittier | California | United States | 90603 |
| 10 | Retina Consultants of Southern | Colorado Springs | Colorado | United States | 80909 |
| 11 | Colorado Retina Associates, PC | Golden | Colorado | United States | 80401 |
| 12 | New England Retina Associates | Hamden | Connecticut | United States | 06518 |
| 13 | Retina Health Center | Fort Myers | Florida | United States | 33907 |
| 14 | National Ophthalmic Research Institute | Fort Myers | Florida | United States | 33912 |
| 15 | Florida Eye Associates | Melbourne | Florida | United States | 32901 |
| 16 | Central Florida Retina | Orlando | Florida | United States | 32806 |
| 17 | Retina Care Specialists | Palm Beach Gardens | Florida | United States | 33410 |
| 18 | Retina Vitreous Assoc of FL | Saint Petersburg | Florida | United States | 33711 |
| 19 | Southern Vitreoretinal Assoc | Tallahassee | Florida | United States | 32308 |
| 20 | Southeast Retina Center | Augusta | Georgia | United States | 30909 |
| 21 | Georgia Retina PC | Marietta | Georgia | United States | 30060 |
| 22 | Midwest Eye Institute Northside | Indianapolis | Indiana | United States | 46290 |
| 23 | Paducah Retinal Center | Paducah | Kentucky | United States | 42001 |
| 24 | Retina Group of Washington | Chevy Chase | Maryland | United States | 20815 |
| 25 | National Retina Institute | Towson | Maryland | United States | 21204 |
| 26 | Vitreo-Retinal Associates, PC | Worcester | Massachusetts | United States | 01605 |
| 27 | Vitreoretinal Surgery | Edina | Minnesota | United States | 55435 |
| 28 | Retina Associates of NJ | Toms River | New Jersey | United States | 08755 |
| 29 | Eye Associates of New Mexico | Albuquerque | New Mexico | United States | 87102 |
| 30 | Long Is. Vitreoretinal Consult | Great Neck | New York | United States | 11021 |
| 31 | Opthalmic Consultants of LI | Lynbrook | New York | United States | 11563 |
| 32 | Retina Assoc of Western NY | Rochester | New York | United States | 14620 |
| 33 | The Retina Consultants | Slingerlands | New York | United States | 12159 |
| 34 | Western Carolina Retinal Associate PA | Asheville | North Carolina | United States | 28803 |
| 35 | Char Eye Ear &Throat Assoc | Charlotte | North Carolina | United States | 28210 |
| 36 | OSU Eye Physicians & Surgeons | Columbus | Ohio | United States | 43212 |
| 37 | Oregon Retina, LLP | Eugene | Oregon | United States | 97401 |
| 38 | Oregon Retina institute | Medford | Oregon | United States | 97504 |
| 39 | Retina Northwest | Portland | Oregon | United States | 97221 |
| 40 | Mid Atlantic Retina | Philadelphia | Pennsylvania | United States | 19107 |
| 41 | Palmetto Retina Center | West Columbia | South Carolina | United States | 29169 |
| 42 | Southeastern Retina Associates Chattanooga | Chattanooga | Tennessee | United States | 37421 |
| 43 | Charles Retina Institute | Germantown | Tennessee | United States | 38138 |
| 44 | Tennessee Retina PC. | Nashville | Tennessee | United States | 37203 |
| 45 | W Texas Retina Consultants PA | Abilene | Texas | United States | 79606 |
| 46 | Austin Retina Associates | Austin | Texas | United States | 78705 |
| 47 | Retina Research Center | Austin | Texas | United States | 78705 |
| 48 | Retina Consultants of Houston | Houston | Texas | United States | 77030 |
| 49 | Strategic Clinical Research Group, LLC | Willow Park | Texas | United States | 76087 |
| 50 | Retina Associates of Utah | Salt Lake City | Utah | United States | 84107 |
| 51 | Univ of Virginia Ophthalmology | Charlottesville | Virginia | United States | 22903 |
| 52 | Spokane Eye Clinical Research | Spokane | Washington | United States | 99204 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02484690
Other Study ID Numbers:
- BP29647
First Posted:
Jun 30, 2015
Last Update Posted:
Nov 12, 2020
Last Verified:
Oct 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 273 patients were randomized, but 10 participants in total were excluded from the analysis populations, 1, 3, 1, and 5 from Arms B, C, D, and E, respectively, because of Good Clinical Practice (GCP) violations at a single site. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Period Title: Overall Study | |||||
| STARTED | 68 | 46 | 39 | 46 | 64 |
| Received at Least One Dose of Study Drug | 67 | 46 | 39 | 46 | 64 |
| COMPLETED | 64 | 40 | 36 | 44 | 58 |
| NOT COMPLETED | 4 | 6 | 3 | 2 | 6 |
Baseline Characteristics
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. | Total of all reporting groups |
| Overall Participants | 68 | 46 | 39 | 46 | 64 | 263 |
| Age (Years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [Years] |
76.4
(8.9)
|
78.2
(8.9)
|
78.0
(9.1)
|
80.0
(8.0)
|
79.2
(8.3)
|
78.3
(8.7)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
39
57.4%
|
32
69.6%
|
27
69.2%
|
34
73.9%
|
40
62.5%
|
172
65.4%
|
| Male |
29
42.6%
|
14
30.4%
|
12
30.8%
|
12
26.1%
|
24
37.5%
|
91
34.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
4
5.9%
|
3
6.5%
|
0
0%
|
4
8.7%
|
2
3.1%
|
13
4.9%
|
| Not Hispanic or Latino |
64
94.1%
|
43
93.5%
|
38
97.4%
|
42
91.3%
|
61
95.3%
|
248
94.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
1
2.6%
|
0
0%
|
1
1.6%
|
2
0.8%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
0
0%
|
1
0.4%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.4%
|
| White |
66
97.1%
|
45
97.8%
|
39
100%
|
44
95.7%
|
64
100%
|
258
98.1%
|
| More than one race |
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.4%
|
| Unknown or Not Reported |
0
0%
|
1
2.2%
|
0
0%
|
1
2.2%
|
0
0%
|
2
0.8%
|
| Best-Corrected Visual Acuity (BCVA) Letter Score in the Study Eye at Baseline (BCVA Letters) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [BCVA Letters] |
55.2
(12.7)
|
56.7
(11.1)
|
56.2
(12.2)
|
56.3
(11.5)
|
55.7
(11.6)
|
55.9
(11.9)
|
| Best-Corrected Visual Acuity (BCVA) Letter Score Category in the Study Eye at Baseline (Count of Participants) | ||||||
| BCVA Letter Score ≤54 |
22
32.4%
|
20
43.5%
|
15
38.5%
|
21
45.7%
|
26
40.6%
|
104
39.5%
|
| BCVA Letter Score >54 |
45
66.2%
|
26
56.5%
|
24
61.5%
|
25
54.3%
|
38
59.4%
|
158
60.1%
|
| Assessment Missing |
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.4%
|
| Choroidal Neovascularization (CNV) Lesion Type in the Study Eye at Baseline (Count of Participants) | ||||||
| Classic & Occult CNV |
26
38.2%
|
19
41.3%
|
12
30.8%
|
20
43.5%
|
21
32.8%
|
98
37.3%
|
| Classic CNV |
8
11.8%
|
6
13%
|
7
17.9%
|
6
13%
|
10
15.6%
|
37
14.1%
|
| Occult CNV |
33
48.5%
|
20
43.5%
|
20
51.3%
|
19
41.3%
|
33
51.6%
|
125
47.5%
|
| Assessment Missing |
1
1.5%
|
1
2.2%
|
0
0%
|
1
2.2%
|
0
0%
|
3
1.1%
|
| Presence or Absence of Retinal Angiomatous Proliferation (RAP) in the Study Eye at Baseline (Count of Participants) | ||||||
| RAP Absent |
44
64.7%
|
30
65.2%
|
29
74.4%
|
29
63%
|
47
73.4%
|
179
68.1%
|
| RAP Present |
22
32.4%
|
14
30.4%
|
9
23.1%
|
14
30.4%
|
16
25%
|
75
28.5%
|
| Assessment Missing |
2
2.9%
|
2
4.3%
|
1
2.6%
|
3
6.5%
|
1
1.6%
|
9
3.4%
|
| Presence or Absence of Polypoidal Choroidal Vasculopathy (PCV) in the Study Eye at Baseline (Count of Participants) | ||||||
| PCV Absent |
61
89.7%
|
42
91.3%
|
36
92.3%
|
40
87%
|
57
89.1%
|
236
89.7%
|
| PCV Present |
7
10.3%
|
3
6.5%
|
3
7.7%
|
5
10.9%
|
7
10.9%
|
25
9.5%
|
| Assessment Missing |
0
0%
|
1
2.2%
|
0
0%
|
1
2.2%
|
0
0%
|
2
0.8%
|
Outcome Measures
| Title | Mean Change From Baseline in BCVA Letter Score at Week 36, in Treatment-Naive Participants |
|---|---|
| Description | Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The primary analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism. |
| Time Frame | Baseline, Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treatment-naive participants randomized to Arms A, B, C, and D. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. |
| Measure Participants | 68 | 46 | 39 | 46 |
| Least Squares Mean (80% Confidence Interval) [BCVA Letters] |
7.61
|
9.18
|
6.02
|
6.10
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm B) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm B mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5244 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: BCVA at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 1.57 | |
| Confidence Interval |
(2-Sided) 80% -1.60 to 4.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm C: Faricimab, 6 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm C) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm C mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5308 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: BCVA at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -1.59 | |
| Confidence Interval |
(2-Sided) 80% -4.86 to 1.67 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm C minus Arm A. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm D) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm D mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5309 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: BCVA at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -1.51 | |
| Confidence Interval |
(2-Sided) 80% -4.62 to 1.59 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm D minus Arm A. | |
| Title | Mean Change From Week 12 in BCVA Letter Score at Week 36, in Anti-VEGF Incomplete Responders |
|---|---|
| Description | Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The primary analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism. |
| Time Frame | Weeks 12 and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Anti-VEGF incomplete responders, which consisted of participants randomized to Arms A and E with BCVA ≤68 at Week 12 with at least one letter improvement relative to Baseline. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 37 | 38 |
| Least Squares Mean (80% Confidence Interval) [BCVA Letters] |
1.72
|
0.04
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm E) and the control group (Arm A). The alternative hypothesis (Ha) was that the Arm E mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3034 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: BCVA at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -1.68 | |
| Confidence Interval |
(2-Sided) 80% -3.77 to 0.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm E minus Arm A. | |
| Title | Percentage of Participants Gaining Greater Than or Equal to (≥) 15 Letters From Baseline in BCVA Letter Score at Week 36, in Treatment-Naive Participants |
|---|---|
| Description | Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random. |
| Time Frame | Baseline, Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treatment-naive participants randomized to Arms A, B, C, and D. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. |
| Measure Participants | 68 | 46 | 39 | 46 |
| Least Squares Mean (80% Confidence Interval) [Percentage of Participants] |
31.0
45.6%
|
36.6
79.6%
|
27.9
71.5%
|
23.7
51.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm B) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm B mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5527 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction. An AR(1) covariance structure was also used. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 5.63 | |
| Confidence Interval |
(2-Sided) 80% -6.52 to 17.77 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm C: Faricimab, 6 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm C) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm C mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7382 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction. An AR(1) covariance structure was also used. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -3.09 | |
| Confidence Interval |
(2-Sided) 80% -14.95 to 8.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm C minus Arm A. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm D) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm D mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3932 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction. An AR(1) covariance structure was also used. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -7.32 | |
| Confidence Interval |
(2-Sided) 80% -18.32 to 3.67 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm D minus Arm A. | |
| Title | Percentage of Participants Gaining ≥15 Letters From Week 12 in BCVA Letter Score at Week 36, in Anti-VEGF Incomplete Responders |
|---|---|
| Description | Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. Missing values were not imputed; it was assumed that the data were missing at random. |
| Time Frame | Weeks 12 and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Anti-VEGF incomplete responders, which consisted of participants randomized to Arms A and E with BCVA ≤68 at Week 12 with at least one letter improvement relative to Baseline. This analysis only included participants with non-missing assessments at Weeks 12 and 36. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 35 | 37 |
| Number (80% Confidence Interval) [Percentage of Participants] |
5.71
8.4%
|
0.00
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference between the treatment group (Arm E) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm E was different from Arm A. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2328 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage of Participants |
| Estimated Value | -5.71 | |
| Confidence Interval |
(2-Sided) 80% -10.74 to -0.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The difference was calculated as Arm E minus Arm A. | |
| Title | Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Week 36, in Treatment-Naive Participants |
|---|---|
| Description | Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random. |
| Time Frame | Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treatment-naive participants randomized to Arms A, B, C, and D. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. |
| Measure Participants | 68 | 46 | 39 | 46 |
| Least Squares Mean (80% Confidence Interval) [Percentage of Participants] |
49.5
72.8%
|
49.0
106.5%
|
39.4
101%
|
41.8
90.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm B) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm B mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9581 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction. An AR(1) covariance structure was also used. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -0.52 | |
| Confidence Interval |
(2-Sided) 80% -13.26 to 12.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm C: Faricimab, 6 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm C) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm C mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3166 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction. An AR(1) covariance structure was also used. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -10.08 | |
| Confidence Interval |
(2-Sided) 80% -22.99 to 2.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm C minus Arm A. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm D) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm D mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4244 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction. An AR(1) covariance structure was also used. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -7.68 | |
| Confidence Interval |
(2-Sided) 80% -20.01 to 4.64 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm D minus Arm A. | |
| Title | Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Week 36, in Anti-VEGF Incomplete Responders |
|---|---|
| Description | Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. Missing values were not imputed; it was assumed that the data were missing at random. |
| Time Frame | Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Anti-VEGF incomplete responders, which consisted of participants randomized to Arms A and E with BCVA ≤68 at Week 12 with at least one letter improvement relative to Baseline. This analysis only included participants with non-missing assessments at Week 36. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 35 | 37 |
| Number (80% Confidence Interval) [Percentage of Participants] |
22.86
33.6%
|
16.22
35.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference between the treatment group (Arm E) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm E was different from Arm A. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5586 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage of Participants |
| Estimated Value | -6.64 | |
| Confidence Interval |
(2-Sided) 80% -18.60 to 5.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The difference was calculated as Arm E minus Arm A. | |
| Title | Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Week 36, in Treatment-Naive Participants |
|---|---|
| Description | Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random. |
| Time Frame | Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treatment-naive participants randomized to Arms A, B, C, and D. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. |
| Measure Participants | 68 | 46 | 39 | 46 |
| Least Squares Mean (80% Confidence Interval) [Percentage of Participants] |
7.7
11.3%
|
8.7
18.9%
|
15.8
40.5%
|
8.8
19.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm B) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm B mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8536 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction. An AR(1) covariance structure was also used. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 1.00 | |
| Confidence Interval |
(2-Sided) 80% -5.93 to 7.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm C: Faricimab, 6 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm C) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm C mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2303 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction. An AR(1) covariance structure was also used. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 8.14 | |
| Confidence Interval |
(2-Sided) 80% -0.56 to 16.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm C minus Arm A. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm D) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm D mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8406 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction. An AR(1) covariance structure was also used. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 1.08 | |
| Confidence Interval |
(2-Sided) 80% -5.79 to 7.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm D minus Arm A. | |
| Title | Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Week 36, in Anti-VEGF Incomplete Responders |
|---|---|
| Description | Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. Missing values were not imputed; it was assumed that the data were missing at random. |
| Time Frame | Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Anti-VEGF incomplete responders, which consisted of participants randomized to Arms A and E with BCVA ≤68 at Week 12 with at least one letter improvement relative to Baseline. This analysis only included participants with non-missing assessments at Week 36. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 35 | 37 |
| Number (80% Confidence Interval) [Percentage of Participants] |
14.29
21%
|
13.51
29.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference between the treatment group (Arm E) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm E was different from Arm A. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage of Participants |
| Estimated Value | -0.77 | |
| Confidence Interval |
(2-Sided) 80% -11.23 to 9.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The difference was calculated as Arm E minus Arm A. | |
| Title | Mean Change From Baseline in Foveal Center Point Thickness at Week 36, as Measured by Spectral Domain Optical Coherence Tomography (SD-OCT), in Treatment-Naive Participants |
|---|---|
| Description | Foveal center point thickness (FCPT) is defined as the thickness from the inner limiting membrane to the retinal pigment epithelial at the horizontal slice closest to the center of the fovea. Foveal center point thickness was measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism. |
| Time Frame | Baseline, Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treatment-naive participants randomized to Arms A, B, C, and D. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. |
| Measure Participants | 68 | 46 | 39 | 46 |
| Least Squares Mean (80% Confidence Interval) [micrometres (μm)] |
-194.00
|
-181.35
|
-193.12
|
-161.20
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm B) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm B mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3798 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: FCPT at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 12.65 | |
| Confidence Interval |
(2-Sided) 80% -5.81 to 31.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm C: Faricimab, 6 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm C) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm C mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9529 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: FCPT at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 0.88 | |
| Confidence Interval |
(2-Sided) 80% -18.3 to 20.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm C minus Arm A. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm D) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm D mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0208 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: FCPT at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 32.81 | |
| Confidence Interval |
(2-Sided) 80% 14.65 to 50.96 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm D minus Arm A. | |
| Title | Mean Change From Week 12 in Foveal Center Point Thickness at Week 36, as Measured by SD-OCT, in Anti-VEGF Incomplete Responders |
|---|---|
| Description | Foveal center point thickness (FCPT) is defined as the thickness from the inner limiting membrane to the retinal pigment epithelial at the horizontal slice closest to the center of the fovea. Foveal center point thickness was measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism. |
| Time Frame | Weeks 12 and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Anti-VEGF incomplete responders, which consisted of participants randomized to Arms A and E with BCVA ≤68 at Week 12 with at least one letter improvement relative to Baseline. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 37 | 38 |
| Least Squares Mean (80% Confidence Interval) [micrometres (μm)] |
-14.5
|
-20.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference between the treatment group (Arm E) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm E was different from Arm A. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5185 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: FCPT at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -6.35 | |
| Confidence Interval |
(2-Sided) 80% -19.0 to 6.27 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm E minus Arm A. | |
| Title | Mean Change From Baseline in Central Subfield Thickness at Week 36, as Measured by SD-OCT, in Treatment-Naive Participants |
|---|---|
| Description | Central subfield thickness (CST) is defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield. Central subfield thickness was measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism. |
| Time Frame | Baseline, Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treatment-naive participants randomized to Arms A, B, C, and D. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. |
| Measure Participants | 68 | 46 | 39 | 46 |
| Least Squares Mean (80% Confidence Interval) [micrometres (μm)] |
-176.18
|
-156.73
|
-173.40
|
-147.66
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm B) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm B mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1624 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: CST at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 19.45 | |
| Confidence Interval |
(2-Sided) 80% 1.61 to 37.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm C: Faricimab, 6 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm C) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm C mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8475 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: CST at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 2.79 | |
| Confidence Interval |
(2-Sided) 80% -15.8 to 21.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm C minus Arm A. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm D) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm D mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0381 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: CST at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 28.52 | |
| Confidence Interval |
(2-Sided) 80% 10.93 to 46.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm D minus Arm A. | |
| Title | Mean Change From Week 12 in Central Subfield Thickness at Week 36, as Measured by SD-OCT in Anti-VEGF Incomplete Responders |
|---|---|
| Description | Central subfield thickness (CST) is defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield. Central subfield thickness was measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism. |
| Time Frame | Weeks 12 and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Anti-VEGF incomplete responders, which consisted of participants randomized to Arms A and E with BCVA ≤68 at Week 12 with at least one letter improvement relative to Baseline. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 37 | 38 |
| Least Squares Mean (80% Confidence Interval) [micrometres (μm)] |
-17.00
|
-31.42
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference between the treatment group (Arm E) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm E was different from Arm A. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2089 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: CST at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -14.4 | |
| Confidence Interval |
(2-Sided) 80% -29.1 to 0.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm E minus Arm A. | |
| Title | Number of Participants With Resolution of Dry Retina at Week 36, Defined as Absence of Cysts, Intraretinal Fluid, Pigment Epithelial Detachment, or Subretinal Fluid as Measured by SD-OCT, in Treatment-Naive Participants |
|---|---|
| Description | The presence of cysts, intraretinal fluid, pigment epithelial detachment, or subretinal fluid, as per the study's dry retina definition, were evaluated as individual dry retina outcomes. Cysts were defined as the presence of cystoid space (fluid) in the retina. Intraretinal fluid was defined as the presence of fluid within the retina. Pigment epithelial detachment was defined as the presence of a detachment of the pigment epithelium from the Bruch's membrane. Subretinal fluid was defined as the presence of fluid between the retina and the retinal pigment epithelium. All parameters were measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. |
| Time Frame | Baseline, Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treatment-naive participants randomized to Arms A, B, C, and D. This analysis only included participants with presence of the individual dry retina measures (cysts, intraretinal fluid, pigment epithelial detachment, or subretinal fluid) at Baseline and who were reassessed at Week 36. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. |
| Measure Participants | 68 | 46 | 39 | 46 |
| Cysts: Present at Baseline |
52
76.5%
|
29
63%
|
29
74.4%
|
38
82.6%
|
| Cysts: Present at Week 36 |
13
19.1%
|
7
15.2%
|
6
15.4%
|
11
23.9%
|
| Cysts: Absent at Week 36 |
36
52.9%
|
18
39.1%
|
21
53.8%
|
25
54.3%
|
| Intraretinal Fluid: Present at Baseline |
67
98.5%
|
46
100%
|
39
100%
|
45
97.8%
|
| Intraretinal Fluid: Present at Week 36 |
46
67.6%
|
27
58.7%
|
28
71.8%
|
34
73.9%
|
| Intraretinal Fluid: Absent at Week 36 |
18
26.5%
|
13
28.3%
|
9
23.1%
|
9
19.6%
|
| Pigment Epithelial Detachment: Present at Baseline |
58
85.3%
|
37
80.4%
|
27
69.2%
|
36
78.3%
|
| Pigment Epithelial Detachment: Present at Week 36 |
43
63.2%
|
25
54.3%
|
20
51.3%
|
32
69.6%
|
| Pigment Epithelial Detachment: Absent at Week 36 |
12
17.6%
|
6
13%
|
6
15.4%
|
4
8.7%
|
| Subretinal Fluid: Present at Baseline |
56
82.4%
|
41
89.1%
|
30
76.9%
|
35
76.1%
|
| Subretinal Fluid: Present at Week 36 |
11
16.2%
|
18
39.1%
|
3
7.7%
|
8
17.4%
|
| Subretinal Fluid: Absent at Week 36 |
42
61.8%
|
18
39.1%
|
26
66.7%
|
25
54.3%
|
| Title | Number of Participants With Resolution of Dry Retina at Week 36, Defined as Absence of Cysts, Intraretinal Fluid, Pigment Epithelial Detachment, or Subretinal Fluid as Measured by SD-OCT, in Anti-VEGF Incomplete Responders |
|---|---|
| Description | The presence of cysts, intraretinal fluid, pigment epithelial detachment, or subretinal fluid, as per the study's dry retina definition, were evaluated as individual dry retina outcomes. Cysts were defined as the presence of cystoid space (fluid) in the retina. Intraretinal fluid was defined as the presence of fluid within the retina. Pigment epithelial detachment was defined as the presence of a detachment of the pigment epithelium from the Bruch's membrane. Subretinal fluid was defined as the presence of fluid between the retina and the retinal pigment epithelium. All parameters were measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. |
| Time Frame | Weeks 12 and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Anti-VEGF incomplete responders, consisting of participants randomized to Arms A and E with BCVA ≤68 at Week 12 with ≥1 letter increase from Baseline. Analysis only included those with presence of individual dry retina measures (cysts, intraretinal fluid, pigment epithelial detachment, or subretinal fluid) at Week 12 and reassessed at Week 36. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 37 | 38 |
| Cysts: Present at Week 12 |
9
13.2%
|
11
23.9%
|
| Cysts: Present at Week 36 |
4
5.9%
|
5
10.9%
|
| Cysts: Absent at Week 36 |
5
7.4%
|
6
13%
|
| Intraretinal Fluid: Present at Week 12 |
28
41.2%
|
36
78.3%
|
| Intraretinal Fluid: Present at Week 36 |
19
27.9%
|
28
60.9%
|
| Intraretinal Fluid: Absent at Week 36 |
7
10.3%
|
7
15.2%
|
| Pigment Epithelial Detachment: Present at Week 12 |
24
35.3%
|
28
60.9%
|
| Pigment Epithelial Detachment: Present at Week 36 |
19
27.9%
|
22
47.8%
|
| Pigment Epithelial Detachment: Absent at Week 36 |
3
4.4%
|
5
10.9%
|
| Subretinal Fluid: Present at Week 12 |
10
14.7%
|
9
19.6%
|
| Subretinal Fluid: Present at Week 36 |
3
4.4%
|
2
4.3%
|
| Subretinal Fluid: Absent at Week 36 |
5
7.4%
|
6
13%
|
| Title | Mean Change From Baseline in Total Area of Choroidal Neovascularization (CNV) at Week 36, as Measured by Fundus Fluorescein Angiography (FFA), in Treatment-Naive Participants |
|---|---|
| Description | The total area of choroidal neovascularization (CNV) was evaluated by a central reading center using fundus fluorescein angiography (FFA). This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism. |
| Time Frame | Baseline, Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treatment-naive participants randomized to Arms A, B, C, and D. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. |
| Measure Participants | 68 | 46 | 39 | 46 |
| Least Squares Mean (80% Confidence Interval) [millimetres squared (mm^2)] |
-3.41
|
-3.81
|
-3.19
|
-3.31
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm B) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm B mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6717 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: CNV at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -0.40 | |
| Confidence Interval |
(2-Sided) 80% -1.61 to 0.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm C: Faricimab, 6 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm C) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm C mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8131 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: CNV at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 0.23 | |
| Confidence Interval |
(2-Sided) 80% -1.01 to 1.47 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm C minus Arm A. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between each of the treatment groups (Arms B, C, or D) and the control group (Arm A). The alternative hypothesis (Ha) was that Arms B, C, or D means were different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9069 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: CNV at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 0.11 | |
| Confidence Interval |
(2-Sided) 80% -1.07 to 1.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm D minus Arm A. | |
| Title | Mean Change From Week 12 in Total Area of Choroidal Neovascularization (CNV) at Week 36, as Measured by FFA, in Anti-VEGF Incomplete Responders |
|---|---|
| Description | The total area of choroidal neovascularization (CNV) was evaluated by a central reading center using fundus fluorescein angiography (FFA). |
| Time Frame | Weeks 12 and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Anti-VEGF incomplete responders, which consisted of participants randomized to Arms A and E with BCVA ≤68 at Week 12 with at least one letter improvement relative to Baseline. This analysis only included participants with non-missing assessments at Weeks 12 and 36. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 22 | 21 |
| Mean (Standard Deviation) [millimetres squared (mm^2)] |
-0.50
(2.37)
|
-1.37
(3.72)
|
| Title | Mean Change From Baseline in Total Area of Choroidal Neovascularization (CNV) Component at Week 36, as Measured by FFA, in Treatment-Naive Participants |
|---|---|
| Description | The total area of choroidal neovascularization (CNV) component (i.e., total area of CNV membrane) was evaluated by a central reading center using fundus fluorescein angiography (FFA). This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism. |
| Time Frame | Baseline, Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treatment-naive participants randomized to Arms A, B, C, and D. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. |
| Measure Participants | 68 | 46 | 39 | 46 |
| Least Squares Mean (80% Confidence Interval) [millimetres squared (mm^2)] |
-4.18
|
-5.14
|
-2.96
|
-3.83
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm B) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm B mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3189 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: CNV at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -0.96 | |
| Confidence Interval |
(2-Sided) 80% -2.20 to 0.28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm C: Faricimab, 6 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm C) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm C mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2256 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: CNV at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 1.22 | |
| Confidence Interval |
(2-Sided) 80% -0.07 to 2.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm C minus Arm A. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm D) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm D mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7086 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: CNV at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 0.35 | |
| Confidence Interval |
(2-Sided) 80% -0.86 to 1.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm D minus Arm A. | |
| Title | Mean Change From Week 12 in Total Area of Choroidal Neovascularization (CNV) Component at Week 36, as Measured by FFA, in Anti-VEGF Incomplete Responders |
|---|---|
| Description | The total area of choroidal neovascularization (CNV) component (i.e., total area of CNV membrane) was evaluated by a central reading center using fundus fluorescein angiography (FFA). |
| Time Frame | Weeks 12 and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Anti-VEGF incomplete responders, which consisted of participants randomized to Arms A and E with BCVA ≤68 at Week 12 with at least one letter improvement relative to Baseline. This analysis only included participants with non-missing assessments at Weeks 12 and 36. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 22 | 21 |
| Mean (Standard Deviation) [millimetres squared (mm^2)] |
-1.87
(4.05)
|
-1.88
(3.98)
|
| Title | Mean Change From Baseline in Total Area of Leakage at Week 36, as Measured by FFA, in Treatment-Naive Participants |
|---|---|
| Description | The total area of leakage was evaluated by a central reading center using fundus fluorescein angiography (FFA). This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism. |
| Time Frame | Baseline, Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treatment-naive participants randomized to Arms A, B, C, and D. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. |
| Measure Participants | 68 | 46 | 39 | 46 |
| Least Squares Mean (80% Confidence Interval) [millimetres squared (mm^2)] |
-5.15
|
-5.94
|
-3.71
|
-4.66
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm B: Faricimab, 1.5 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm B) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm B mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4353 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: leak at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -0.78 | |
| Confidence Interval |
(2-Sided) 80% -2.07 to 0.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm C: Faricimab, 6 mg Q4W |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm C) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm C mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1652 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: leak at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 1.45 | |
| Confidence Interval |
(2-Sided) 80% 0.11 to 2.78 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm C minus Arm A. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W), Arm D: Faricimab, 6 mg Every 4-8 Weeks |
|---|---|---|
| Comments | The null hypothesis (Ho) was that there was no difference in means between the treatment group (Arm D) and the control group (Arm A). The alternative hypothesis (Ha) was that Arm D mean was different from Arm A mean. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.61111 |
| Comments | The threshold for statistical significance was an unadjusted 2-sided p-value <0.2. There was no formal correction for multiple comparisons. | |
| Method | Mixed Model for Repeated Measures | |
| Comments | Categorical covariates(cov): RAP/PCV at baseline(BL), treatment group, visit, & visit by treatment group; Continuous cov: leak at BL; Unstructured cov | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 0.50 | |
| Confidence Interval |
(2-Sided) 80% -0.76 to 1.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference was calculated as Arm D minus Arm A. | |
| Title | Mean Change From Week 12 in Total Area of Leakage at Week 36, as Measured by FFA, in Anti-VEGF Incomplete Responders |
|---|---|
| Description | The total area of leakage was evaluated by a central reading center using fundus fluorescein angiography (FFA). |
| Time Frame | Weeks 12 and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Anti-VEGF incomplete responders, which consisted of participants randomized to Arms A and E with BCVA ≤68 at Week 12 with at least one letter improvement relative to Baseline. This analysis only included participants with non-missing assessments at Weeks 12 and 36. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 22 | 21 |
| Mean (Standard Deviation) [millimetres squared (mm^2)] |
-1.87
(4.05)
|
-2.00
(3.98)
|
| Title | Safety Summary of the Overall Number of Participants With at Least One Adverse Event by Event Type, in All Participants |
|---|---|
| Description | This safety summary reports the number and percentage of participants who experienced at least one adverse event (AE) during the study. AEs are categorized as any AEs, ocular AEs occurring in the study eye or fellow eye, systemic AEs, serious AEs, AEs related to treatment with study drug, AEs leading to discontinuation (withdrawal) of treatment with study drug, and AEs with fatal outcome. The investigator independently assessed the seriousness and severity for each AE. Severity was graded according to the following grading scale: Mild = Discomfort noticed, but no disruption of normal daily activity; Moderate = Discomfort sufficient to reduce or affect normal daily activity; Severe = Incapacitating with inability to work or to perform normal daily activity. Severity and seriousness are not synonymous; regardless of severity, some AEs may have also met seriousness criteria. |
| Time Frame | From Baseline until 28 days after the last dose of study treatment (up to 36 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study treatment |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 67 | 46 | 39 | 46 | 64 |
| Any Adverse Event (AE) |
51
75%
|
39
84.8%
|
31
79.5%
|
39
84.8%
|
54
84.4%
|
| Ocular AE in Either Eye |
39
57.4%
|
25
54.3%
|
23
59%
|
29
63%
|
37
57.8%
|
| Ocular AE in the Study Eye |
28
41.2%
|
21
45.7%
|
21
53.8%
|
27
58.7%
|
28
43.8%
|
| Ocular AE in the Fellow Eye |
21
30.9%
|
16
34.8%
|
9
23.1%
|
18
39.1%
|
20
31.3%
|
| Serious Ocular AE in the Study Eye |
0
0%
|
3
6.5%
|
0
0%
|
0
0%
|
2
3.1%
|
| Ocular AE in Study Eye Leading to Withdrawal |
0
0%
|
1
2.2%
|
0
0%
|
0
0%
|
4
6.3%
|
| Systemic AE |
37
54.4%
|
37
80.4%
|
23
59%
|
30
65.2%
|
43
67.2%
|
| Serious Systemic AE |
9
13.2%
|
7
15.2%
|
7
17.9%
|
4
8.7%
|
6
9.4%
|
| Systemic AE Leading to Withdrawal |
1
1.5%
|
2
4.3%
|
0
0%
|
0
0%
|
2
3.1%
|
| AE with Fatal Outcome |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.6%
|
| Any Serious AE |
9
13.2%
|
11
23.9%
|
7
17.9%
|
5
10.9%
|
8
12.5%
|
| Any Related Serious AE |
0
0%
|
1
2.2%
|
0
0%
|
0
0%
|
0
0%
|
| Any Related AE |
3
4.4%
|
4
8.7%
|
3
7.7%
|
3
6.5%
|
0
0%
|
| Related Ocular AE in the Study Eye |
3
4.4%
|
4
8.7%
|
3
7.7%
|
3
6.5%
|
0
0%
|
| Related Systemic AE |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye by Highest Intensity, in All Participants |
|---|---|
| Description | The investigator assessed adverse event severity according to the following grading scale: Mild = Discomfort noticed, but no disruption of normal daily activity; Moderate = Discomfort sufficient to reduce or affect normal daily activity; Severe = Incapacitating with inability to work or to perform normal daily activity. Only the most severe intensity was counted for multiple occurrences of the same adverse event per participant at the preferred term level. Severity and seriousness are not synonymous; regardless of severity, some adverse events may have also met seriousness criteria. |
| Time Frame | From Baseline until 28 days after the last dose of study treatment (up to 36 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study treatment |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 67 | 46 | 39 | 46 | 64 |
| Study Eye - Adverse Event (AE) of Any Grade |
28
41.2%
|
21
45.7%
|
21
53.8%
|
27
58.7%
|
28
43.8%
|
| Study Eye - Mild AE |
27
39.7%
|
19
41.3%
|
20
51.3%
|
25
54.3%
|
24
37.5%
|
| Study Eye - Moderate AE |
4
5.9%
|
2
4.3%
|
3
7.7%
|
6
13%
|
8
12.5%
|
| Study Eye - Severe AE |
0
0%
|
3
6.5%
|
0
0%
|
0
0%
|
2
3.1%
|
| Fellow Eye - AE of Any Grade |
21
30.9%
|
16
34.8%
|
9
23.1%
|
18
39.1%
|
20
31.3%
|
| Fellow Eye - Mild AE |
15
22.1%
|
14
30.4%
|
7
17.9%
|
17
37%
|
17
26.6%
|
| Fellow Eye - Moderate AE |
5
7.4%
|
1
2.2%
|
4
10.3%
|
1
2.2%
|
2
3.1%
|
| Fellow Eye - Severe AE |
1
1.5%
|
1
2.2%
|
0
0%
|
0
0%
|
2
3.1%
|
| Title | Number of Participants With at Least One Systemic Adverse Event by Highest Intensity, in All Participants |
|---|---|
| Description | The investigator assessed adverse event severity according to the following grading scale: Mild = Discomfort noticed, but no disruption of normal daily activity; Moderate = Discomfort sufficient to reduce or affect normal daily activity; Severe = Incapacitating with inability to work or to perform normal daily activity. Only the most severe intensity was counted for multiple occurrences of the same adverse event per participant at the preferred term level. Severity and seriousness are not synonymous; regardless of severity, some adverse events may have also met seriousness criteria. |
| Time Frame | From Baseline until 28 days after the last dose of study treatment (up to 36 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study treatment |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 67 | 46 | 39 | 46 | 64 |
| Any Grade |
37
54.4%
|
37
80.4%
|
23
59%
|
30
65.2%
|
43
67.2%
|
| Mild |
30
44.1%
|
27
58.7%
|
17
43.6%
|
23
50%
|
28
43.8%
|
| Moderate |
16
23.5%
|
18
39.1%
|
14
35.9%
|
13
28.3%
|
26
40.6%
|
| Severe |
7
10.3%
|
2
4.3%
|
5
12.8%
|
4
8.7%
|
4
6.3%
|
| Title | Number of Participants With Abnormal Systolic Blood Pressure, in All Participants |
|---|---|
| Description | Abnormal systolic blood pressure (supine) was defined as any value outside of the standard reference range, from <70 (low) to >140 (high) millimetres of mercury (mmHg). Baseline was defined as the last non-missing predose assessment. Not every abnormal vital sign qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. |
| Time Frame | Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study treatment. In this analysis, the number of participants with an abnormal vital sign (numerator) is reported among the number analyzed (denominator), which represents the number of participants without the abnormal vital sign at baseline. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 67 | 46 | 39 | 46 | 64 |
| Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| High |
20
29.4%
|
13
28.3%
|
13
33.3%
|
23
50%
|
25
39.1%
|
| Title | Number of Participants With Abnormal Diastolic Blood Pressure, in All Participants |
|---|---|
| Description | Abnormal diastolic blood pressure (supine) was defined as any value outside of the standard reference range, from <40 (low) to >90 (high) millimetres of mercury (mmHg). Baseline was defined as the last non-missing predose assessment. Not every abnormal vital sign qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. |
| Time Frame | Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study treatment. In this analysis, the number of participants with an abnormal vital sign (numerator) is reported among the number analyzed (denominator), which represents the number of participants without the abnormal vital sign at baseline. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 67 | 46 | 39 | 46 | 64 |
| Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| High |
15
22.1%
|
9
19.6%
|
8
20.5%
|
10
21.7%
|
9
14.1%
|
| Title | Number of Participants With Abnormal Heart Rate, in All Participants |
|---|---|
| Description | Abnormal heart rate (supine) was defined as any value outside of the standard reference range, from <40 (low) to >100 (high) beats per minute. Baseline was defined as the last non-missing predose assessment. Not every abnormal vital sign qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. |
| Time Frame | Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study treatment. In this analysis, the number of participants with an abnormal vital sign (numerator) is reported among the number analyzed (denominator), which represents the number of participants without the abnormal vital sign at baseline. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 67 | 46 | 39 | 46 | 64 |
| Low |
1
1.5%
|
0
0%
|
1
2.6%
|
0
0%
|
0
0%
|
| High |
1
1.5%
|
0
0%
|
1
2.6%
|
1
2.2%
|
1
1.6%
|
| Title | Number of Participants With Abnormal Body Temperature, in All Participants |
|---|---|
| Description | Abnormal body temperature (supine) was defined as any value outside of the standard reference range, from <36.5 (low) to >37.5 (high) degrees Celsius. Baseline was defined as the last non-missing predose assessment. Not every abnormal vital sign qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. |
| Time Frame | Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study treatment. In this analysis, the number of participants with an abnormal vital sign (numerator) is reported among the number analyzed (denominator), which represents the number of participants without the abnormal vital sign at baseline. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 67 | 46 | 39 | 46 | 64 |
| Low |
28
41.2%
|
19
41.3%
|
14
35.9%
|
25
54.3%
|
29
45.3%
|
| High |
4
5.9%
|
1
2.2%
|
1
2.6%
|
2
4.3%
|
6
9.4%
|
| Title | Number of Participants With Marked Laboratory Abnormalities in Hematology and Coagulation Tests, in All Participants |
|---|---|
| Description | Clinical laboratory tests for hematology and coagulation parameters were performed and any marked abnormal values (High or Low) were based on Roche's predefined standard reference ranges. Marked laboratory abnormalities are presented according to COG3007 abnormality criteria: Single, Not Last = abnormality detected at a single assessment, but not at the last assessment; Last or Replicated = abnormality detected at the last assessment or replicated at one or more assessments. Not every laboratory abnormality qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. Abs. = absolute count; Corp. = corpuscular; Ery. = erythrocyte; INR = International Normalized Ratio |
| Time Frame | Predose at Baseline, Weeks 12 and 36, and at Early Termination and Unscheduled Visits (up to 36 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study treatment. This analysis included participants with non-missing assessments. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 67 | 46 | 39 | 46 | 64 |
| Basophils, Abs., High - Any Abnormality |
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Basophils, Abs., High - Single, Not Last |
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Basophils, Abs., High - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Eosinophils, Abs., High - Any Abnormality |
0
0%
|
0
0%
|
0
0%
|
3
6.5%
|
0
0%
|
| Eosinophils, Abs., High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
0
0%
|
| Eosinophils, Abs., High - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
2
4.3%
|
0
0%
|
| Ery. Mean Corp. Volume, Low - Any Abnormality |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
0
0%
|
| Ery. Mean Corp. Volume, Low - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
0
0%
|
| Ery. Mean Corp. Volume, Low - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Hematocrit, Low - Any Abnormality |
1
1.5%
|
0
0%
|
1
2.6%
|
0
0%
|
0
0%
|
| Hematocrit, Low - Single, Not Last |
1
1.5%
|
0
0%
|
1
2.6%
|
0
0%
|
0
0%
|
| Hematocrit, Low - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Hemoglobin, Low - Any Abnormality |
3
4.4%
|
0
0%
|
1
2.6%
|
2
4.3%
|
2
3.1%
|
| Hemoglobin, Low - Single, Not Last |
2
2.9%
|
0
0%
|
0
0%
|
0
0%
|
1
1.6%
|
| Hemoglobin, Low - Last or Replicated |
1
1.5%
|
0
0%
|
1
2.6%
|
2
4.3%
|
1
1.6%
|
| Lymphocytes, Abs., Low - Any Abnormality |
0
0%
|
1
2.2%
|
1
2.6%
|
2
4.3%
|
1
1.6%
|
| Lymphocytes, Abs., Low - Single, Not Last |
0
0%
|
1
2.2%
|
1
2.6%
|
0
0%
|
1
1.6%
|
| Lymphocytes, Abs., Low - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
2
4.3%
|
0
0%
|
| Lymphocytes, Abs., High - Any Abnormality |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
0
0%
|
| Lymphocytes, Abs., High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Lymphocytes, Abs., High - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
0
0%
|
| Lymphocytes, Pct., Low - Any Abnormality |
0
0%
|
1
2.2%
|
0
0%
|
0
0%
|
0
0%
|
| Lymphocytes, Pct., Low - Single, Not Last |
0
0%
|
1
2.2%
|
0
0%
|
0
0%
|
0
0%
|
| Lymphocytes, Pct., Low - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Neutrophils, Total, Abs., Low - Any Abnormality |
0
0%
|
1
2.2%
|
2
5.1%
|
3
6.5%
|
1
1.6%
|
| Neutrophils, Total, Abs., Low - Single, Not Last |
0
0%
|
1
2.2%
|
1
2.6%
|
1
2.2%
|
0
0%
|
| Neutrophils, Total, Abs., Low - Last or Replicated |
0
0%
|
0
0%
|
1
2.6%
|
2
4.3%
|
1
1.6%
|
| Neutrophils, Total, Abs., High - Any Abnormality |
2
2.9%
|
1
2.2%
|
0
0%
|
0
0%
|
2
3.1%
|
| Neutrophils, Total, Abs., High - Single, Not Last |
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
2
3.1%
|
| Neutrophils, Total, Abs., High -Last or Replicated |
1
1.5%
|
1
2.2%
|
0
0%
|
0
0%
|
0
0%
|
| Platelets, Low - Any Abnormality |
0
0%
|
0
0%
|
0
0%
|
2
4.3%
|
1
1.6%
|
| Platelets, Low - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
0
0%
|
| Platelets, Low - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
1
1.6%
|
| White Blood Cell Count, Low - Any Abnormality |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
1
1.6%
|
| White Blood Cell Count, Low - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
1
1.6%
|
| White Blood Cell Count, Low - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White Blood Cell Count, High - Any Abnormality |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
0
0%
|
| White Blood Cell Count, High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White Blood Cell Count, High - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
0
0%
|
| INR, High - Any Abnormality |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
0
0%
|
| INR, High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| INR, High - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
0
0%
|
| Title | Number of Participants With Marked Laboratory Abnormalities in Blood Chemistry Tests, in All Participants |
|---|---|
| Description | Clinical laboratory tests for blood chemistry parameters were performed and any marked abnormal values (High or Low) were based on Roche's predefined standard reference ranges. Marked laboratory abnormalities are presented according to COG3007 abnormality criteria: Single, Not Last = abnormality detected at a single assessment, but not at the last assessment; Last or Replicated = abnormality detected at the last assessment or replicated at one or more assessments. Not every laboratory abnormality qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. GGT = gamma-glutamyltransferase; SGOT/AST = serum glutamic oxaloacetic transaminase / aspartate aminotransferase; SGPT/ALT = serum glutamic pyruvic transaminase / alanine aminotransferase |
| Time Frame | Predose at Baseline, Weeks 12 and 36, and at Early Termination and Unscheduled Visits (up to 36 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study treatment. This analysis included participants with non-missing assessments. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 67 | 46 | 39 | 46 | 64 |
| Alkaline Phosphatase, High - Any Abnormality |
0
0%
|
0
0%
|
1
2.6%
|
0
0%
|
0
0%
|
| Alkaline Phosphatase, High - Single, Not Last |
0
0%
|
0
0%
|
1
2.6%
|
0
0%
|
0
0%
|
| Alkaline Phosphatase, High - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Bicarbonate (CO2), Low - Any Abnormality |
1
1.5%
|
1
2.2%
|
0
0%
|
1
2.2%
|
1
1.6%
|
| Bicarbonate (CO2), Low - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
0
0%
|
| Bicarbonate (CO2), Low - Last or Replicated |
1
1.5%
|
1
2.2%
|
0
0%
|
0
0%
|
1
1.6%
|
| Bicarbonate (CO2), High - Any Abnormality |
5
7.4%
|
3
6.5%
|
1
2.6%
|
3
6.5%
|
4
6.3%
|
| Bicarbonate (CO2), High - Single, Not Last |
3
4.4%
|
0
0%
|
1
2.6%
|
0
0%
|
2
3.1%
|
| Bicarbonate (CO2), High - Last or Replicated |
2
2.9%
|
3
6.5%
|
0
0%
|
3
6.5%
|
2
3.1%
|
| Calcium, Low - Any Abnormality |
0
0%
|
1
2.2%
|
0
0%
|
0
0%
|
0
0%
|
| Calcium, Low - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Calcium, Low - Last or Replicated |
0
0%
|
1
2.2%
|
0
0%
|
0
0%
|
0
0%
|
| Calcium, High - Any Abnormality |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.6%
|
| Calcium, High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.6%
|
| Calcium, High - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Chloride, Low - Any Abnormality |
1
1.5%
|
1
2.2%
|
0
0%
|
0
0%
|
2
3.1%
|
| Chloride, Low - Single, Not Last |
1
1.5%
|
1
2.2%
|
0
0%
|
0
0%
|
0
0%
|
| Chloride, Low - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
3.1%
|
| Creatine Kinase, High - Any Abnormality |
2
2.9%
|
0
0%
|
1
2.6%
|
3
6.5%
|
2
3.1%
|
| Creatine Kinase, High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
1
1.6%
|
| Creatine Kinase, High - Last or Replicated |
2
2.9%
|
0
0%
|
1
2.6%
|
2
4.3%
|
1
1.6%
|
| Creatinine, High - Any Abnormality |
0
0%
|
1
2.2%
|
0
0%
|
0
0%
|
0
0%
|
| Creatinine, High - Single, Not Last |
0
0%
|
1
2.2%
|
0
0%
|
0
0%
|
0
0%
|
| Creatinine, High - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| GGT, High - Any Abnormality |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
1
1.6%
|
| GGT, High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| GGT, High - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
1
1.6%
|
| Phosphorus, Low - Any Abnormality |
0
0%
|
1
2.2%
|
1
2.6%
|
0
0%
|
1
1.6%
|
| Phosphorus, Low - Single, Not Last |
0
0%
|
1
2.2%
|
0
0%
|
0
0%
|
0
0%
|
| Phosphorus, Low - Last or Replicated |
0
0%
|
0
0%
|
1
2.6%
|
0
0%
|
1
1.6%
|
| Phosphorus, High - Any Abnormality |
2
2.9%
|
3
6.5%
|
2
5.1%
|
1
2.2%
|
5
7.8%
|
| Phosphorus, High - Single, Not Last |
1
1.5%
|
1
2.2%
|
1
2.6%
|
1
2.2%
|
3
4.7%
|
| Phosphorus, High - Last or Replicated |
1
1.5%
|
2
4.3%
|
1
2.6%
|
0
0%
|
2
3.1%
|
| Potassium, High - Any Abnormality |
2
2.9%
|
1
2.2%
|
0
0%
|
0
0%
|
1
1.6%
|
| Potassium, High - Single, Not Last |
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Potassium, High - Last or Replicated |
1
1.5%
|
1
2.2%
|
0
0%
|
0
0%
|
1
1.6%
|
| Protein, Total, High - Any Abnormality |
0
0%
|
1
2.2%
|
0
0%
|
0
0%
|
0
0%
|
| Protein, Total, High - Single, Not Last |
0
0%
|
1
2.2%
|
0
0%
|
0
0%
|
0
0%
|
| Protein, Total, High - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| SGOT/AST, High - Any Abnormality |
0
0%
|
0
0%
|
1
2.6%
|
0
0%
|
1
1.6%
|
| SGOT/AST, High - Single, Not Last |
0
0%
|
0
0%
|
1
2.6%
|
0
0%
|
1
1.6%
|
| SGOT/AST, High - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| SGPT/ALT, High - Any Abnormality |
1
1.5%
|
0
0%
|
1
2.6%
|
0
0%
|
1
1.6%
|
| SGPT/ALT, High - Single, Not Last |
0
0%
|
0
0%
|
1
2.6%
|
0
0%
|
1
1.6%
|
| SGPT/ALT, High - Last or Replicated |
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Mean Change From Baseline in Intraocular Pressure in the Study Eye Over Time, in All Participants |
|---|---|
| Description | Intraocular pressure is the fluid pressure inside the eye. The method used to measure intraocular pressure (e.g., Goldmann tonometry) for each participant was to be applied consistently by the investigator throughout the study. On the day of dosing, intraocular pressure was monitored at 30 minutes post-treatment administration, and if intraocular pressure was ≥30 mmHg in the study eye, it was reassessed at 1 hour post-treatment administration. |
| Time Frame | Baseline, 0.5 hours postdose on Day 1, predose and 0.5 hours postdose at Weeks 4, 8, 12, 16, 20, 24, 28, and 32, and at Weeks 1, 13, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study treatment |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 67 | 46 | 39 | 46 | 64 |
| Baseline (BL): Absolute Value |
15.07
(3.38)
|
14.74
(3.08)
|
14.69
(3.85)
|
14.98
(2.91)
|
14.27
(2.80)
|
| Change from BL at Day 1 (0.5 hr) |
1.90
(4.80)
|
2.04
(5.32)
|
1.59
(4.30)
|
2.37
(4.22)
|
3.52
(4.79)
|
| Change from BL at Week 1 |
-0.89
(3.52)
|
-0.98
(3.47)
|
-0.62
(3.35)
|
-1.96
(2.98)
|
0.11
(2.36)
|
| Change from BL at Week 4 (Predose) |
-0.27
(3.16)
|
-1.40
(2.61)
|
-1.18
(3.85)
|
-0.87
(2.99)
|
0.59
(2.49)
|
| Change from BL at Week 4 (0.5 hr) |
2.88
(4.45)
|
2.70
(3.56)
|
2.05
(4.26)
|
1.51
(3.96)
|
3.59
(4.39)
|
| Change from BL at Week 8 (Predose) |
-0.56
(3.85)
|
-0.32
(3.13)
|
-0.69
(3.07)
|
-0.87
(2.75)
|
0.10
(2.64)
|
| Change from BL at Week 8 (0.5 hr) |
2.70
(4.21)
|
2.59
(4.64)
|
2.37
(5.15)
|
1.93
(3.91)
|
3.93
(4.52)
|
| Change from BL at Week 12 (Predose) |
-0.17
(3.49)
|
-0.02
(2.88)
|
-0.82
(3.37)
|
0.13
(2.94)
|
0.45
(2.45)
|
| Change from BL at Week 12 (0.5 hr) |
3.08
(4.01)
|
2.43
(3.41)
|
2.59
(3.95)
|
2.11
(4.04)
|
4.34
(5.25)
|
| Change from BL at Week 13 |
-0.77
(3.27)
|
-0.68
(3.12)
|
-0.71
(4.02)
|
-1.09
(2.70)
|
-0.65
(2.75)
|
| Change from BL at Week 16 (Predose) |
-0.41
(3.39)
|
0.02
(3.10)
|
-0.77
(3.11)
|
-1.00
(2.56)
|
-0.36
(2.83)
|
| Change from BL at Week 16 (0.5 hr) |
1.64
(4.62)
|
1.95
(5.35)
|
1.67
(3.92)
|
-0.30
(3.98)
|
3.12
(5.27)
|
| Change from BL at Week 20 (Predose) |
-0.16
(3.02)
|
-1.00
(2.73)
|
0.08
(3.61)
|
-0.44
(3.18)
|
-0.17
(2.71)
|
| Change from BL at Week 20 (0.5 hr) |
2.80
(4.81)
|
1.74
(4.85)
|
1.82
(5.37)
|
0.68
(5.45)
|
2.62
(4.54)
|
| Change from BL at Week 24 (Predose) |
0.00
(3.29)
|
-0.33
(3.30)
|
0.26
(2.77)
|
-0.61
(2.73)
|
0.14
(2.73)
|
| Change from BL at Week 24 (0.5 hr) |
3.23
(3.91)
|
3.26
(4.04)
|
4.11
(3.51)
|
0.91
(3.66)
|
4.17
(4.28)
|
| Change from BL at Week 28 (Predose) |
-0.02
(2.80)
|
0.00
(4.30)
|
-1.00
(2.91)
|
-0.38
(2.74)
|
-0.19
(2.89)
|
| Change from BL at Week 28 (0.5 hr) |
3.16
(4.28)
|
2.90
(4.13)
|
1.74
(4.80)
|
2.53
(3.60)
|
3.86
(4.49)
|
| Change from BL at Week 32 (Predose) |
-0.73
(3.72)
|
-0.23
(3.63)
|
-0.41
(3.07)
|
-0.80
(2.92)
|
-0.67
(3.06)
|
| Change from BL at Week 32 (0.5 hr) |
1.81
(5.10)
|
3.87
(5.58)
|
1.63
(5.47)
|
-0.98
(4.38)
|
2.37
(4.97)
|
| Change from BL at Week 36 |
0.00
(3.30)
|
0.25
(3.68)
|
-0.65
(3.85)
|
-0.20
(3.55)
|
-0.16
(3.18)
|
| Title | Change From Baseline in the Number of Participants With Anti-Drug Antibodies to Faricimab at Any Post-Baseline Timepoint |
|---|---|
| Description | Blood samples were obtained for measurement of anti-faricimab antibodies by a validated enzyme-linked immunosorbent assay (ELISA). |
| Time Frame | Baseline, Predose (0 hour) on Days 1, 28, 84, 112, 168, and 252 or early termination (up to 36 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study treatment. The analysis only included participants who received treatment with faricimab (i.e., Arm A was excluded) and had evaluable samples at baseline and any post-baseline timepoint. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 0 | 46 | 38 | 46 | 63 |
| ADA Negative to Missing |
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
|
| ADA Negative to ADA Negative |
41
60.3%
|
35
76.1%
|
36
92.3%
|
54
117.4%
|
|
| ADA Negative to ADA Positive |
3
4.4%
|
3
6.5%
|
9
23.1%
|
6
13%
|
|
| ADA Positive to Missing |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| ADA Positive to ADA Negative |
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
|
| ADA Positive to ADA Positive |
0
0%
|
0
0%
|
1
2.6%
|
3
6.5%
|
| Title | Mean Plasma Concentration of Faricimab Over Time, in All Participants |
|---|---|
| Description | Plasma concentrations of faricimab were measured by a specific validated enzyme-linked immunoabsorbent assay (ELISA) only from samples of participants randomized to receive faricimab. Baseline was defined as the last non-missing predose assessment. The lower limit of quantification (LLOQ) for the faricimab assay was 0.800 nanograms per millilitre (ng/mL). Values below the limit of quantification were imputed as LLOQ divided by 2. |
| Time Frame | Predose (on days when treatment was administered) at Baseline and Weeks 4, 12, 13, 16, 24, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis included all randomized participants who had received treatment with faricimab (i.e., excludes Arm A at all timepoints and Arm E at Week 4) and had evaluable pharmacokinetic samples at a given timepoint. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 0 | 46 | 39 | 46 | 64 |
| Baseline |
0.40
(0.00)
|
0.40
(0.00)
|
0.40
(0.00)
|
0.47
(0.59)
|
|
| Week 4 |
8.83
(5.85)
|
31.06
(18.47)
|
36.58
(19.78)
|
||
| Week 12 |
18.68
(24.38)
|
57.92
(57.65)
|
57.94
(73.91)
|
45.29
(105.64)
|
|
| Week 13 |
43.32
(31.98)
|
184.38
(102.01)
|
178.25
(119.98)
|
160.52
(124.73)
|
|
| Week 16 |
9.52
(7.41)
|
46.99
(35.19)
|
43.54
(39.05)
|
44.71
(50.55)
|
|
| Week 24 |
9.07
(7.39)
|
35.30
(22.03)
|
31.19
(24.13)
|
37.80
(27.75)
|
|
| Week 36 |
10.65
(8.47)
|
36.43
(30.80)
|
4.69
(7.24)
|
36.06
(26.93)
|
| Title | Mean Change From Baseline in Free Vascular Endothelial Growth Factor-A (VEGF-A) Plasma Concentrations Over Time, in All Participants |
|---|---|
| Description | The concentration of free VEGF was determined in plasma samples using an enzyme-linked immunosorbent assay (ELISA) method. The lower limit of quantification (LLOQ) of the assay was 15.6 picograms per millilitre (pg/mL). Plasma free VEGF concentrations below the limit of quantification were imputed as LLOQ divided by 2. |
| Time Frame | Baseline, Weeks 4, 12, 13, 16, 24, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis included all randomized participants who had received study treatment and had evaluable pharmacodynamic samples at a given timepoint. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 68 | 46 | 39 | 46 | 64 |
| Baseline (BL) - Value at Visit |
15.25
(10.60)
|
16.83
(12.08)
|
24.63
(31.47)
|
16.53
(9.73)
|
22.60
(27.79)
|
| Change from BL at Week 4 |
0.52
(12.20)
|
3.94
(33.25)
|
-9.26
(27.76)
|
-0.62
(15.67)
|
3.75
(53.99)
|
| Change from BL at Week 12 |
1.52
(19.45)
|
-0.46
(13.30)
|
-8.58
(20.73)
|
-4.70
(11.79)
|
-3.24
(27.79)
|
| Change from BL at Week 13 |
2.62
(21.69)
|
5.47
(52.19)
|
-14.10
(33.55)
|
-7.36
(10.67)
|
-15.14
(33.85)
|
| Change from BL at Week 16 |
12.12
(67.43)
|
-3.28
(10.61)
|
-9.86
(33.05)
|
-6.28
(10.84)
|
-5.34
(32.90)
|
| Change from BL at Week 24 |
-0.67
(10.45)
|
10.35
(50.09)
|
-12.57
(31.86)
|
-5.20
(10.07)
|
-7.19
(31.54)
|
| Change from BL at Week 36 |
1.91
(28.59)
|
-0.79
(11.86)
|
-12.16
(32.48)
|
-1.34
(13.69)
|
-8.17
(29.73)
|
| Title | Mean Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Concentrations Over Time, in All Participants |
|---|---|
| Description | Total Ang-2 concentrations were determined in plasma samples using an appropriate assay method. The lower limit of quantification (LLOQ) of the assay was 0.09 nanograms per millilitre (ng/mL). Plasma total Ang-2 concentrations below the limit of quantification were imputed as LLOQ divided by 2. |
| Time Frame | Baseline, Weeks 4, 12, 13, 16, 24, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis included all randomized participants who had received study treatment and had evaluable pharmacodynamic samples at a given timepoint. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 68 | 46 | 39 | 46 | 64 |
| Baseline (BL) - Value at Visit |
2.14
(1.38)
|
1.81
(0.67)
|
1.86
(1.12)
|
1.80
(0.71)
|
1.92
(0.95)
|
| Change from BL at Week 4 |
0.03
(0.48)
|
0.09
(0.39)
|
0.09
(0.27)
|
0.20
(0.49)
|
-0.03
(0.38)
|
| Change from BL at Week 12 |
0.10
(0.89)
|
0.14
(0.37)
|
0.22
(0.48)
|
0.19
(0.50)
|
-0.11
(0.49)
|
| Change from BL at Week 13 |
0.18
(0.91)
|
0.23
(0.35)
|
1.05
(1.15)
|
0.87
(0.76)
|
0.81
(0.98)
|
| Change from BL at Week 16 |
0.01
(0.62)
|
0.04
(0.71)
|
0.24
(0.47)
|
0.22
(0.61)
|
-0.01
(0.52)
|
| Change from BL at Week 24 |
0.00
(0.68)
|
0.11
(0.77)
|
0.21
(0.52)
|
0.24
(0.57)
|
0.04
(0.44)
|
| Change from BL at Week 36 |
0.08
(0.42)
|
0.05
(0.42)
|
0.25
(0.39)
|
0.33
(0.89)
|
0.05
(0.56)
|
| Title | Mean Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Concentrations Over Time, in All Participants |
|---|---|
| Description | Free Ang-2 concentrations were determined in plasma samples using an appropriate assay method. The lower limit of quantification (LLOQ) of the assay was 0.9 nanograms per millilitre (ng/mL). Plasma free Ang-2 concentrations below the limit of quantification were imputed as LLOQ divided by 2. |
| Time Frame | Baseline, Weeks 4, 12, 13, 16, 24, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis included all randomized participants who had received study treatment and had evaluable pharmacodynamic samples at a given timepoint. |
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. |
| Measure Participants | 68 | 46 | 39 | 46 | 64 |
| Baseline (BL) - Value at Visit |
2.19
(1.38)
|
1.81
(0.73)
|
1.88
(0.98)
|
1.73
(0.75)
|
1.95
(1.12)
|
| Change from BL at Week 4 |
0.00
(0.57)
|
0.14
(0.37)
|
-0.05
(0.46)
|
0.15
(0.62)
|
-0.07
(0.55)
|
| Change from BL at Week 12 |
0.23
(1.12)
|
0.20
(0.57)
|
0.12
(0.52)
|
0.21
(0.75)
|
-0.01
(0.59)
|
| Change from BL at Week 13 |
0.03
(0.92)
|
0.23
(0.69)
|
0.81
(1.11)
|
0.55
(0.75)
|
0.32
(0.93)
|
| Change from BL at Week 16 |
0.06
(0.77)
|
0.17
(0.95)
|
0.15
(0.62)
|
0.22
(0.67)
|
-0.11
(0.65)
|
| Change from BL at Week 24 |
0.18
(0.90)
|
0.20
(0.93)
|
0.25
(0.49)
|
0.39
(0.58)
|
0.13
(0.59)
|
| Change from BL at Week 36 |
0.16
(0.74)
|
0.25
(0.65)
|
0.28
(0.63)
|
0.51
(1.30)
|
0.06
(0.66)
|
Adverse Events
| Time Frame | From Baseline until 28 days after the last dose of study treatment (up to 36 weeks) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W | |||||
| Arm/Group Description | Participants received ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) once every 4 weeks (Q4W) up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit took place at Week 36. | Participants received faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit took place at Week 36. | Participants received faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit took place at Week 36. | Participants received ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit took place at Week 36. | |||||
All Cause Mortality |
||||||||||
| Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 1/64 (1.6%) | |||||
Serious Adverse Events |
||||||||||
| Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/67 (13.4%) | 11/46 (23.9%) | 7/39 (17.9%) | 5/46 (10.9%) | 8/64 (12.5%) | |||||
| Cardiac disorders | ||||||||||
| Acute myocardial infarction | 0/67 (0%) | 0/46 (0%) | 1/39 (2.6%) | 0/46 (0%) | 0/64 (0%) | |||||
| Atrial fibrillation | 0/67 (0%) | 0/46 (0%) | 1/39 (2.6%) | 1/46 (2.2%) | 0/64 (0%) | |||||
| Atrial flutter | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 1/46 (2.2%) | 0/64 (0%) | |||||
| Cardiac arrest | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Cardiac disorder | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Cardio-respiratory arrest | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Coronary artery disease | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Degenerative mitral valve disease | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Pericardial effusion | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Eye disorders | ||||||||||
| Glaucoma | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Keratic Precipitates | 0/67 (0%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Macular hole | 0/67 (0%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Neovascular age-related macular degeneration | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 1/46 (2.2%) | 0/64 (0%) | |||||
| Retinal haemorrhage | 0/67 (0%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Visual acuity reduced | 0/67 (0%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Constipation | 0/67 (0%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| General disorders | ||||||||||
| Chest pain | 0/67 (0%) | 0/46 (0%) | 1/39 (2.6%) | 0/46 (0%) | 0/64 (0%) | |||||
| Hepatobiliary disorders | ||||||||||
| Cholelithiasis | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Infections and infestations | ||||||||||
| Cystitis | 0/67 (0%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Endophthalmitis | 0/67 (0%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Escherichia urinary tract infection | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Herpes zoster | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 1/46 (2.2%) | 0/64 (0%) | |||||
| Infectious colitis | 0/67 (0%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Pneumonia | 0/67 (0%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Lower limb fracture | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 1/46 (2.2%) | 0/64 (0%) | |||||
| Road traffic accident | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Upper limb fracture | 0/67 (0%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Investigations | ||||||||||
| Arteriogram coronary | 0/67 (0%) | 0/46 (0%) | 1/39 (2.6%) | 0/46 (0%) | 0/64 (0%) | |||||
| Blood potassium increased | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Bladder cancer recurrent | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Invasive ductal breast carcinoma | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 1/46 (2.2%) | 0/64 (0%) | |||||
| Invasive lobular breast carcinoma | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Lung adenocarcinoma | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Pancreatic carcinoma | 0/67 (0%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Spindle cell sarcoma | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Squamous cell carcinoma | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Nervous system disorders | ||||||||||
| Cerebrovascular accident | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Transient ischaemic attack | 1/67 (1.5%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Nephrolithiasis | 0/67 (0%) | 0/46 (0%) | 1/39 (2.6%) | 0/46 (0%) | 0/64 (0%) | |||||
| Renal failure | 0/67 (0%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Postmenopausal haemorrhage | 0/67 (0%) | 0/46 (0%) | 1/39 (2.6%) | 0/46 (0%) | 0/64 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Pneumonia aspiration | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Surgical and medical procedures | ||||||||||
| Pulmonary resection | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Vascular disorders | ||||||||||
| Hypertension | 0/67 (0%) | 0/46 (0%) | 1/39 (2.6%) | 0/46 (0%) | 0/64 (0%) | |||||
| Shock | 0/67 (0%) | 0/46 (0%) | 1/39 (2.6%) | 0/46 (0%) | 0/64 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W) | Arm B: Faricimab, 1.5 mg Q4W | Arm C: Faricimab, 6 mg Q4W | Arm D: Faricimab, 6 mg Every 4-8 Weeks | Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 39/67 (58.2%) | 31/46 (67.4%) | 24/39 (61.5%) | 32/46 (69.6%) | 40/64 (62.5%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Vertigo | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 1/46 (2.2%) | 2/64 (3.1%) | |||||
| Eye disorders | ||||||||||
| Anterior chamber cell | 2/67 (3%) | 0/46 (0%) | 2/39 (5.1%) | 0/46 (0%) | 0/64 (0%) | |||||
| Blepharitis | 0/67 (0%) | 1/46 (2.2%) | 2/39 (5.1%) | 1/46 (2.2%) | 2/64 (3.1%) | |||||
| Cataract | 2/67 (3%) | 2/46 (4.3%) | 2/39 (5.1%) | 2/46 (4.3%) | 2/64 (3.1%) | |||||
| Conjunctival haemorrhage | 14/67 (20.9%) | 4/46 (8.7%) | 6/39 (15.4%) | 6/46 (13%) | 6/64 (9.4%) | |||||
| Dry age-related macular degeneration | 4/67 (6%) | 0/46 (0%) | 1/39 (2.6%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Eye irritation | 0/67 (0%) | 1/46 (2.2%) | 4/39 (10.3%) | 4/46 (8.7%) | 1/64 (1.6%) | |||||
| Eye pain | 2/67 (3%) | 4/46 (8.7%) | 2/39 (5.1%) | 5/46 (10.9%) | 3/64 (4.7%) | |||||
| Lacrimation increased | 1/67 (1.5%) | 0/46 (0%) | 1/39 (2.6%) | 3/46 (6.5%) | 0/64 (0%) | |||||
| Neovascular age-related macular degeneration | 6/67 (9%) | 4/46 (8.7%) | 3/39 (7.7%) | 2/46 (4.3%) | 5/64 (7.8%) | |||||
| Posterior capsule opacification | 2/67 (3%) | 1/46 (2.2%) | 3/39 (7.7%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Punctate keratitis | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 5/64 (7.8%) | |||||
| Retinal pigment epithelial tear | 3/67 (4.5%) | 0/46 (0%) | 2/39 (5.1%) | 2/46 (4.3%) | 0/64 (0%) | |||||
| Vision blurred | 2/67 (3%) | 1/46 (2.2%) | 3/39 (7.7%) | 2/46 (4.3%) | 2/64 (3.1%) | |||||
| Vitreous detachment | 3/67 (4.5%) | 5/46 (10.9%) | 3/39 (7.7%) | 5/46 (10.9%) | 4/64 (6.3%) | |||||
| Vitreous floaters | 2/67 (3%) | 3/46 (6.5%) | 4/39 (10.3%) | 3/46 (6.5%) | 1/64 (1.6%) | |||||
| Anterior chamber flare | 3/67 (4.5%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Dry eye | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 2/46 (4.3%) | 1/64 (1.6%) | |||||
| Visual acuity reduced | 1/67 (1.5%) | 1/46 (2.2%) | 0/39 (0%) | 2/46 (4.3%) | 0/64 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Constipation | 0/67 (0%) | 1/46 (2.2%) | 2/39 (5.1%) | 0/46 (0%) | 0/64 (0%) | |||||
| Diarrhoea | 1/67 (1.5%) | 2/46 (4.3%) | 1/39 (2.6%) | 2/46 (4.3%) | 1/64 (1.6%) | |||||
| General disorders | ||||||||||
| Pyrexia | 0/67 (0%) | 2/46 (4.3%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Sensation of foreign body | 0/67 (0%) | 1/46 (2.2%) | 0/39 (0%) | 2/46 (4.3%) | 0/64 (0%) | |||||
| Infections and infestations | ||||||||||
| Bronchitis | 0/67 (0%) | 2/46 (4.3%) | 2/39 (5.1%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Influenza | 3/67 (4.5%) | 3/46 (6.5%) | 1/39 (2.6%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Nasopharyngitis | 9/67 (13.4%) | 4/46 (8.7%) | 1/39 (2.6%) | 1/46 (2.2%) | 5/64 (7.8%) | |||||
| Pneumonia | 0/67 (0%) | 0/46 (0%) | 1/39 (2.6%) | 3/46 (6.5%) | 0/64 (0%) | |||||
| Urinary tract infection | 6/67 (9%) | 11/46 (23.9%) | 2/39 (5.1%) | 0/46 (0%) | 3/64 (4.7%) | |||||
| Cystitis | 1/67 (1.5%) | 1/46 (2.2%) | 0/39 (0%) | 0/46 (0%) | 3/64 (4.7%) | |||||
| Gastroenteritis viral | 3/67 (4.5%) | 0/46 (0%) | 0/39 (0%) | 1/46 (2.2%) | 0/64 (0%) | |||||
| Laryngitis | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 2/46 (4.3%) | 0/64 (0%) | |||||
| Sinusitis | 2/67 (3%) | 1/46 (2.2%) | 0/39 (0%) | 1/46 (2.2%) | 2/64 (3.1%) | |||||
| Tooth abscess | 1/67 (1.5%) | 2/46 (4.3%) | 1/39 (2.6%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Upper respiratory tract infection | 1/67 (1.5%) | 1/46 (2.2%) | 0/39 (0%) | 2/46 (4.3%) | 2/64 (3.1%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Fall | 2/67 (3%) | 2/46 (4.3%) | 1/39 (2.6%) | 3/46 (6.5%) | 3/64 (4.7%) | |||||
| Corneal abrasion | 0/67 (0%) | 0/46 (0%) | 1/39 (2.6%) | 0/46 (0%) | 2/64 (3.1%) | |||||
| Investigations | ||||||||||
| Intraocular pressure increased | 0/67 (0%) | 3/46 (6.5%) | 0/39 (0%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Weight decreased | 0/67 (0%) | 0/46 (0%) | 2/39 (5.1%) | 2/46 (4.3%) | 0/64 (0%) | |||||
| Weight increased | 0/67 (0%) | 0/46 (0%) | 2/39 (5.1%) | 0/46 (0%) | 1/64 (1.6%) | |||||
| Red blood cell sedimentation rate increased | 0/67 (0%) | 0/46 (0%) | 1/39 (2.6%) | 0/46 (0%) | 2/64 (3.1%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 0/67 (0%) | 2/46 (4.3%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Gout | 0/67 (0%) | 0/46 (0%) | 1/39 (2.6%) | 0/46 (0%) | 2/64 (3.1%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthritis | 0/67 (0%) | 0/46 (0%) | 1/39 (2.6%) | 0/46 (0%) | 2/64 (3.1%) | |||||
| Back pain | 1/67 (1.5%) | 2/46 (4.3%) | 1/39 (2.6%) | 0/46 (0%) | 3/64 (4.7%) | |||||
| Joint swelling | 0/67 (0%) | 2/46 (4.3%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Musculoskeletal pain | 0/67 (0%) | 0/46 (0%) | 1/39 (2.6%) | 1/46 (2.2%) | 2/64 (3.1%) | |||||
| Musculoskeletal stiffness | 0/67 (0%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 2/64 (3.1%) | |||||
| Pain in extremity | 2/67 (3%) | 0/46 (0%) | 0/39 (0%) | 2/46 (4.3%) | 1/64 (1.6%) | |||||
| Spinal osteoarthritis | 1/67 (1.5%) | 0/46 (0%) | 0/39 (0%) | 0/46 (0%) | 2/64 (3.1%) | |||||
| Nervous system disorders | ||||||||||
| Dizziness | 1/67 (1.5%) | 1/46 (2.2%) | 0/39 (0%) | 2/46 (4.3%) | 2/64 (3.1%) | |||||
| Headache | 0/67 (0%) | 2/46 (4.3%) | 0/39 (0%) | 2/46 (4.3%) | 2/64 (3.1%) | |||||
| Migraine | 0/67 (0%) | 2/46 (4.3%) | 0/39 (0%) | 0/46 (0%) | 0/64 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Anxiety | 2/67 (3%) | 1/46 (2.2%) | 1/39 (2.6%) | 1/46 (2.2%) | 4/64 (6.3%) | |||||
| Insomnia | 1/67 (1.5%) | 0/46 (0%) | 2/39 (5.1%) | 0/46 (0%) | 0/64 (0%) | |||||
| Depression | 0/67 (0%) | 2/46 (4.3%) | 0/39 (0%) | 1/46 (2.2%) | 0/64 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Sinus congestion | 2/67 (3%) | 1/46 (2.2%) | 0/39 (0%) | 2/46 (4.3%) | 2/64 (3.1%) | |||||
| Vascular disorders | ||||||||||
| Hypertension | 2/67 (3%) | 1/46 (2.2%) | 1/39 (2.6%) | 3/46 (6.5%) | 3/64 (4.7%) | |||||
Limitations/Caveats
The small number of participants per cohort only allows detection of large differences in outcomes; not designed to show noninferiority of faricimab relative to ranibizumab. The short duration further limits information on long-term visual potential.
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 |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02484690
Other Study ID Numbers:
- BP29647
First Posted:
Jun 30, 2015
Last Update Posted:
Nov 12, 2020
Last Verified:
Oct 1, 2020