BOULEVARD: A Study of Faricimab (RO6867461) in Participants With Center-Involving Diabetic Macular Edema
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02699450
Collaborator
(none)
229
60
3
19.6
3.8
0.2
Study Details
Study Description
Brief Summary
This is a multiple-center, multiple-dose, randomized, active comparator-controlled, double-masked, three parallel group, 36-week study in participants with center-involving diabetic macular edema (DME). Only one eye will be selected as the study eye. Where both eyes meet all eligibility criteria, the eye with the worse best corrected visual acuity (BCVA) will be defined as the study eye. The study will consist of a treatment period (20 weeks) and an observational period (up to 16 weeks). Treatment naive participants will be randomized in a 1:1:1 ratio to one of the Arms A, B and C, respectively. Participants previously treated with intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) will be randomized in a 1:1 ratio to Arms A and C.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
229 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Multiple-Center, Multiple-Dose, 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 Diabetic Macular Edema
Actual Study Start Date
:
Apr 27, 2016
Actual Primary Completion Date
:
Sep 15, 2017
Actual Study Completion Date
:
Dec 14, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Arm A: 0.3 mg Ranibizumab Participants will receive 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant meets pre-specified criteria the participant will receive a single dose of 0.3 mg ranibizumab and exit the study. |
Drug: Ranibizumab
Ranibizumab will be administered by IVT injection in the study eye.
Other Names:
|
| Experimental: Arm B: 1.5 mg Faricimab Participants will receive 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant meets pre-specified criteria the participant will receive a single dose of 0.3 mg ranibizumab and exit the study. |
Drug: Faricimab
Faricimab will be administered by IVT injection in the study eye.
Other Names:
|
| Experimental: Arm C: 6 mg Faricimab Participants will receive 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant meets pre-specified criteria the participant will receive a single dose of 0.3 mg ranibizumab and exit the study. |
Drug: Faricimab
Faricimab will be administered by IVT injection in the study eye.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Mean Change From Baseline in BCVA Letter Score at Week 24, in Treatment-Naive Participants [Baseline, Week 24]
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 primary analysis used a Linear Mixed Effects Model for Repeated Measurements. Missing values were not imputed; it was assumed that the data were missing at random.
Secondary Outcome Measures
- Mean Change From Baseline in BCVA Letter Score at Week 24, in Previously Treated Participants [Baseline, Week 24]
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 primary analysis used a Linear Mixed Effects Model for Repeated Measurements. Missing values were not imputed; it was assumed that the data were missing at random.
- Mean Change From Baseline in BCVA Letter Score at Week 24, in All Participants [Baseline, Week 24]
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 primary analysis used a Linear Mixed Effects Model for Repeated Measurements. Missing values were not imputed; it was assumed that the data were missing at random.
- Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in Treatment-Naive Participants [Baseline, Week 24]
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.
- Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in Previously Treated Participants [Baseline up to Week 24]
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.
- Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in All Participants [Baseline up to Week 24]
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.
- Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in Treatment-Naive Participants [Week 24]
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.
- Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in Previously Treated Participants [Week 24]
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.
- Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in All Participants [Week 24]
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.
- Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in Treatment-Naive Participants [Week 24]
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.
- Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in Previously Treated Participants [Week 24]
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.
- Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in All Participants [Week 24]
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.
- Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in Treatment-Naive Participants [Baseline, Week 24]
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).
- Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in Previously Treated Participants [Baseline, Week 24]
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).
- Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in All Participants [Baseline, Week 24]
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).
- Mean Change From Baseline in Central Subfield Thickness at Week 24, in Treatment-Naive Participants [Baseline, Week 24]
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 SD-OCT.
- Mean Change From Baseline in Central Subfield Thickness at Week 24, in Previously Treated Participants [Baseline, Week 24]
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 SD-OCT.
- Mean Change From Baseline in Central Subfield Thickness at Week 24, in All Participants [Baseline, Week 24]
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 SD-OCT.
- Percentage of Participants With Presence of Subretinal Fluid in the Study Eye at Week 24, in Treatment-Naive Participants [Week 24]
Subretinal fluid is defined as the presence of fluid between the retina and the retinal pigment epithelium. Resolution of subretinal fluid was measured using SD-OCT.
- Percentage of Participants With Presence of Subretinal Fluid in the Study Eye at Week 24, in Previously Treated Participants [Week 24]
Subretinal fluid is defined as the presence of fluid between the retina and the retinal pigment epithelium. Resolution of subretinal fluid was measured using SD-OCT.
- Percentage of Participants With Presence of Intraretinal Fluid in the Study Eye at Week 24, in Treatment-Naive Participants [Week 24]
Intraretinal fluid is described as the presence of fluid within the retina. Resolution of intraretinal fluid was measured by SD-OCT.
- Percentage of Participants With Presence of Intraretinal Fluid in the Study Eye at Week 24, in Previously Treated Participants [Week 24]
Intraretinal fluid is described as the presence of fluid within the retina. Resolution of intraretinal fluid was measured by SD-OCT.
- Number of Participants With Presence or Absence of Leakage at the Macula at Week 24, in Treatment-Naive Participants [Week 24]
Leakage at the macula describes the leakage of fluorescein at the macula region as measured by fundus fluorescein angiography (FFA).
- Number of Participants With Presence or Absence of Leakage at the Macula at Week 24, in Previously Treated Participants [Week 24]
Leakage at the macula describes the leakage of fluorescein at the macula region as measured by fundus fluorescein angiography (FFA).
- Mean Change From Baseline in the Size of the Foveal Avascular Zone at Week 24, in All Participants [Baseline, Week 24]
The size of the foveal avascular zone was to be measured by fundus fluorescein angiography (FFA).
- Mean Plasma Concentrations of Ranibizumab (Arm A) or Faricimab (Arms B and C) Over Time, in All Participants [Predose at Baseline and Weeks 1, 4, 12, 20, 24, 26, 28, 32, and 36]
Plasma concentrations of ranibizumab were measured by an appropriate assay only from samples of participants randomized to Arm A: 0.3 mg Ranibizumab. Plasma concentrations of faricimab were measured by a specific validated enzyme-linked immunoabsorbent assay (ELISA) only from samples of participants randomized to Arm B: 1.5 mg Faricimab and Arm C: 6 mg Faricimab. Baseline was defined as the last non-missing predose assessment. The lower limit of quantification (LLOQ) for the ranibizumab and faricimab assays were 0.015 nanograms per millilitre (ng/mL) and 0.800 ng/mL, respectively. Values below the limit of quantification were imputed as LLOQ divided by 2.
- Baseline and Change From Baseline in Free Vascular Endothelial Growth Factor (VEGF) Plasma Levels Over Time, in Treatment-Naive Participants [Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, 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.
- Baseline and Change From Baseline in Free Vascular Endothelial Growth Factor (VEGF) Plasma Levels Over Time, in Previously Treated Participants [Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, 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.
- Baseline and Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Treatment-Naive Participants [Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, 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.
- Baseline and Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Treatment-Naive Participants [Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, 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.
- Baseline and Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Previously Treated Participants [Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, 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.
- Baseline and Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Previously Treated Participants [Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, 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.
- Safety Summary of the Number of Participants With at Least One Adverse Event During the Treatment Period (up to Week 24), in All Participants [From Baseline up to Week 24]
This safety summary reports the number and percentage of participants who experienced at least one adverse event (AE) within 28 days of the end of the treatment period (i.e., up to Week 24). 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 of treatment with study drug, and AEs with fatal outcome. Multiple occurrences of the same AE in one individual were counted only once.
- Safety Summary of the Number of Participants With at Least One Adverse Event During the Post-Treatment Observation Period, in All Participants [From Week 24 up to Week 36]
This safety summary reports the number and percentage of participants who experienced at least one adverse event (AE) during the post-treatment observation period (i.e., from Week 24 up to Week 36). 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 of treatment with study drug, and AEs with fatal outcome. Multiple occurrences of the same AE in one individual were counted only once.
- Number of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye During the Treatment Period by Highest Intensity, in All Participants [From Baseline up to Week 24]
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 During the Treatment Period by Highest Intensity, in All Participants [From Baseline up to Week 24]
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 Over Time, in All Participants [Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36]
Abnormal systolic blood pressure (supine) was defined as any value outside of the standard reference range, from <70 (low) to >180 (high) millimetres of mercury (mmHg) or a change from baseline of greater than 30 mmHg (decrease or increase). 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 Over Time, in All Participants [Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36]
Abnormal diastolic blood pressure (supine) was defined as any value outside of the standard reference range, from <40 (low) to >110 (high) millimetres of mercury (mmHg) or a change from baseline of greater than 20 mmHg (decrease or increase). 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 an Abnormal Heart Rate Over Time, in All Participants [Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36]
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 Over Time, in All Participants [Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36]
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.
- Mean Heart Rate at Baseline and Week 24, as Measured by Electrocardiogram in All Participants [Baseline, Week 24]
Triplicate 12-lead electrocardiogram (ECG), i.e., three useful ECGs without artifacts, were performed on all evaluable participants. To minimize variability, it was important that participants be in a resting position for at least 10 minutes prior to the ECG evaluation. Body position was to be consistently maintained for each ECG evaluation to prevent changes in heart rate. Environmental distractions (e.g., television, radio, conversation, mobile phones) were to be minimized before and during ECG recording. Triplicate ECGs were to be obtained within a 5-minute interval. The predefined standard reference range for heart rate measured by ECG was 40 (low) to 100 (high) beats per minute.
- Mean PR, RR, QT, QRS, QTcB, and QTcF Intervals at Baseline and Week 24, as Measured by Electrocardiogram in All Participants [Baseline, Week 24]
Triplicate 12-lead electrocardiogram (ECG), i.e., three useful ECGs without artifacts, were performed on all evaluable participants. To minimize variability, it was important that participants be in a resting position for at least 10 minutes prior to the ECG evaluation. Body position was to be consistently maintained for each ECG evaluation to prevent changes in heart rate. Environmental distractions (e.g., television, radio, conversation, mobile phones) were to be minimized before and during ECG recording. Triplicate ECGs were to be obtained within a 5-minute interval. Baseline was defined as the last non-missing predose assessment. The predefined standard reference ranges for the intervals measured by ECG were defined as follows (ranges are from low to high, in milliseconds [msec]): PR: 120-200 msec; RR: 600-1500 msec; QT: 200-500 msec; QRS: 40-120 msec.
- Number of Participants With Marked Laboratory Abnormalities in Hematology Tests, in All Participants [Predose at Baseline, Weeks 12 and 24, and at Early Termination and Unscheduled Visits (up to 36 weeks)]
Clinical laboratory tests for hematology 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; Ery. = erythrocyte; Hemo. = hemoglobin
- Number of Participants With Marked Laboratory Abnormalities in Blood Chemistry Tests, in All Participants [Predose at Baseline, Weeks 12 and 24, 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. SGOT/AST = serum glutamic oxaloacetic transaminase / aspartate aminotransferase
- Number of Participants With Marked Laboratory Abnormalities in Coagulation Tests, in All Participants [Predose at Baseline, Weeks 12 and 24, and at Early Termination and Unscheduled Visits (up to 36 weeks)]
Clinical laboratory tests for 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. aPTT = activated partial thromboplastin time; INR = International Normalized Ratio (prothrombin time)
- Number of Participants Who Tested Negative or Positive for Anti-Drug Antibodies Against Faricimab Over Time [Baseline and Weeks 1, 4, 12, 16, 20, 24, 26, 28, 32, and 36]
The number and percentage of participants who tested negative or positive for plasma anti-drug antibodies (ADA) to faricimab at baseline and at the study visits was tabulated, except for those who were randomized to treatment with ranibizumab in Arm A.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Macular edema associated with diabetic retinopathy
-
Decreased visual acuity attributable primarily to DME
-
Diagnosis of diabetes mellitus
Exclusion Criteria:
-
High risk proliferative diabetic retinopathy
-
Cataract surgery within 3 months of Baseline, or any other previous intraocular surgery
-
Uncontrolled glaucoma
-
Current or history of ocular disease in the study eye other than DME
-
Major illness or major surgical procedure within 1 month prior to Day 1
-
Uncontrolled blood pressure
-
Glycosylated hemoglobin (HbA1c) greater than (>) 12 percent (%) at screening
-
Untreated diabetes mellitus or initiation of oral anti-diabetic medication or insulin within 4 months prior to Day 1
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Retinal Research Institute, LLC | Phoenix | Arizona | United States | 85014 |
| 2 | Associated Retina Consultants | Phoenix | Arizona | United States | 85020 |
| 3 | Arizona Retina and Vitreous Consultants | Phoenix | Arizona | United States | 85021 |
| 4 | Retina Associates Southwest PC | Tucson | Arizona | United States | 85750 |
| 5 | Retina Consultants of Orange County | Fullerton | California | United States | 92835 |
| 6 | United Med Res Inst | Inglewood | California | United States | 90301 |
| 7 | Northern California Retina Vitreous Associates | Mountain View | California | United States | 94040 |
| 8 | Ophthalmic Clinical Trials San Diego | Oceanside | California | United States | 92056 |
| 9 | Southern CA Desert Retina Cons | Palm Desert | California | United States | 92211 |
| 10 | Retina Consultants, San Diego | Poway | California | United States | 92064 |
| 11 | Retinal Consultants Med Group | Sacramento | California | United States | 95825 |
| 12 | California Retina Consultants | Santa Barbara | California | United States | 93103 |
| 13 | Bay Area Retina Associates | Walnut Creek | California | United States | 94598 |
| 14 | Retina Consultants of Southern | Colorado Springs | Colorado | United States | 80909 |
| 15 | Rand Eye | Deerfield Beach | Florida | United States | 33064 |
| 16 | National Ophthalmic Research Institute | Fort Myers | Florida | United States | 33912 |
| 17 | Florida Eye Associates | Melbourne | Florida | United States | 32901 |
| 18 | Retina Specialty Institute | Pensacola | Florida | United States | 32503 |
| 19 | Retina Vitreous Assoc of FL | Saint Petersburg | Florida | United States | 33711 |
| 20 | Southern Vitreoretinal Assoc | Tallahassee | Florida | United States | 32308 |
| 21 | Southeast Retina Center | Augusta | Georgia | United States | 30909 |
| 22 | Georgia Retina PC | Marietta | Georgia | United States | 30060 |
| 23 | Univ of Illinois at Chicago | Chicago | Illinois | United States | 60612 |
| 24 | University Retina and Macula Associates, PC | Oak Forest | Illinois | United States | 60452 |
| 25 | Illinois Retina Associates SC | Oak Park | Illinois | United States | 60304 |
| 26 | Midwest Eye Institute | Indianapolis | Indiana | United States | 46290 |
| 27 | Wolfe Eye Clinic | West Des Moines | Iowa | United States | 50266 |
| 28 | Retina Associates of Kentucky | Lexington | Kentucky | United States | 40509 |
| 29 | Paducah Retinal Center | Paducah | Kentucky | United States | 42001 |
| 30 | Wilmer Eye Institute | Baltimore | Maryland | United States | 21287 |
| 31 | Vitreo-Retinal Associates | Grand Rapids | Michigan | United States | 49546 |
| 32 | Vitreoretinal Surgery | Edina | Minnesota | United States | 55435 |
| 33 | Sierra Eye Associates | Reno | Nevada | United States | 89502 |
| 34 | Retina Center of New Jersey | Bloomfield | New Jersey | United States | 07003 |
| 35 | Eye Associates of New Mexico | Albuquerque | New Mexico | United States | 87102 |
| 36 | University of New Mexico | Albuquerque | New Mexico | United States | 87131 |
| 37 | Capital Region Retina | Albany | New York | United States | 12206 |
| 38 | Opthalmic Consultants of LI | Lynbrook | New York | United States | 11563 |
| 39 | Retina Consultants of Western New York | Orchard Park | New York | United States | 14127 |
| 40 | Western Carolina Retinal Associate PA | Asheville | North Carolina | United States | 28803 |
| 41 | Char Eye Ear &Throat Assoc | Charlotte | North Carolina | United States | 28210 |
| 42 | Cleveland Clinic Foundation; Cole Eye Institute | Cleveland | Ohio | United States | 44195 |
| 43 | OSU Eye Physicians & Surgeons | Columbus | Ohio | United States | 43212 |
| 44 | Oregon Retina, LLP | Eugene | Oregon | United States | 97401 |
| 45 | Retina Northwest | Portland | Oregon | United States | 97221 |
| 46 | Palmetto Retina Center | Florence | South Carolina | United States | 29501 |
| 47 | Charleston Neuroscience Inst | Ladson | South Carolina | United States | 29456 |
| 48 | Charles Retina Institute | Germantown | Tennessee | United States | 38138 |
| 49 | Tennessee Retina PC. | Nashville | Tennessee | United States | 37203 |
| 50 | W Texas Retina Consultants PA | Abilene | Texas | United States | 79606 |
| 51 | Austin Retina Associates | Austin | Texas | United States | 78705 |
| 52 | Retina Consultants of Austin | Austin | Texas | United States | 78705 |
| 53 | Retina Specialists | DeSoto | Texas | United States | 75115 |
| 54 | Retina Consultants of Houston | Houston | Texas | United States | 77030 |
| 55 | Med Center Ophthalmology Assoc | San Antonio | Texas | United States | 78240 |
| 56 | Retina Consultants of Houston | The Woodlands | Texas | United States | 77384 |
| 57 | Retina Associates of Utah | Salt Lake City | Utah | United States | 84107 |
| 58 | Univ of Virginia Ophthalmology | Charlottesville | Virginia | United States | 22903 |
| 59 | Spokane Eye Clinical Research | Spokane | Washington | United States | 99204 |
| 60 | West Virginia University Eye Institute | Morgantown | West Virginia | United States | 26506 |
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:
NCT02699450
Other Study ID Numbers:
- BP30099
- RG7716
First Posted:
Mar 4, 2016
Last Update Posted:
Sep 25, 2020
Last Verified:
Aug 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 229 patients were randomized, but two participants randomized to Arm C: 6 mg Faricimab were excluded from the analysis populations due to Good Clinical Practice (GCP) non-compliance at a single site. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Period Title: Overall Study | |||
| STARTED | 90 | 55 | 82 |
| Received at Least One Dose of Study Drug | 89 | 55 | 80 |
| Completed up to Week 24 | 81 | 53 | 73 |
| COMPLETED | 75 | 50 | 67 |
| NOT COMPLETED | 15 | 5 | 15 |
Baseline Characteristics
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Total of all reporting groups |
| Overall Participants | 90 | 55 | 82 | 227 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| All Participants |
62.3
(9.2)
|
61.5
(7.7)
|
60.8
(9.2)
|
61.6
(8.8)
|
| Treatment-Naive Participants |
61.6
(9.5)
|
61.4
(7.7)
|
60.5
(9.1)
|
61.2
(8.8)
|
| Previously Treated Participants |
63.5
(8.7)
|
63.0
(NA)
|
61.5
(9.5)
|
62.6
(9.0)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
36
40%
|
35
63.6%
|
36
43.9%
|
107
47.1%
|
| Male |
54
60%
|
20
36.4%
|
46
56.1%
|
120
52.9%
|
| Female |
22
24.4%
|
35
63.6%
|
20
24.4%
|
77
33.9%
|
| Male |
37
41.1%
|
19
34.5%
|
33
40.2%
|
89
39.2%
|
| Female |
14
15.6%
|
0
0%
|
16
19.5%
|
30
13.2%
|
| Male |
17
18.9%
|
1
1.8%
|
13
15.9%
|
31
13.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
15
16.7%
|
8
14.5%
|
16
19.5%
|
39
17.2%
|
| Not Hispanic or Latino |
74
82.2%
|
47
85.5%
|
66
80.5%
|
187
82.4%
|
| Unknown or Not Reported |
1
1.1%
|
0
0%
|
0
0%
|
1
0.4%
|
| Hispanic or Latino |
11
12.2%
|
8
14.5%
|
9
11%
|
28
12.3%
|
| Not Hispanic or Latino |
48
53.3%
|
46
83.6%
|
44
53.7%
|
138
60.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Hispanic or Latino |
4
4.4%
|
0
0%
|
7
8.5%
|
11
4.8%
|
| Not Hispanic or Latino |
26
28.9%
|
1
1.8%
|
22
26.8%
|
49
21.6%
|
| Unknown or Not Reported |
1
1.1%
|
0
0%
|
0
0%
|
1
0.4%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
1
1.1%
|
0
0%
|
2
2.4%
|
3
1.3%
|
| Asian |
0
0%
|
0
0%
|
1
1.2%
|
1
0.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
17
18.9%
|
11
20%
|
14
17.1%
|
42
18.5%
|
| White |
71
78.9%
|
43
78.2%
|
61
74.4%
|
175
77.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
1.1%
|
1
1.8%
|
4
4.9%
|
6
2.6%
|
| American Indian or Alaska Native |
0
0%
|
0
0%
|
2
2.4%
|
2
0.9%
|
| Asian |
0
0%
|
0
0%
|
1
1.2%
|
1
0.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
9
10%
|
11
20%
|
10
12.2%
|
30
13.2%
|
| White |
49
54.4%
|
42
76.4%
|
39
47.6%
|
130
57.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
1.1%
|
1
1.8%
|
1
1.2%
|
3
1.3%
|
| American Indian or Alaska Native |
1
1.1%
|
0
0%
|
0
0%
|
1
0.4%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
8
8.9%
|
0
0%
|
4
4.9%
|
12
5.3%
|
| White |
22
24.4%
|
1
1.8%
|
22
26.8%
|
45
19.8%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
3
3.7%
|
3
1.3%
|
| Anti-VEGF Treatment Experience Status (Treatment-Naive or Previously Treated) (Count of Participants) | ||||
| Treatment-Naive |
59
65.6%
|
54
98.2%
|
53
64.6%
|
166
73.1%
|
| Previously Treated |
31
34.4%
|
1
1.8%
|
29
35.4%
|
61
26.9%
|
| Best Corrected Visual Acuity (BCVA) ETDRS Letter Score in the Study Eye at Baseline (Score on a scale) [Mean (Standard Deviation) ] | ||||
| All Participants |
61.51
(10.43)
|
61.16
(11.12)
|
59.48
(12.49)
|
60.70
(11.36)
|
| Treatment-Naive Participants |
61.24
(9.87)
|
60.94
(11.11)
|
60.00
(10.95)
|
60.75
(10.58)
|
| Previously Treated Participants |
62.00
(11.56)
|
73.00
(NA)
|
58.55
(14.98)
|
60.54
(13.31)
|
| Previous Macular Laser Treatment Status (Count of Participants) | ||||
| Previous Macular Laser Treatment |
16
17.8%
|
4
7.3%
|
15
18.3%
|
35
15.4%
|
| No Previous Macular Laser Treatment |
74
82.2%
|
51
92.7%
|
67
81.7%
|
192
84.6%
|
| Previous Macular Laser Treatment |
6
6.7%
|
4
7.3%
|
3
3.7%
|
13
5.7%
|
| No Previous Macular Laser Treatment |
53
58.9%
|
50
90.9%
|
50
61%
|
153
67.4%
|
| Previous Macular Laser Treatment |
10
11.1%
|
0
0%
|
12
14.6%
|
22
9.7%
|
| No Previous Macular Laser Treatment |
21
23.3%
|
1
1.8%
|
17
20.7%
|
39
17.2%
|
| Mean Foveal Center Point Thickness at Baseline (micrometers) [Mean (Standard Deviation) ] | ||||
| All Participants |
459.88
(162.09)
|
494.64
(200.51)
|
440.50
(150.42)
|
461.49
(168.97)
|
| Treatment-Naive Participants |
464.19
(166.00)
|
497.78
(201.02)
|
456.70
(156.12)
|
472.97
(175.37)
|
| Previously Treated Participants |
451.82
(156.87)
|
325.00
(NA)
|
412.02
(137.83)
|
430.82
(147.49)
|
| Mean Central Subfield Thickness at Baseline (micrometers) [Mean (Standard Deviation) ] | ||||
| All Participants |
489.01
(136.74)
|
532.89
(162.72)
|
485.31
(130.10)
|
498.46
(142.04)
|
| Treatment-Naive Participants |
490.88
(139.01)
|
535.44
(163.13)
|
496.47
(134.96)
|
507.39
(146.71)
|
| Previously Treated Participants |
485.52
(134.56)
|
395.00
(NA)
|
465.69
(120.86)
|
474.61
(126.79)
|
| Number of Participants with Absence/Presence of Subretinal Fluid in the Study Eye at Baseline (Count of Participants) | ||||
| Subretinal Fluid Absent |
49
54.4%
|
30
54.5%
|
44
53.7%
|
123
54.2%
|
| Subretinal Fluid Present |
40
44.4%
|
25
45.5%
|
36
43.9%
|
101
44.5%
|
| Subretinal Fluid Absent |
34
37.8%
|
30
54.5%
|
25
30.5%
|
89
39.2%
|
| Subretinal Fluid Present |
24
26.7%
|
24
43.6%
|
26
31.7%
|
74
32.6%
|
| Subretinal Fluid Absent |
15
16.7%
|
0
0%
|
19
23.2%
|
34
15%
|
| Subretinal Fluid Present |
16
17.8%
|
1
1.8%
|
10
12.2%
|
27
11.9%
|
| Number of Participants with Absence/Presence of Intraretinal Fluid at Baseline (Count of Participants) | ||||
| Intraretinal Fluid Absent |
1
1.1%
|
0
0%
|
0
0%
|
1
0.4%
|
| Intraretinal Fluid Present |
87
96.7%
|
55
100%
|
78
95.1%
|
220
96.9%
|
| Intraretinal Fluid Absent |
1
1.1%
|
0
0%
|
0
0%
|
1
0.4%
|
| Intraretinal Fluid Present |
57
63.3%
|
54
98.2%
|
49
59.8%
|
160
70.5%
|
| Intraretinal Fluid Absent |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Intraretinal Fluid Present |
30
33.3%
|
1
1.8%
|
29
35.4%
|
60
26.4%
|
Outcome Measures
| Title | Mean Change From Baseline in BCVA Letter Score at Week 24, 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 primary analysis used a Linear Mixed Effects Model for Repeated Measurements. Missing values were not imputed; it was assumed that the data were missing at random. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 49 | 49 | 44 |
| Least Squares Mean (80% Confidence Interval) [BCVA letters] |
10.3
|
11.7
|
13.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.37 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline BCVA. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 1.4 | |
| Confidence Interval |
(2-Sided) 80% -0.6 to 3.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.03 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline BCVA. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 3.6 | |
| Confidence Interval |
(2-Sided) 80% 1.5 to 5.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Change From Baseline in BCVA Letter Score at Week 24, in Previously Treated 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 primary analysis used a Linear Mixed Effects Model for Repeated Measurements. Missing values were not imputed; it was assumed that the data were missing at random. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm C: 6 mg Faricimab |
|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 28 | 23 |
| Least Squares Mean (80% Confidence Interval) [BCVA letters] |
8.9
|
9.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.63 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline BCVA. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 1.3 | |
| Confidence Interval |
(2-Sided) 80% -2.3 to 5.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Change From Baseline in BCVA Letter Score at Week 24, in All 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 primary analysis used a Linear Mixed Effects Model for Repeated Measurements. Missing values were not imputed; it was assumed that the data were missing at random. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 77 | 50 | 67 |
| Least Squares Mean (80% Confidence Interval) [BCVA letters] |
9.4
|
11.7
|
12.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.15 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline BCVA. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 2.3 | |
| Confidence Interval |
(2-Sided) 80% 0.2 to 4.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.04 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline BCVA. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 2.9 | |
| Confidence Interval |
(2-Sided) 80% 1.1 to 4.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, 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 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 49 | 49 | 44 |
| Least Squares Mean (80% Confidence Interval) [Percentage of participants] |
35.3
39.2%
|
36.0
65.5%
|
42.5
51.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.94 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 0.8 | |
| Confidence Interval |
(2-Sided) 80% -11.3 to 12.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.46 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 7.3 | |
| Confidence Interval |
(2-Sided) 80% -5.4 to 19.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in Previously Treated 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 up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm C: 6 mg Faricimab |
|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 28 | 23 |
| Least Squares Mean (80% Confidence Interval) [Percentage of participants] |
16.8
18.7%
|
23.2
42.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.56 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Percentage of Participants |
| Estimated Value | 6.4 | |
| Confidence Interval |
(2-Sided) 80% -7.7 to 20.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in All 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 up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 77 | 50 | 67 |
| Least Squares Mean (80% Confidence Interval) [Percentage of participants] |
28.7
31.9%
|
35.3
64.2%
|
35.9
43.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.43 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 6.6 | |
| Confidence Interval |
(2-Sided) 80% -4.0 to 17.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.34 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 7.2 | |
| Confidence Interval |
(2-Sided) 80% -2.6 to 17.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, 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 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 49 | 49 | 44 |
| Least Squares Mean (80% Confidence Interval) [Percentage of participants] |
69.0
76.7%
|
78.5
142.7%
|
75.8
92.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.27 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 9.5 | |
| Confidence Interval |
(2-Sided) 80% -1.6 to 20.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.45 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 6.8 | |
| Confidence Interval |
(2-Sided) 80% -4.9 to 18.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in Previously Treated 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 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm C: 6 mg Faricimab |
|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 28 | 23 |
| Least Squares Mean (80% Confidence Interval) [Percentage of participants] |
69.0
76.7%
|
68.4
124.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.96 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 80% -16.8 to 15.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in All 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 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 77 | 50 | 67 |
| Least Squares Mean (80% Confidence Interval) [Percentage of participants] |
69.0
76.7%
|
78.9
143.5%
|
73.2
89.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.19 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 9.9 | |
| Confidence Interval |
(2-Sided) 80% 0.1 to 19.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.57 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | 4.2 | |
| Confidence Interval |
(2-Sided) 80% -5.3 to 13.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, 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 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 49 | 49 | 44 |
| Least Squares Mean (80% Confidence Interval) [Percentage of participants] |
11.5
12.8%
|
8.7
15.8%
|
9.8
12%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.64 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -2.8 | |
| Confidence Interval |
(2-Sided) 80% -10.5 to 4.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.78 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 80% -9.8 to 6.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in Previously Treated 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 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm C: 6 mg Faricimab |
|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 28 | 23 |
| Least Squares Mean (80% Confidence Interval) [Percentage of participants] |
10.5
11.7%
|
8.2
14.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.78 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -2.3 | |
| Confidence Interval |
(2-Sided) 80% -12.7 to 8.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in All 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 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 77 | 50 | 67 |
| Least Squares Mean (80% Confidence Interval) [Percentage of participants] |
11.1
12.3%
|
10.6
19.3%
|
9.1
11.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.93 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 80% -7.7 to 6.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.69 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Generalized Estimating Equations Model | |
| Comments | Categorical covariates: treatment group, visit, and visit by treatment group interaction term. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -2.0 | |
| Confidence Interval |
(2-Sided) 80% -8.3 to 4.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Change From Baseline in Foveal Center Point Thickness at Week 24, 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). |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 49 | 49 | 44 |
| Least Squares Mean (80% Confidence Interval) [micrometers] |
-243.4
|
-249.9
|
-266.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.69 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline FCPT. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -6.5 | |
| Confidence Interval |
(2-Sided) 80% -27.8 to 14.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.18 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline FCPT. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -22.8 | |
| Confidence Interval |
(2-Sided) 80% -44.5 to -1.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in Previously Treated 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). |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm C: 6 mg Faricimab |
|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 28 | 23 |
| Least Squares Mean (80% Confidence Interval) [micrometers] |
-162.1
|
-211.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.07 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline FCPT. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -49.2 | |
| Confidence Interval |
(2-Sided) 80% -84.2 to -14.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in All 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). |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 77 | 50 | 67 |
| Least Squares Mean (80% Confidence Interval) [micrometers] |
-210.7
|
-228.0
|
-239.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.28 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline FCPT. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -17.3 | |
| Confidence Interval |
(2-Sided) 80% -38.0 to 3.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.05 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline FCPT. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -29.2 | |
| Confidence Interval |
(2-Sided) 80% -47.8 to -10.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Change From Baseline in Central Subfield Thickness at Week 24, 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 SD-OCT. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 49 | 49 | 44 |
| Least Squares Mean (80% Confidence Interval) [micrometers] |
-204.7
|
-217.1
|
-225.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.36 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline CST. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -12.4 | |
| Confidence Interval |
(2-Sided) 80% -29.7 to 5.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.13 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline CST. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -21.1 | |
| Confidence Interval |
(2-Sided) 80% -38.7 to -3.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Change From Baseline in Central Subfield Thickness at Week 24, in Previously Treated 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 SD-OCT. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm C: 6 mg Faricimab |
|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 28 | 23 |
| Least Squares Mean (80% Confidence Interval) [micrometers] |
-148.0
|
-186.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.07 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline CST. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -38.6 | |
| Confidence Interval |
(2-Sided) 80% -65.9 to -11.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Mean Change From Baseline in Central Subfield Thickness at Week 24, in All 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 SD-OCT. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 77 | 50 | 67 |
| Least Squares Mean (80% Confidence Interval) [micrometers] |
-180.2
|
-200.3
|
-206.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.12 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline CST. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -20.1 | |
| Confidence Interval |
(2-Sided) 80% -36.4 to -3.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.02 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Mixed Effects Model of Repeated Measures | |
| Comments | Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline CST. | |
| Method of Estimation | Estimation Parameter | Difference in Least Squares Means |
| Estimated Value | -26.7 | |
| Confidence Interval |
(2-Sided) 80% -41.3 to -12.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference between arms was calculated as Arm C minus Arm A. | |
| Title | Percentage of Participants With Presence of Subretinal Fluid in the Study Eye at Week 24, in Treatment-Naive Participants |
|---|---|
| Description | Subretinal fluid is defined as the presence of fluid between the retina and the retinal pigment epithelium. Resolution of subretinal fluid was measured using SD-OCT. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 49 | 49 | 44 |
| Number (80% Confidence Interval) [Percentage of participants] |
4.08
4.5%
|
0.00
0%
|
0.00
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4948 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage of Participants |
| Estimated Value | -4.08 | |
| Confidence Interval |
(2-Sided) 80% -7.70 to -0.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The difference between arms was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4960 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage of Participants |
| Estimated Value | -4.08 | |
| Confidence Interval |
(2-Sided) 80% -7.70 to -0.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The difference between arms was calculated as Arm C minus Arm A. | |
| Title | Percentage of Participants With Presence of Subretinal Fluid in the Study Eye at Week 24, in Previously Treated Participants |
|---|---|
| Description | Subretinal fluid is defined as the presence of fluid between the retina and the retinal pigment epithelium. Resolution of subretinal fluid was measured using SD-OCT. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm C: 6 mg Faricimab |
|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 28 | 23 |
| Number (80% Confidence Interval) [Percentage of participants] |
7.14
7.9%
|
4.35
7.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage of Participants |
| Estimated Value | -2.80 | |
| Confidence Interval |
(2-Sided) 80% -11.08 to 5.49 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The difference between arms was calculated as Arm C minus Arm A. | |
| Title | Percentage of Participants With Presence of Intraretinal Fluid in the Study Eye at Week 24, in Treatment-Naive Participants |
|---|---|
| Description | Intraretinal fluid is described as the presence of fluid within the retina. Resolution of intraretinal fluid was measured by SD-OCT. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 49 | 49 | 44 |
| Number (80% Confidence Interval) [percentage of participants] |
87.76
97.5%
|
81.63
148.4%
|
90.91
110.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5759 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage of Participants |
| Estimated Value | -6.12 | |
| Confidence Interval |
(2-Sided) 80% -15.41 to 3.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The difference between arms was calculated as Arm B minus Arm A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7437 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage of Participants |
| Estimated Value | 3.15 | |
| Confidence Interval |
(2-Sided) 80% -5.02 to 11.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The difference between arms was calculated as Arm C minus Arm A. | |
| Title | Percentage of Participants With Presence of Intraretinal Fluid in the Study Eye at Week 24, in Previously Treated Participants |
|---|---|
| Description | Intraretinal fluid is described as the presence of fluid within the retina. Resolution of intraretinal fluid was measured by SD-OCT. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm C: 6 mg Faricimab |
|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 28 | 23 |
| Number (80% Confidence Interval) [percentage of participants] |
89.29
99.2%
|
91.30
166%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab |
|---|---|---|
| Comments | Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage of Participants |
| Estimated Value | 2.02 | |
| Confidence Interval |
(2-Sided) 80% -8.60 to 12.64 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The difference between arms was calculated as Arm C minus Arm A. | |
| Title | Number of Participants With Presence or Absence of Leakage at the Macula at Week 24, in Treatment-Naive Participants |
|---|---|
| Description | Leakage at the macula describes the leakage of fluorescein at the macula region as measured by fundus fluorescein angiography (FFA). |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 45 | 46 | 36 |
| Leakage Present |
41
45.6%
|
41
74.5%
|
25
30.5%
|
| Leakage Absent |
4
4.4%
|
5
9.1%
|
11
13.4%
|
| Title | Number of Participants With Presence or Absence of Leakage at the Macula at Week 24, in Previously Treated Participants |
|---|---|
| Description | Leakage at the macula describes the leakage of fluorescein at the macula region as measured by fundus fluorescein angiography (FFA). |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 25 | 1 | 16 |
| Leakage Present |
24
26.7%
|
1
1.8%
|
14
17.1%
|
| Leakage Absent |
1
1.1%
|
0
0%
|
2
2.4%
|
| Title | Mean Change From Baseline in the Size of the Foveal Avascular Zone at Week 24, in All Participants |
|---|---|
| Description | The size of the foveal avascular zone was to be measured by fundus fluorescein angiography (FFA). |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the poor image quality available, size of the foveal avascular zone could not be assessed in any of the participant populations. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 0 | 0 | 0 |
| Title | Mean Plasma Concentrations of Ranibizumab (Arm A) or Faricimab (Arms B and C) Over Time, in All Participants |
|---|---|
| Description | Plasma concentrations of ranibizumab were measured by an appropriate assay only from samples of participants randomized to Arm A: 0.3 mg Ranibizumab. Plasma concentrations of faricimab were measured by a specific validated enzyme-linked immunoabsorbent assay (ELISA) only from samples of participants randomized to Arm B: 1.5 mg Faricimab and Arm C: 6 mg Faricimab. Baseline was defined as the last non-missing predose assessment. The lower limit of quantification (LLOQ) for the ranibizumab and faricimab assays were 0.015 nanograms per millilitre (ng/mL) and 0.800 ng/mL, respectively. Values below the limit of quantification were imputed as LLOQ divided by 2. |
| Time Frame | Predose at Baseline and Weeks 1, 4, 12, 20, 24, 26, 28, 32, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics Population: The analysis included participants who received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study) and had plasma samples available at a given study visit timepoint. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 90 | 55 | 82 |
| Baseline |
2.20
(7.84)
|
0.40
(0.00)
|
0.40
(0.00)
|
| Week 1 |
2.52
(7.57)
|
48.36
(22.46)
|
172.24
(80.59)
|
| Week 4 |
0.86
(2.27)
|
6.97
(4.96)
|
20.60
(13.46)
|
| Week 12 |
0.26
(0.48)
|
9.32
(5.93)
|
22.38
(13.63)
|
| Week 20 |
0.21
(0.35)
|
7.11
(4.64)
|
22.59
(18.10)
|
| Week 24 |
0.20
(0.44)
|
8.69
(5.06)
|
20.18
(16.37)
|
| Week 26 |
0.19
(0.47)
|
3.80
(3.28)
|
8.18
(6.98)
|
| Week 28 |
0.10
(0.16)
|
1.44
(2.42)
|
2.94
(3.07)
|
| Week 32 |
0.05
(0.09)
|
0.46
(0.23)
|
0.82
(0.97)
|
| Week 36 |
0.03
(0.05)
|
0.40
(0.00)
|
0.40
(0.00)
|
| Title | Baseline and Change From Baseline in Free Vascular Endothelial Growth Factor (VEGF) Plasma Levels Over Time, in Treatment-Naive 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 and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics Population: The analysis included participants who received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study) and had plasma samples available at a given study visit timepoint. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 59 | 54 | 53 |
| Baseline (BL) - Value at Visit |
23.93
(52.75)
|
14.93
(19.70)
|
12.45
(7.62)
|
| Change from BL at Week 1 |
-9.44
(49.77)
|
-3.85
(20.99)
|
-3.61
(6.96)
|
| Change from BL at Week 4 |
-1.68
(21.20)
|
-0.37
(21.76)
|
-0.49
(9.31)
|
| Change from BL at Week 12 |
-3.54
(22.50)
|
-1.61
(20.82)
|
1.67
(16.69)
|
| Change from BL at Week 16 |
0.00
(NA)
|
||
| Change from BL at Week 24 |
-7.31
(23.97)
|
2.92
(18.23)
|
2.83
(13.74)
|
| Change from BL at Week 26 |
-4.37
(13.09)
|
-2.98
(6.27)
|
-2.43
(7.08)
|
| Change from BL at Week 28 |
0.30
(5.87)
|
0.73
(12.17)
|
7.15
(7.73)
|
| Change from BL at Week 32 |
-3.30
(8.13)
|
-35.85
(65.08)
|
4.50
(5.97)
|
| Change from BL at Week 36 |
-1.75
(14.00)
|
0.69
(7.71)
|
2.07
(10.38)
|
| Title | Baseline and Change From Baseline in Free Vascular Endothelial Growth Factor (VEGF) Plasma Levels Over Time, in Previously Treated 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 and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics Population: The analysis included participants who received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study) and had plasma samples available at a given study visit timepoint. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 31 | 1 | 29 |
| Baseline (BL) - Value at Visit |
12.94
(10.00)
|
7.80
(NA)
|
16.21
(10.22)
|
| Change from BL at Week 1 |
0.50
(14.24)
|
8.20
(NA)
|
-7.40
(12.08)
|
| Change from BL at Week 4 |
0.93
(15.07)
|
14.50
(NA)
|
-0.80
(11.11)
|
| Change from BL at Week 12 |
13.83
(51.87)
|
39.20
(NA)
|
0.78
(16.55)
|
| Change from BL at Week 16 |
19.10
(NA)
|
||
| Change from BL at Week 24 |
6.60
(31.50)
|
12.40
(NA)
|
4.13
(27.51)
|
| Change from BL at Week 26 |
-0.25
(13.97)
|
16.65
(42.34)
|
|
| Change from BL at Week 28 |
7.32
(20.30)
|
0.00
(0.00)
|
|
| Change from BL at Week 32 |
-1.13
(11.24)
|
57.00
(NA)
|
|
| Change from BL at Week 36 |
3.05
(11.44)
|
21.50
(NA)
|
3.53
(21.58)
|
| Title | Baseline and Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Treatment-Naive 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 and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics Population: The analysis included participants who received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study) and had plasma samples available at a given study visit timepoint. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 59 | 54 | 53 |
| Baseline (BL) - Value at Visit |
2.77
(2.01)
|
2.07
(0.91)
|
2.30
(1.88)
|
| Change from BL at Week 1 |
0.07
(0.60)
|
0.04
(0.80)
|
0.75
(0.79)
|
| Change from BL at Week 4 |
0.14
(0.72)
|
0.05
(0.63)
|
0.24
(0.79)
|
| Change from BL at Week 12 |
0.06
(0.66)
|
0.14
(0.51)
|
0.18
(1.02)
|
| Change from BL at Week 16 |
-0.08
(NA)
|
||
| Change from BL at Week 24 |
0.30
(0.80)
|
0.40
(0.90)
|
0.00
(0.61)
|
| Change from BL at Week 26 |
0.25
(1.37)
|
0.21
(0.33)
|
0.58
(0.78)
|
| Change from BL at Week 28 |
0.11
(0.35)
|
0.34
(0.35)
|
-0.20
(0.49)
|
| Change from BL at Week 32 |
-0.35
(0.50)
|
1.58
(1.91)
|
0.42
(0.21)
|
| Change from BL at Week 36 |
0.05
(0.83)
|
0.39
(1.45)
|
-0.02
(0.83)
|
| Title | Baseline and Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Treatment-Naive 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 and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics Population: The analysis included participants who received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study) and had plasma samples available at a given study visit timepoint. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 59 | 54 | 53 |
| Baseline (BL) - Value at Visit |
3.05
(1.72)
|
2.38
(1.04)
|
2.46
(1.37)
|
| Change from BL at Week 1 |
-0.49
(0.46)
|
-0.59
(0.79)
|
0.06
(1.01)
|
| Change from BL at Week 4 |
-0.36
(0.66)
|
-0.45
(0.72)
|
-0.22
(0.88)
|
| Change from BL at Week 12 |
-0.07
(0.87)
|
0.10
(0.68)
|
0.25
(1.11)
|
| Change from BL at Week 16 |
-0.74
(NA)
|
||
| Change from BL at Week 24 |
-0.08
(0.95)
|
0.19
(1.14)
|
-0.11
(0.86)
|
| Change from BL at Week 26 |
-0.23
(1.27)
|
-0.26
(0.39)
|
0.08
(0.76)
|
| Change from BL at Week 28 |
-0.56
(0.69)
|
-0.37
(0.44)
|
-0.54
(0.60)
|
| Change from BL at Week 32 |
-0.61
(0.58)
|
0.92
(1.83)
|
-0.12
(0.28)
|
| Change from BL at Week 36 |
-0.61
(0.87)
|
-0.15
(1.03)
|
-0.26
(0.89)
|
| Title | Baseline and Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Previously Treated 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 and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics Population: The analysis included participants who received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study) and had plasma samples available at a given study visit timepoint. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 31 | 1 | 29 |
| Baseline (BL) - Value at Visit |
2.40
(2.34)
|
1.84
(NA)
|
2.31
(1.78)
|
| Change from BL at Week 1 |
0.15
(14.24)
|
0.11
(NA)
|
0.94
(1.12)
|
| Change from BL at Week 4 |
0.03
(0.52)
|
-0.27
(NA)
|
0.14
(0.87)
|
| Change from BL at Week 12 |
0.33
(1.66)
|
-0.28
(NA)
|
-0.09
(0.46)
|
| Change from BL at Week 16 |
-0.21
(NA)
|
||
| Change from BL at Week 24 |
0.19
(1.22)
|
-0.19
(NA)
|
-0.16
(0.46)
|
| Change from BL at Week 26 |
-0.07
(0.64)
|
-0.20
(0.42)
|
|
| Change from BL at Week 28 |
0.74
(2.78)
|
-0.91
(0.35)
|
|
| Change from BL at Week 32 |
-0.04
(0.79)
|
0.49
(NA)
|
|
| Change from BL at Week 36 |
0.01
(0.72)
|
-0.47
(NA)
|
-0.13
(0.42)
|
| Title | Baseline and Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Previously Treated 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 and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics Population: The analysis included participants who received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study) and had plasma samples available at a given study visit timepoint. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 31 | 1 | 29 |
| Baseline (BL) - Value at Visit |
2.67
(2.60)
|
2.08
(NA)
|
2.35
(1.76)
|
| Change from BL at Week 1 |
-0.07
(0.88)
|
-0.04
(NA)
|
0.30
(0.87)
|
| Change from BL at Week 4 |
-0.33
(0.58)
|
-0.28
(NA)
|
-0.17
(0.66)
|
| Change from BL at Week 12 |
-0.05
(1.12)
|
-0.65
(NA)
|
-0.13
(0.61)
|
| Change from BL at Week 16 |
-0.49
(NA)
|
||
| Change from BL at Week 24 |
-0.28
(0.58)
|
-0.49
(NA)
|
-0.29
(0.64)
|
| Change from BL at Week 26 |
-0.21
(0.79)
|
-0.16
(0.54)
|
|
| Change from BL at Week 28 |
-0.17
(1.59)
|
-1.36
(0.83)
|
|
| Change from BL at Week 32 |
-0.59
(0.68)
|
0.07
(NA)
|
|
| Change from BL at Week 36 |
-0.29
(0.72)
|
-0.72
(NA)
|
-0.19
(0.45)
|
| Title | Safety Summary of the Number of Participants With at Least One Adverse Event During the Treatment Period (up to Week 24), in All Participants |
|---|---|
| Description | This safety summary reports the number and percentage of participants who experienced at least one adverse event (AE) within 28 days of the end of the treatment period (i.e., up to Week 24). 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 of treatment with study drug, and AEs with fatal outcome. Multiple occurrences of the same AE in one individual were counted only once. |
| Time Frame | From Baseline up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who had received at least one dose of the study drug, whether prematurely withdrawn from the study or not, grouped according to the actual treatment received. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 89 | 55 | 80 |
| Any AE |
61
67.8%
|
38
69.1%
|
54
65.9%
|
| Ocular AE |
30
33.3%
|
21
38.2%
|
32
39%
|
| Ocular AE in the Study Eye |
22
24.4%
|
16
29.1%
|
22
26.8%
|
| Related Ocular AE in the Study Eye |
1
1.1%
|
0
0%
|
2
2.4%
|
| Ocular AE in Study Eye Leading to Discontinuation |
1
1.1%
|
0
0%
|
0
0%
|
| Serious Ocular AE in the Study Eye |
1
1.1%
|
0
0%
|
1
1.2%
|
| Ocular AE in the Fellow Eye |
19
21.1%
|
14
25.5%
|
18
22%
|
| Systemic AE |
51
56.7%
|
30
54.5%
|
46
56.1%
|
| Related Systemic AE |
0
0%
|
0
0%
|
2
2.4%
|
| Serious Systemic AE |
8
8.9%
|
6
10.9%
|
7
8.5%
|
| Systemic AE Leading to Discontinuation |
0
0%
|
1
1.8%
|
0
0%
|
| Any Related AE |
1
1.1%
|
0
0%
|
4
4.9%
|
| Any Serious AE |
9
10%
|
7
12.7%
|
8
9.8%
|
| Any Related Serious AE |
0
0%
|
0
0%
|
0
0%
|
| AE with Fatal Outcome |
2
2.2%
|
1
1.8%
|
2
2.4%
|
| Title | Safety Summary of the Number of Participants With at Least One Adverse Event During the Post-Treatment Observation Period, in All Participants |
|---|---|
| Description | This safety summary reports the number and percentage of participants who experienced at least one adverse event (AE) during the post-treatment observation period (i.e., from Week 24 up to Week 36). 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 of treatment with study drug, and AEs with fatal outcome. Multiple occurrences of the same AE in one individual were counted only once. |
| Time Frame | From Week 24 up to Week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who had received at least one dose of the study drug, whether prematurely withdrawn from the study or not, grouped according to the actual treatment received. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 89 | 55 | 80 |
| Any AE |
31
34.4%
|
21
38.2%
|
34
41.5%
|
| Ocular AE |
11
12.2%
|
7
12.7%
|
12
14.6%
|
| Ocular AE in the Study Eye |
9
10%
|
4
7.3%
|
8
9.8%
|
| Related Ocular AE in the Study Eye |
1
1.1%
|
0
0%
|
0
0%
|
| Ocular AE in Study Eye Leading to Discontinuation |
0
0%
|
0
0%
|
0
0%
|
| Serious Ocular AE in the Study Eye |
0
0%
|
0
0%
|
1
1.2%
|
| Ocular AE in the Fellow Eye |
6
6.7%
|
5
9.1%
|
8
9.8%
|
| Systemic AE |
22
24.4%
|
15
27.3%
|
25
30.5%
|
| Related Systemic AE |
0
0%
|
0
0%
|
0
0%
|
| Serious Systemic AE |
2
2.2%
|
3
5.5%
|
4
4.9%
|
| Systemic AE Leading to Discontinuation |
0
0%
|
0
0%
|
0
0%
|
| Any Related AE |
1
1.1%
|
0
0%
|
0
0%
|
| Any Serious AE |
2
2.2%
|
3
5.5%
|
5
6.1%
|
| Any Related Serious AE |
0
0%
|
0
0%
|
0
0%
|
| AE with Fatal Outcome |
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 During the Treatment Period 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 up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who had received at least one dose of the study drug, whether prematurely withdrawn from the study or not, grouped according to the actual treatment received. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 89 | 55 | 80 |
| Study Eye - Ocular AE of Any Intensity |
22
24.4%
|
16
29.1%
|
22
26.8%
|
| Study Eye - Mild Ocluar AE |
20
22.2%
|
15
27.3%
|
21
25.6%
|
| Study Eye - Moderate Ocular AE |
2
2.2%
|
3
5.5%
|
3
3.7%
|
| Study Eye - Severe Ocular AE |
1
1.1%
|
0
0%
|
0
0%
|
| Fellow Eye - Ocular AE of Any Intensity |
19
21.1%
|
14
25.5%
|
18
22%
|
| Fellow Eye - Mild Ocular AE |
13
14.4%
|
13
23.6%
|
14
17.1%
|
| Fellow Eye - Moderate Ocular AE |
7
7.8%
|
1
1.8%
|
5
6.1%
|
| Fellow Eye - Severe Ocular AE |
0
0%
|
1
1.8%
|
0
0%
|
| Title | Number of Participants With at Least One Systemic Adverse Event During the Treatment Period 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 up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who had received at least one dose of the study drug, whether prematurely withdrawn from the study or not, grouped according to the actual treatment received. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 89 | 55 | 80 |
| Systemic AE of Any Intensity |
51
56.7%
|
30
54.5%
|
46
56.1%
|
| Mild Systemic AE |
34
37.8%
|
19
34.5%
|
34
41.5%
|
| Moderate Systemic AE |
26
28.9%
|
18
32.7%
|
22
26.8%
|
| Severe Systemic AE |
9
10%
|
4
7.3%
|
5
6.1%
|
| Title | Number of Participants With Abnormal Systolic Blood Pressure Over Time, in All Participants |
|---|---|
| Description | Abnormal systolic blood pressure (supine) was defined as any value outside of the standard reference range, from <70 (low) to >180 (high) millimetres of mercury (mmHg) or a change from baseline of greater than 30 mmHg (decrease or increase). 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 | Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population; 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 and who were evaluable at a given assessment timepoint. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 89 | 55 | 80 |
| Week 1 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 1 - High |
1
1.1%
|
3
5.5%
|
0
0%
|
| Week 4 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 4 - High |
0
0%
|
0
0%
|
1
1.2%
|
| Week 8 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 8 - High |
1
1.1%
|
0
0%
|
2
2.4%
|
| Week 12 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 12 - High |
1
1.1%
|
0
0%
|
2
2.4%
|
| Week 16 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 16 - High |
0
0%
|
1
1.8%
|
1
1.2%
|
| Week 20 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 20 - High |
3
3.3%
|
2
3.6%
|
3
3.7%
|
| Week 24 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 24 - High |
2
2.2%
|
2
3.6%
|
2
2.4%
|
| Week 26 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 26 - High |
0
0%
|
0
0%
|
0
0%
|
| Week 28 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 28 - High |
1
1.1%
|
1
1.8%
|
1
1.2%
|
| Week 32 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 32 - High |
4
4.4%
|
1
1.8%
|
2
2.4%
|
| Week 36 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 36 - High |
1
1.1%
|
0
0%
|
2
2.4%
|
| Title | Number of Participants With Abnormal Diastolic Blood Pressure Over Time, in All Participants |
|---|---|
| Description | Abnormal diastolic blood pressure (supine) was defined as any value outside of the standard reference range, from <40 (low) to >110 (high) millimetres of mercury (mmHg) or a change from baseline of greater than 20 mmHg (decrease or increase). 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 | Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population; 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 and who were evaluable at a given assessment timepoint. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 89 | 55 | 80 |
| Week 1 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 1 - High |
1
1.1%
|
0
0%
|
0
0%
|
| Week 4 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 4 - High |
0
0%
|
0
0%
|
0
0%
|
| Week 8 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 8 - High |
0
0%
|
0
0%
|
0
0%
|
| Week 12 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 12 - High |
0
0%
|
0
0%
|
2
2.4%
|
| Week 16 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 16 - High |
0
0%
|
0
0%
|
0
0%
|
| Week 20 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 20 - High |
1
1.1%
|
0
0%
|
1
1.2%
|
| Week 24 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 24 - High |
1
1.1%
|
0
0%
|
0
0%
|
| Week 26 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 26 - High |
1
1.1%
|
0
0%
|
0
0%
|
| Week 28 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 28 - High |
0
0%
|
0
0%
|
0
0%
|
| Week 32 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 32 - High |
1
1.1%
|
1
1.8%
|
0
0%
|
| Week 36 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 36 - High |
0
0%
|
0
0%
|
1
1.2%
|
| Title | Number of Participants With an Abnormal Heart Rate Over Time, 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 | Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population; 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 and who were evaluable at a given assessment timepoint. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 89 | 55 | 80 |
| Week 1 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 1 - High |
0
0%
|
0
0%
|
1
1.2%
|
| Week 4 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 4 - High |
1
1.1%
|
0
0%
|
0
0%
|
| Week 8 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 8 - High |
0
0%
|
0
0%
|
0
0%
|
| Week 12 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 12 - High |
1
1.1%
|
0
0%
|
1
1.2%
|
| Week 16 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 16 - High |
2
2.2%
|
0
0%
|
3
3.7%
|
| Week 20 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 20 - High |
1
1.1%
|
0
0%
|
1
1.2%
|
| Week 24 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 24 - High |
1
1.1%
|
0
0%
|
2
2.4%
|
| Week 26 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 26 - High |
2
2.2%
|
0
0%
|
1
1.2%
|
| Week 28 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 28 - High |
0
0%
|
0
0%
|
2
2.4%
|
| Week 32 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 32 - High |
1
1.1%
|
0
0%
|
0
0%
|
| Week 36 - Low |
0
0%
|
0
0%
|
0
0%
|
| Week 36 - High |
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Abnormal Body Temperature Over Time, 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 | Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population; 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 and who were evaluable at a given assessment timepoint. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 89 | 55 | 80 |
| Week 1 - Low |
8
8.9%
|
4
7.3%
|
7
8.5%
|
| Week 1 - High |
0
0%
|
0
0%
|
1
1.2%
|
| Week 4 - Low |
13
14.4%
|
2
3.6%
|
8
9.8%
|
| Week 4 - High |
0
0%
|
1
1.8%
|
0
0%
|
| Week 8 - Low |
14
15.6%
|
4
7.3%
|
9
11%
|
| Week 8 - High |
1
1.1%
|
1
1.8%
|
1
1.2%
|
| Week 12 - Low |
9
10%
|
4
7.3%
|
14
17.1%
|
| Week 12 - High |
1
1.1%
|
1
1.8%
|
0
0%
|
| Week 16 - Low |
5
5.6%
|
3
5.5%
|
13
15.9%
|
| Week 16 - High |
1
1.1%
|
1
1.8%
|
0
0%
|
| Week 20 - Low |
8
8.9%
|
6
10.9%
|
7
8.5%
|
| Week 20 - High |
0
0%
|
0
0%
|
0
0%
|
| Week 24 - Low |
13
14.4%
|
6
10.9%
|
10
12.2%
|
| Week 24 - High |
0
0%
|
0
0%
|
1
1.2%
|
| Week 26 - Low |
3
3.3%
|
1
1.8%
|
5
6.1%
|
| Week 26 - High |
1
1.1%
|
0
0%
|
1
1.2%
|
| Week 28 - Low |
11
12.2%
|
4
7.3%
|
10
12.2%
|
| Week 28 - High |
0
0%
|
0
0%
|
1
1.2%
|
| Week 32 - Low |
7
7.8%
|
7
12.7%
|
9
11%
|
| Week 32 - High |
1
1.1%
|
0
0%
|
0
0%
|
| Week 36 - Low |
5
5.6%
|
7
12.7%
|
8
9.8%
|
| Week 36 - High |
0
0%
|
0
0%
|
0
0%
|
| Title | Mean Heart Rate at Baseline and Week 24, as Measured by Electrocardiogram in All Participants |
|---|---|
| Description | Triplicate 12-lead electrocardiogram (ECG), i.e., three useful ECGs without artifacts, were performed on all evaluable participants. To minimize variability, it was important that participants be in a resting position for at least 10 minutes prior to the ECG evaluation. Body position was to be consistently maintained for each ECG evaluation to prevent changes in heart rate. Environmental distractions (e.g., television, radio, conversation, mobile phones) were to be minimized before and during ECG recording. Triplicate ECGs were to be obtained within a 5-minute interval. The predefined standard reference range for heart rate measured by ECG was 40 (low) to 100 (high) beats per minute. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who had received at least one dose of the study drug, whether prematurely withdrawn from the study or not, grouped according to the actual treatment received. This analysis included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 89 | 55 | 80 |
| Baseline |
71.52
(14.47)
|
73.65
(10.43)
|
74.12
(12.89)
|
| Week 24 |
71.12
(12.53)
|
73.96
(11.32)
|
75.61
(11.46)
|
| Title | Mean PR, RR, QT, QRS, QTcB, and QTcF Intervals at Baseline and Week 24, as Measured by Electrocardiogram in All Participants |
|---|---|
| Description | Triplicate 12-lead electrocardiogram (ECG), i.e., three useful ECGs without artifacts, were performed on all evaluable participants. To minimize variability, it was important that participants be in a resting position for at least 10 minutes prior to the ECG evaluation. Body position was to be consistently maintained for each ECG evaluation to prevent changes in heart rate. Environmental distractions (e.g., television, radio, conversation, mobile phones) were to be minimized before and during ECG recording. Triplicate ECGs were to be obtained within a 5-minute interval. Baseline was defined as the last non-missing predose assessment. The predefined standard reference ranges for the intervals measured by ECG were defined as follows (ranges are from low to high, in milliseconds [msec]): PR: 120-200 msec; RR: 600-1500 msec; QT: 200-500 msec; QRS: 40-120 msec. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who had received at least one dose of the study drug, whether prematurely withdrawn from the study or not, grouped according to the actual treatment received. This analysis included participants with non-missing assessments at Baseline and Week 24. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 89 | 55 | 80 |
| PR Interval at Baseline |
172.57
(28.62)
|
168.50
(31.82)
|
170.91
(29.06)
|
| PR Interval at Week 24 |
171.95
(30.21)
|
167.49
(26.20)
|
172.02
(28.81)
|
| RR Interval at Baseline |
864.44
(160.30)
|
826.04
(119.67)
|
828.64
(146.42)
|
| RR Interval at Week 24 |
864.34
(154.93)
|
824.13
(126.72)
|
806.45
(124.82)
|
| QT Interval at Baseline |
395.40
(40.47)
|
387.87
(30.52)
|
386.97
(32.65)
|
| QT Interval at Week 24 |
393.96
(36.74)
|
384.30
(28.03)
|
381.50
(28.10)
|
| QRS Interval at Baseline |
98.84
(19.80)
|
96.06
(16.76)
|
95.26
(15.54)
|
| QRS Interval at Week 24 |
98.82
(19.90)
|
96.66
(11.24)
|
95.40
(17.83)
|
| QTcB Interval at Baseline |
426.98
(24.47)
|
427.85
(24.33)
|
426.91
(22.84)
|
| QTcB Interval at Week 24 |
425.60
(25.55)
|
424.79
(22.93)
|
426.31
(23.36)
|
| QTcF Interval at Baseline |
415.60
(25.63)
|
413.61
(23.15)
|
412.67
(21.17)
|
| QTcF Interval at Week 24 |
414.21
(24.75)
|
410.45
(20.35)
|
410.42
(20.61)
|
| Title | Number of Participants With Marked Laboratory Abnormalities in Hematology Tests, in All Participants |
|---|---|
| Description | Clinical laboratory tests for hematology 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; Ery. = erythrocyte; Hemo. = hemoglobin |
| Time Frame | Predose at Baseline, Weeks 12 and 24, and at Early Termination and Unscheduled Visits (up to 36 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who had received at least one dose of the study drug, whether prematurely withdrawn from the study or not, grouped according to the actual treatment received. This analysis included participants with non-missing assessments. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 89 | 55 | 80 |
| Eosinophils, Abs., High - Any Abnormality |
2
2.2%
|
1
1.8%
|
3
3.7%
|
| Eosinophils, Abs., High - Single, Not Last |
1
1.1%
|
1
1.8%
|
3
3.7%
|
| Eosinophils, Abs., High - Last or Replicated |
1
1.1%
|
0
0%
|
0
0%
|
| Hematocrit, Low - Any Abnormality |
4
4.4%
|
1
1.8%
|
1
1.2%
|
| Hematocrit, Low - Single, Not Last |
1
1.1%
|
0
0%
|
1
1.2%
|
| Hematocrit, Low - Last or Replicated |
3
3.3%
|
1
1.8%
|
0
0%
|
| Hemoglobin, Low - Any Abnormality |
4
4.4%
|
1
1.8%
|
2
2.4%
|
| Hemoglobin, Low - Single, Not Last |
1
1.1%
|
0
0%
|
2
2.4%
|
| Hemoglobin, Low - Last or Replicated |
3
3.3%
|
1
1.8%
|
0
0%
|
| Lymphocytes, Abs., Low - Any Abnormality |
1
1.1%
|
0
0%
|
1
1.2%
|
| Lymphocytes, Abs., Low - Single, Not Last |
1
1.1%
|
0
0%
|
1
1.2%
|
| Lymphocytes, Abs., Low - Last or Replicated |
0
0%
|
0
0%
|
0
0%
|
| Ery. Mean Corpuscular Hemo., Low - Any Abnormality |
0
0%
|
0
0%
|
1
1.2%
|
| Ery. Mean Corpuscular Hemo., Low -Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
| Ery. Mean Corpuscular Hemo.,Low-Last or Replicated |
0
0%
|
0
0%
|
1
1.2%
|
| Neutrophils, Total, Abs., Low - Any Abnormality |
1
1.1%
|
1
1.8%
|
0
0%
|
| Neutrophils, Total, Abs., Low - Single, Not Last |
1
1.1%
|
0
0%
|
0
0%
|
| Neutrophils, Total, Abs., Low -Last or Replicated |
0
0%
|
1
1.8%
|
0
0%
|
| Neutrophils, Total, Abs., High - Any Abnormality |
2
2.2%
|
0
0%
|
2
2.4%
|
| Neutrophils, Total, Abs., High - Single, Not Last |
1
1.1%
|
0
0%
|
0
0%
|
| Neutrophils, Total, Abs., High -Last or Replicated |
1
1.1%
|
0
0%
|
2
2.4%
|
| Platelets, Low - Any Abnormality |
1
1.1%
|
1
1.8%
|
0
0%
|
| Platelets, Low - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
| Platelets, Low - Last or Replicated |
1
1.1%
|
1
1.8%
|
0
0%
|
| Platelets, High - Any Abnormality |
1
1.1%
|
0
0%
|
0
0%
|
| Platelets, High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
| Platelets, High - Last or Replicated |
1
1.1%
|
0
0%
|
0
0%
|
| Red Blood Cell Count, Low - Any Abnormality |
3
3.3%
|
1
1.8%
|
1
1.2%
|
| Red Blood Cell Count, Low - Single, Not Last |
2
2.2%
|
0
0%
|
1
1.2%
|
| Red Blood Cell Count, Low - Last or Replicated |
1
1.1%
|
1
1.8%
|
0
0%
|
| White Blood Cell Count, Low - Any Abnormality |
1
1.1%
|
2
3.6%
|
1
1.2%
|
| White Blood Cell Count, Low - Single, Not Last |
1
1.1%
|
1
1.8%
|
1
1.2%
|
| White Blood Cell Count, Low - Last or Replicated |
0
0%
|
1
1.8%
|
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. SGOT/AST = serum glutamic oxaloacetic transaminase / aspartate aminotransferase |
| Time Frame | Predose at Baseline, Weeks 12 and 24, and at Early Termination and Unscheduled Visits (up to 36 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who had received at least one dose of the study drug, whether prematurely withdrawn from the study or not, grouped according to the actual treatment received. This analysis included participants with non-missing assessments. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 89 | 55 | 80 |
| Alkaline Phosphatase, High - Any Abnormality |
0
0%
|
0
0%
|
1
1.2%
|
| Alkaline Phosphatase, High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
| Alkaline Phosphatase, High - Last or Replicated |
0
0%
|
0
0%
|
1
1.2%
|
| SGOT/AST, High - Any Abnormality |
0
0%
|
1
1.8%
|
0
0%
|
| SGOT/AST, High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
| SGOT/AST, High - Last or Replicated |
0
0%
|
1
1.8%
|
0
0%
|
| Bicarbonate, Low - Any Abnormality |
4
4.4%
|
1
1.8%
|
2
2.4%
|
| Bicarbonate, Low - Single, Not Last |
0
0%
|
0
0%
|
1
1.2%
|
| Bicarbonate, Low - Last or Replicated |
4
4.4%
|
1
1.8%
|
1
1.2%
|
| Bicarbonate, High - Any Abnormality |
1
1.1%
|
0
0%
|
1
1.2%
|
| Bicarbonate, High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
| Bicarbonate, High - Last or Replicated |
1
1.1%
|
0
0%
|
1
1.2%
|
| Blood Urea Nitrogen, High - Any Abnormality |
2
2.2%
|
3
5.5%
|
3
3.7%
|
| Blood Urea Nitrogen, High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
| Blood Urea Nitrogen, High - Last or Replicated |
2
2.2%
|
3
5.5%
|
3
3.7%
|
| Calcium, Low - Any Abnormality |
2
2.2%
|
0
0%
|
2
2.4%
|
| Calcium, Low - Single, Not Last |
1
1.1%
|
0
0%
|
1
1.2%
|
| Calcium, Low - Last or Replicated |
1
1.1%
|
0
0%
|
1
1.2%
|
| Chloride, Low - Any Abnormality |
3
3.3%
|
1
1.8%
|
0
0%
|
| Chloride, Low - Single, Not Last |
2
2.2%
|
1
1.8%
|
0
0%
|
| Chloride, Low - Last or Replicated |
1
1.1%
|
0
0%
|
0
0%
|
| Cholesterol, High - Any Abnormality |
0
0%
|
1
1.8%
|
0
0%
|
| Cholesterol, High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
| Cholesterol, High - Last or Replicated |
0
0%
|
1
1.8%
|
0
0%
|
| Creatine Kinase, High - Any Abnormality |
3
3.3%
|
0
0%
|
1
1.2%
|
| Creatine Kinase, High - Single, Not Last |
1
1.1%
|
0
0%
|
1
1.2%
|
| Creatine Kinase, High - Last or Replicated |
2
2.2%
|
0
0%
|
0
0%
|
| Creatinine, High - Any Abnormality |
1
1.1%
|
0
0%
|
2
2.4%
|
| Creatinine, High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
| Creatinine, High - Last or Replicated |
1
1.1%
|
0
0%
|
2
2.4%
|
| Gamma Glutamyl Transferase, High-Any Abnormality |
3
3.3%
|
0
0%
|
2
2.4%
|
| Gamma Glutamyl Transferase, High-Single, Not Last |
1
1.1%
|
0
0%
|
0
0%
|
| Gamma Glutamyl Transferase,High-Last or Replicated |
2
2.2%
|
0
0%
|
2
2.4%
|
| Phosphorus, Low - Any Abnormality |
0
0%
|
1
1.8%
|
1
1.2%
|
| Phosphorus, Low - Single, Not Last |
0
0%
|
1
1.8%
|
0
0%
|
| Phosphorus, Low - Last or Replicated |
0
0%
|
0
0%
|
1
1.2%
|
| Phosphorus, High - Any Abnormality |
3
3.3%
|
0
0%
|
1
1.2%
|
| Phosphorus, High - Single, Not Last |
2
2.2%
|
0
0%
|
0
0%
|
| Phosphorus, High - Last or Replicated |
1
1.1%
|
0
0%
|
1
1.2%
|
| Potassium, High - Any Abnormality |
1
1.1%
|
0
0%
|
1
1.2%
|
| Potassium, High - Single, Not Last |
0
0%
|
0
0%
|
1
1.2%
|
| Potassium, High - Last or Replicated |
1
1.1%
|
0
0%
|
0
0%
|
| Sodium, Low - Any Abnormality |
1
1.1%
|
0
0%
|
0
0%
|
| Sodium, Low - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
| Sodium, Low - Last or Replicated |
1
1.1%
|
0
0%
|
0
0%
|
| Bilirubin, High - Any Abnormality |
0
0%
|
0
0%
|
1
1.2%
|
| Bilirubin, High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
| Bilirubin, High - Last or Replicated |
0
0%
|
0
0%
|
1
1.2%
|
| Protein, Total, Low - Any Abnormality |
0
0%
|
0
0%
|
1
1.2%
|
| Protein, Total, Low - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
| Protein, Total, Low - Last or Replicated |
0
0%
|
0
0%
|
1
1.2%
|
| Title | Number of Participants With Marked Laboratory Abnormalities in Coagulation Tests, in All Participants |
|---|---|
| Description | Clinical laboratory tests for 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. aPTT = activated partial thromboplastin time; INR = International Normalized Ratio (prothrombin time) |
| Time Frame | Predose at Baseline, Weeks 12 and 24, and at Early Termination and Unscheduled Visits (up to 36 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who had received at least one dose of the study drug, whether prematurely withdrawn from the study or not, grouped according to the actual treatment received. This analysis included participants with non-missing assessments. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 89 | 55 | 80 |
| INR, High - Any Abnormality |
1
1.1%
|
0
0%
|
0
0%
|
| INR, High - Single, Not Last |
0
0%
|
0
0%
|
0
0%
|
| INR, High - Last or Replicated |
1
1.1%
|
0
0%
|
0
0%
|
| aPTT, High - Any Abnormality |
5
5.6%
|
1
1.8%
|
1
1.2%
|
| aPTT, High - Single, Not Last |
2
2.2%
|
0
0%
|
0
0%
|
| aPTT, High - Last or Replicated |
3
3.3%
|
1
1.8%
|
1
1.2%
|
| Title | Number of Participants Who Tested Negative or Positive for Anti-Drug Antibodies Against Faricimab Over Time |
|---|---|
| Description | The number and percentage of participants who tested negative or positive for plasma anti-drug antibodies (ADA) to faricimab at baseline and at the study visits was tabulated, except for those who were randomized to treatment with ranibizumab in Arm A. |
| Time Frame | Baseline and Weeks 1, 4, 12, 16, 20, 24, 26, 28, 32, and 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who had received at least one dose of the study drug, whether prematurely withdrawn from the study or not, grouped according to the actual treatment received. Analysis only included participants who were randomized to treatment with faricimab in Arms B and C. |
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab |
|---|---|---|---|
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. |
| Measure Participants | 0 | 55 | 80 |
| Baseline - ADA Negative |
53
58.9%
|
75
136.4%
|
|
| Baseline - ADA Positive |
1
1.1%
|
2
3.6%
|
|
| Week 1 - ADA Negative |
50
55.6%
|
67
121.8%
|
|
| Week 1 - ADA Positive |
2
2.2%
|
1
1.8%
|
|
| Week 4 - ADA Negative |
52
57.8%
|
74
134.5%
|
|
| Week 4 - ADA Positive |
1
1.1%
|
2
3.6%
|
|
| Week 12 - ADA Negative |
49
54.4%
|
68
123.6%
|
|
| Week 12 - ADA Positive |
2
2.2%
|
3
5.5%
|
|
| Week 16 - ADA Negative |
1
1.1%
|
1
1.8%
|
|
| Week 16 - ADA Positive |
0
0%
|
0
0%
|
|
| Week 20 - ADA Negative |
50
55.6%
|
65
118.2%
|
|
| Week 20 - ADA Positive |
2
2.2%
|
5
9.1%
|
|
| Week 24 - ADA Negative |
46
51.1%
|
58
105.5%
|
|
| Week 24 - ADA Positive |
3
3.3%
|
6
10.9%
|
|
| Week 26 - ADA Negative |
2
2.2%
|
5
9.1%
|
|
| Week 26 - ADA Positive |
0
0%
|
0
0%
|
|
| Week 28 - ADA Negative |
6
6.7%
|
7
12.7%
|
|
| Week 28 - ADA Positive |
0
0%
|
0
0%
|
|
| Week 32 - ADA Negative |
5
5.6%
|
5
9.1%
|
|
| Week 32 - ADA Positive |
0
0%
|
0
0%
|
|
| Week 36 - ADA Negative |
32
35.6%
|
47
85.5%
|
|
| Week 36 - ADA Positive |
4
4.4%
|
6
10.9%
|
Adverse Events
| Time Frame | From Baseline until the final study visit (up to 36 weeks) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab | |||
| Arm/Group Description | Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. | |||
All Cause Mortality |
||||||
| Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/89 (2.2%) | 1/55 (1.8%) | 2/80 (2.5%) | |||
Serious Adverse Events |
||||||
| Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/89 (10.1%) | 7/55 (12.7%) | 8/80 (10%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Cardiac disorders | ||||||
| Acute left ventricular failure | 1/89 (1.1%) | 0/55 (0%) | 0/80 (0%) | |||
| Angina pectoris | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Cardiac arrest | 1/89 (1.1%) | 0/55 (0%) | 0/80 (0%) | |||
| Coronary artery disease | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Cardiac failure congestive | 2/89 (2.2%) | 1/55 (1.8%) | 0/80 (0%) | |||
| Eye disorders | ||||||
| Diabetic retinopathy | 1/89 (1.1%) | 0/55 (0%) | 0/80 (0%) | |||
| Retinal vein occlusion | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Visual acuity reduced | 0/89 (0%) | 1/55 (1.8%) | 0/80 (0%) | |||
| Vitreous haemorrhage | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Gastrointestinal disorders | ||||||
| Ascites | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Gastrointestinal haemorrhage | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Vomiting | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| General disorders | ||||||
| Asthenia | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Death | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Hepatobiliary disorders | ||||||
| Hepatic cirrhosis | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Infections and infestations | ||||||
| Bronchitis | 0/89 (0%) | 1/55 (1.8%) | 0/80 (0%) | |||
| Cellulitis | 2/89 (2.2%) | 0/55 (0%) | 0/80 (0%) | |||
| Gangrene | 1/89 (1.1%) | 1/55 (1.8%) | 0/80 (0%) | |||
| Osteomyelitis | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Pneumonia | 0/89 (0%) | 2/55 (3.6%) | 0/80 (0%) | |||
| Localised infection | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fracture displacement | 0/89 (0%) | 1/55 (1.8%) | 0/80 (0%) | |||
| Multiple injuries | 0/89 (0%) | 1/55 (1.8%) | 0/80 (0%) | |||
| Procedural complication | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Road traffic accident | 0/89 (0%) | 1/55 (1.8%) | 0/80 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Diabetes mellitus | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Hyperkalaemia | 1/89 (1.1%) | 0/55 (0%) | 0/80 (0%) | |||
| Hypoglycaemia | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Neuropathic arthropathy | 0/89 (0%) | 1/55 (1.8%) | 0/80 (0%) | |||
| Osteoarthritis | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Hepatocellular carcinoma | 0/89 (0%) | 1/55 (1.8%) | 0/80 (0%) | |||
| Metastases to lung | 0/89 (0%) | 1/55 (1.8%) | 0/80 (0%) | |||
| Nervous system disorders | ||||||
| Central nervous system lesion | 0/89 (0%) | 1/55 (1.8%) | 0/80 (0%) | |||
| Hemiplegic migraine | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Syncope | 1/89 (1.1%) | 0/55 (0%) | 0/80 (0%) | |||
| Psychiatric disorders | ||||||
| Mental status changes | 1/89 (1.1%) | 0/55 (0%) | 0/80 (0%) | |||
| Renal and urinary disorders | ||||||
| Acute kidney injury | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Chronic kidney disease | 1/89 (1.1%) | 0/55 (0%) | 0/80 (0%) | |||
| Nephropathy | 1/89 (1.1%) | 0/55 (0%) | 0/80 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute respiratory failure | 1/89 (1.1%) | 0/55 (0%) | 0/80 (0%) | |||
| Dyspnoea | 1/89 (1.1%) | 0/55 (0%) | 0/80 (0%) | |||
| Pleural effusion | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Vascular disorders | ||||||
| Hypertension | 0/89 (0%) | 1/55 (1.8%) | 0/80 (0%) | |||
| Hypertensive crisis | 0/89 (0%) | 0/55 (0%) | 1/80 (1.3%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Arm A: 0.3 mg Ranibizumab | Arm B: 1.5 mg Faricimab | Arm C: 6 mg Faricimab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 48/89 (53.9%) | 31/55 (56.4%) | 45/80 (56.3%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 9/89 (10.1%) | 1/55 (1.8%) | 5/80 (6.3%) | |||
| Eye disorders | ||||||
| Conjunctival haemorrhage | 7/89 (7.9%) | 2/55 (3.6%) | 8/80 (10%) | |||
| Diabetic retinal oedema | 4/89 (4.5%) | 4/55 (7.3%) | 5/80 (6.3%) | |||
| Dry eye | 2/89 (2.2%) | 0/55 (0%) | 4/80 (5%) | |||
| Eye pain | 3/89 (3.4%) | 3/55 (5.5%) | 2/80 (2.5%) | |||
| Retinal exudates | 1/89 (1.1%) | 4/55 (7.3%) | 3/80 (3.8%) | |||
| Vision blurred | 2/89 (2.2%) | 3/55 (5.5%) | 2/80 (2.5%) | |||
| Vitreous detachment | 3/89 (3.4%) | 3/55 (5.5%) | 2/80 (2.5%) | |||
| Cataract | 2/89 (2.2%) | 0/55 (0%) | 3/80 (3.8%) | |||
| Eye pruritus | 3/89 (3.4%) | 1/55 (1.8%) | 1/80 (1.3%) | |||
| Eyelid oedema | 0/89 (0%) | 2/55 (3.6%) | 0/80 (0%) | |||
| Lacrimation increased | 3/89 (3.4%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Cataract subcapsular | 0/89 (0%) | 2/55 (3.6%) | 0/80 (0%) | |||
| Vitreous haemorrhage | 3/89 (3.4%) | 0/55 (0%) | 0/80 (0%) | |||
| Vitreous floaters | 2/89 (2.2%) | 2/55 (3.6%) | 2/80 (2.5%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 1/89 (1.1%) | 2/55 (3.6%) | 4/80 (5%) | |||
| Dyspepsia | 1/89 (1.1%) | 2/55 (3.6%) | 1/80 (1.3%) | |||
| Nausea | 2/89 (2.2%) | 2/55 (3.6%) | 3/80 (3.8%) | |||
| Vomiting | 3/89 (3.4%) | 0/55 (0%) | 2/80 (2.5%) | |||
| General disorders | ||||||
| Oedema peripheral | 3/89 (3.4%) | 2/55 (3.6%) | 4/80 (5%) | |||
| Infections and infestations | ||||||
| Bronchitis | 3/89 (3.4%) | 3/55 (5.5%) | 1/80 (1.3%) | |||
| Gastroenteritis viral | 0/89 (0%) | 3/55 (5.5%) | 2/80 (2.5%) | |||
| Nasopharyngitis | 3/89 (3.4%) | 3/55 (5.5%) | 5/80 (6.3%) | |||
| Upper respiratory tract infection | 1/89 (1.1%) | 0/55 (0%) | 6/80 (7.5%) | |||
| Urinary tract infection | 6/89 (6.7%) | 4/55 (7.3%) | 1/80 (1.3%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fall | 2/89 (2.2%) | 3/55 (5.5%) | 2/80 (2.5%) | |||
| Investigations | ||||||
| Blood creatine phosphokinase increased | 3/89 (3.4%) | 0/55 (0%) | 0/80 (0%) | |||
| Blood pressure increased | 3/89 (3.4%) | 0/55 (0%) | 0/80 (0%) | |||
| Blood triglycerides increased | 1/89 (1.1%) | 0/55 (0%) | 3/80 (3.8%) | |||
| Red blood cell sedimentation rate increased | 2/89 (2.2%) | 1/55 (1.8%) | 3/80 (3.8%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypercholesterolaemia | 2/89 (2.2%) | 2/55 (3.6%) | 0/80 (0%) | |||
| Hyperlipidaemia | 3/89 (3.4%) | 0/55 (0%) | 1/80 (1.3%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 3/89 (3.4%) | 3/55 (5.5%) | 2/80 (2.5%) | |||
| Back pain | 1/89 (1.1%) | 2/55 (3.6%) | 2/80 (2.5%) | |||
| Pain in extremity | 0/89 (0%) | 1/55 (1.8%) | 3/80 (3.8%) | |||
| Nervous system disorders | ||||||
| Headache | 2/89 (2.2%) | 2/55 (3.6%) | 2/80 (2.5%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 1/89 (1.1%) | 2/55 (3.6%) | 1/80 (1.3%) | |||
| Vascular disorders | ||||||
| Hypertension | 7/89 (7.9%) | 5/55 (9.1%) | 6/80 (7.5%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-La Roche |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02699450
Other Study ID Numbers:
- BP30099
- RG7716
First Posted:
Mar 4, 2016
Last Update Posted:
Sep 25, 2020
Last Verified:
Aug 1, 2020