A Study of Faricimab (RO6867461) in Participants With Center-Involving Diabetic Macular Edema
- Registration Number
- NCT02699450
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 229
- Macular edema associated with diabetic retinopathy
- Decreased visual acuity attributable primarily to DME
- Diagnosis of diabetes mellitus
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: 0.3 mg Ranibizumab 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. Arm B: 1.5 mg Faricimab 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. Arm C: 6 mg Faricimab 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 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.
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.
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 ≥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.
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).
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 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 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).
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.
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 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.
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 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.
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.
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.
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 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 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 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.
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.
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.
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.
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.
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 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
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 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).
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.
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 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.
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.
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 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.
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 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 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.
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
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.
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.
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)
Trial Locations
- Locations (59)
United Med Res Inst
🇺🇸Inglewood, California, United States
Ophthalmic Clinical Trials San Diego
🇺🇸Oceanside, California, United States
Southern CA Desert Retina Cons
🇺🇸Palm Desert, California, United States
Retina Consultants, San Diego
🇺🇸Poway, California, United States
Bay Area Retina Associates
🇺🇸Walnut Creek, California, United States
Retina Consultants of Southern
🇺🇸Colorado Springs, Colorado, United States
Retina Vitreous Assoc of FL
🇺🇸Saint Petersburg, Florida, United States
Retina Specialty Institute
🇺🇸Pensacola, Florida, United States
University Retina and Macula Associates, PC
🇺🇸Oak Forest, Illinois, United States
Illinois Retina Associates SC
🇺🇸Oak Park, Illinois, United States
Wolfe Eye Clinic
🇺🇸West Des Moines, Iowa, United States
Vitreo-Retinal Associates
🇺🇸Grand Rapids, Michigan, United States
Retina Associates of Kentucky
🇺🇸Lexington, Kentucky, United States
Vitreoretinal Surgery
🇺🇸Edina, Minnesota, United States
Eye Associates of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Opthalmic Consultants of LI
🇺🇸Lynbrook, New York, United States
Char Eye Ear &Throat Assoc
🇺🇸Charlotte, North Carolina, United States
Oregon Retina, LLP
🇺🇸Eugene, Oregon, United States
W Texas Retina Consultants PA
🇺🇸Abilene, Texas, United States
Retina Specialists
🇺🇸DeSoto, Texas, United States
Univ of Virginia Ophthalmology
🇺🇸Charlottesville, Virginia, United States
Spokane Eye Clinical Research
🇺🇸Spokane, Washington, United States
Retina Associates Southwest PC
🇺🇸Tucson, Arizona, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Palmetto Retina Center
🇺🇸Florence, South Carolina, United States
Retina Center of New Jersey
🇺🇸Bloomfield, New Jersey, United States
Charleston Neuroscience Inst
🇺🇸Ladson, South Carolina, United States
Charles Retina Institute
🇺🇸Germantown, Tennessee, United States
Retina Consultants of Orange County
🇺🇸Fullerton, California, United States
Northern California Retina Vitreous Associates
🇺🇸Mountain View, California, United States
California Retina Consultants
🇺🇸Santa Barbara, California, United States
Rand Eye
🇺🇸Deerfield Beach, Florida, United States
National Ophthalmic Research Institute
🇺🇸Fort Myers, Florida, United States
Florida Eye Associates
🇺🇸Melbourne, Florida, United States
Southern Vitreoretinal Assoc
🇺🇸Tallahassee, Florida, United States
Southeast Retina Center
🇺🇸Augusta, Georgia, United States
Georgia Retina PC
🇺🇸Marietta, Georgia, United States
Univ of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
Paducah Retinal Center
🇺🇸Paducah, Kentucky, United States
Wilmer Eye Institute
🇺🇸Baltimore, Maryland, United States
Capital Region Retina
🇺🇸Albany, New York, United States
Western Carolina Retinal Associate PA
🇺🇸Asheville, North Carolina, United States
Sierra Eye Associates
🇺🇸Reno, Nevada, United States
OSU Eye Physicians & Surgeons
🇺🇸Columbus, Ohio, United States
West Virginia University Eye Institute
🇺🇸Morgantown, West Virginia, United States
Retina Consultants of Western New York
🇺🇸Orchard Park, New York, United States
Retina Consultants of Houston
🇺🇸The Woodlands, Texas, United States
Cleveland Clinic Foundation; Cole Eye Institute
🇺🇸Cleveland, Ohio, United States
Retinal Research Institute, LLC
🇺🇸Phoenix, Arizona, United States
Associated Retina Consultants
🇺🇸Phoenix, Arizona, United States
Arizona Retina and Vitreous Consultants
🇺🇸Phoenix, Arizona, United States
Retinal Consultants Med Group
🇺🇸Sacramento, California, United States
Midwest Eye Institute
🇺🇸Indianapolis, Indiana, United States
Retina Northwest
🇺🇸Portland, Oregon, United States
Tennessee Retina PC.
🇺🇸Nashville, Tennessee, United States
Med Center Ophthalmology Assoc
🇺🇸San Antonio, Texas, United States
Retina Associates of Utah
🇺🇸Salt Lake City, Utah, United States
Austin Retina Associates
🇺🇸Austin, Texas, United States
Retina Consultants of Austin
🇺🇸Austin, Texas, United States