Back to resultsStudy to Evaluate Faricimab (RO6867461; RG7716) for Extended Durability in the Treatment of Neovascular Age Related Macular Degeneration (STAIRWAY)
Primary Purpose
Neovascularization, Choroidal, Macular Degeneration, Age-Related
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Faricimab
Ranibizumab
Sham Procedure
Sponsored by
About this trial
This is an interventional treatment trial for Neovascularization, Choroidal
Eligibility Criteria
Inclusion Criteria
- Treatment-naive CNV secondary to AMD (nAMD)
- Subfoveal or juxtafoveal CNV with a subfoveal component related to the CNV activity by fundus fluorescein angiography (FFA) or spectral-domain optical coherence tomography (SD-OCT; as evidenced by subretinal fluid, subretinal hyperreflective material, evidence of leakage, or hemorrhage)
- CNV lesion of all types with: total lesion size (including blood, atrophy, fibrosis, and neovascularization) of 6 disc areas or less by FFA; and CNV component area of at least 50% of total lesion size by FFA; and active CNV confirmed by FFA (evidence of leakage); and CNV exudation confirmed by SD-OCT (presence of fluid)
- BCVA letter score of 73 to 24 letters (inclusive) on ETDRS-like charts (20/40-20/320 Snellen equivalent) on day 1
- Clear ocular media and adequate pupillary dilatation to allow acquisition of good-quality retinal images to confirm diagnosis
Exclusion Criteria:
- CNV due to causes other than AMD, such as ocular histoplasmosis, trauma, pathological myopia, angioid streaks, choroidal rupture, or uveitis
- Central serous chorioretinopathy at screening
- Retinal pigment epithelial tear involving the macula
- On FFA: subretinal hemorrhage, fibrosis, or atrophy of more than (>)50% of the total lesion area and/or that involves the fovea
- Any prior or concomitant treatment for CNV including (but not restricted to) IVT treatment (steroids, anti-VEGF, tissue plasminogen activator, ocriplasmin, C3F8 gas, air), periocular pharmacological intervention, argon laser photocoagulation, verteporfin photodynamic therapy, diode laser, transpupillary thermotherapy, or surgical intervention
- Cataract surgery within 3 months of baseline assessments
- Any other intraocular surgery (pars plana vitrectomy, glaucoma surgery, corneal transplant, radiotherapy)
- Prior IVT treatment (including anti-VEGF medication) except for management of cataract complication with steroid IVT treatment
- Prior periocular pharmacological intervention for other retinal diseases
- Any concurrent intraocular condition in the study eye (eg, amblyopia, aphakia, retinal detachment, cataract, diabetic retinopathy or maculopathy, or epiretinal membrane with traction) that, in the opinion of the investigator, could either reduce the potential for visual improvement or require medical or surgical intervention during the course of the study
- Active intraocular inflammation (grade trace or above) in the study eye on day 1 (before randomization)
- Current vitreous hemorrhage in the study eye
- Uncontrolled glaucoma (eg, progressive loss of visual fields or defined as IOP ≥25 mm Hg despite treatment with antiglaucoma medication) in the study eye
- Spherical equivalent of refractive error demonstrating more than 8 diopters of myopia in the study eye
- History of idiopathic or autoimmune-associated uveitis in either eye
- Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye on day 1 (before randomization)
- Any major illness or major surgical procedure within 1 month before screening
- Uncontrolled blood pressure (defined as systolic >180 mm Hg and/or diastolic >100 mm Hg while participant at rest). If a participant's initial reading exceeded these values, a second reading was taken later on the same day, or on another day during the screening period. If the participant's blood pressure was controlled by antihypertensive medication, the participant was taking the same medication continuously for at least 30 days before day 1
- Stroke or myocardial infarction within 3 months before day 1
- History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory findings giving reasonable suspicion of a condition that contraindicated the use of the investigational drug or that might affect interpretation of the results of the study or renders the participant at high risk for treatment complications in the opinion of the investigator
- Pregnant or breastfeeding, or intended to become pregnant during the study
- Known hypersensitivity to ranibizumab, fluorescein, any ingredients of the formulation used, dilating eye drops, or any of the anesthetic and antimicrobial drops used
- Treatment with investigational therapy within 3 months before initiation of study treatment
Sites / Locations
- Retinal Consultants of Arizona
- Retina Associates Southwest PC
- California Retina Consultants
- Retinal Diagnostic Center
- Retina Consultants of Southern Colorado PC; Clinical Research Department
- Rand Eye
- Florida Eye Associates
- Retina Vitreous Assoc of FL
- Southern Vitreoretinal Assoc
- Southeast Retina Center
- Midwest Eye Institute
- Wolfe Eye Clinic
- The Retina Care Center
- Vitreo Retinal Surgery
- Sierra Eye Associates
- Eye Associates of New Mexico
- Vitreoretinal Consultants
- Oregon Retina, LLP
- Retina Northwest
- Charles Retina Institute
- Retina Res Institute of Texas
- Texas Retina Associates
- Retina Research Center
- Strategic Clinical Research Group, LLC
- Retina Associates of Utah
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
6 mg Faricimab Q12W
6 mg Faricimab Q16W
0.5 mg Ranibizumab Q4W
Arm Description
6 mg faricimab was given by intravitreal (IVT) injection once every 4 weeks (Q4W) up to Week 12 (4 injections), followed by 6 mg faricimab IVT injection once every 12 weeks (Q12W) from Week 24 up to Week 48 (injections at Weeks 24, 36, and 48; 3 injections).
6 mg faricimab was administered by IVT injection once every 4 weeks (Q4W) up to Week 12 (4 injections), followed by no doses up to Week 24 when a protocol-defined assessment of disease activity was performed. Participants with disease activity at Week 24 initiated 6 mg faricimab IVT Q12W dosing, and participants without disease activity at Week 24 initiated 6 mg faricimab IVT once every 16 weeks (Q16W) dosing for the remainder of the study.
0.5 mg of ranibizumab was administered by IVT injection once every 4 weeks (Q4W) for 48 weeks (13 injections).
Outcomes
Primary Outcome Measures
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 40, Using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA Charts
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The analysis was performed using a Mixed Model for Repeated Measurement (MMRM) model, which included an unstructured covariance and the categorical covariates of treatment group, visit, and visit by treatment group interaction and the continuous covariate of baseline BCVA.
Secondary Outcome Measures
Mean Change From Baseline in BCVA at Specified Timepoints, Using the ETDRS BCVA Charts
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The analysis was performed using a Mixed Model for Repeated Measurement (MMRM) model, which included an unstructured covariance and the categorical covariates of treatment group, visit, and visit by treatment group interaction and the continuous covariate of baseline BCVA.
Number and Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters From Baseline in BCVA at Specified Timepoints
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis was performed on observed data.
Percentage of Participants Gaining ≥15 Letters From Baseline in BCVA at Specified Timepoints
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Number and Percentage of Participants Not Losing ≥15, ≥10, ≥5, or ≥0 Letters From Baseline in BCVA at Specified Timepoints
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a loss in BCVA letter score from baseline indicates worsening in visual acuity. This analysis was performed on observed data.
Percentage of Participants Not Losing ≥15 Letters From Baseline in BCVA at Specified Timepoints
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Specified Timepoints
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Specified Timepoints
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Mean Change From Baseline in Central Foveal Thickness (CFT) at Specified Timepoints
Central foveal thickness (CFT) was 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, and it was measured using spectral domain optical coherence tomography (SD-OCT). The analysis was performed using a Mixed Model for Repeated Measurement (MMRM) model, which included an unstructured covariance and the categorical covariates of treatment group, visit, and visit by treatment group interaction and the continuous covariate of baseline CFT.
Mean Change From Baseline in Central Subfield Thickness (CST) at Specified Timepoints
Central subfield thickness (CST) was defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield, and it was measured using spectral domain optical coherence tomography (SD-OCT). The analysis was performed using a Mixed Model for Repeated Measurement (MMRM) model, which included an unstructured covariance and the categorical covariates of treatment group, visit, and visit by treatment group interaction and the continuous covariate of baseline CST.
Percentage of Participants With No Intraretinal Fluid at Specified Timepoints
The absence of intraretinal fluid, subretinal fluid, cysts, or pigment epithelial detachment, as per the study's dry retina definition, were evaluated as individual dry retina outcomes. Intraretinal fluid was defined as the presence of fluid within the retina. All parameters were measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Percentage of Participants With No Subretinal Fluid at Specified Timepoints
The absence of intraretinal fluid, subretinal fluid, cysts, or pigment epithelial detachment, as per the study's dry retina definition, were evaluated as individual dry retina outcomes. Subretinal fluid was defined as the presence of fluid between the retina and the retinal pigment epithelium. All parameters were measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Percentage of Participants With No Cysts at Specified Timepoints
The absence of intraretinal fluid, subretinal fluid, cysts, or pigment epithelial detachment, as per the study's dry retina definition, were evaluated as individual dry retina outcomes. Cysts were defined as the presence of cystoid space (fluid) in the retina. All parameters were measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Percentage of Participants With No Pigment Epithelial Detachment at Specified Timepoints
The absence of intraretinal fluid, subretinal fluid, cysts, or pigment epithelial detachment, as per the study's dry retina definition, were evaluated as individual dry retina outcomes. Pigment epithelial detachment was defined as the presence of a detachment of the pigment epithelium from the Bruch's membrane. All parameters were measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Mean Baseline Value and Mean Change From Baseline of Total Area of Choroidal Neovascularization (CNV) at Week 40 and Week 52
The total area of choroidal neovascularization (CNV) was evaluated by a central reading center using fundus fluorescein angiography (FFA).
Mean Baseline Value and Mean Change From Baseline of Total Area of CNV Component at Week 40 and Week 52
The total area of choroidal neovascularization (CNV) component (i.e., total area of CNV membrane) was evaluated by a central reading center using fundus fluorescein angiography (FFA).
Mean Baseline Value and Mean Change From Baseline of Total Area of Leakage at Week 40 and Week 52
The total area of leakage was evaluated by a central reading center using fundus fluorescein angiography (FFA).
Change From Baseline in the Number of Participants With Anti-Drug Antibodies (ADA) to Faricimab at Anytime Post-Baseline
Blood samples were obtained for measurement of anti-drug antibodies (ADAs) to faricimab by a validated enzyme-linked immunosorbent assay (ELISA).
Safety Summary: Number and Percentage of Participants With at Least One Adverse Event
This safety summary reports the number and percentage of participants who experienced at least one adverse event (AE) during the study. The investigator independently assessed the seriousness and severity for each AE. Severity was graded according to the following grading scale: Mild = Discomfort noticed, but no disruption of normal daily activity; Moderate = Discomfort sufficient to reduce or affect normal daily activity; Severe = Incapacitating with inability to work or to perform normal daily activity. Severity and seriousness are not synonymous; regardless of severity, some AEs may have also met seriousness criteria.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03038880
Brief Title
Study to Evaluate Faricimab (RO6867461; RG7716) for Extended Durability in the Treatment of Neovascular Age Related Macular Degeneration
Acronym
STAIRWAY
Official Title
STAIRWAY: Simultaneous Blockade of Angiopoietin-2 and VEGF-A With the Bispecific Antibody RO6867461 (RG7716) for Extended Durability in the Treatment of Neovascular Age-Related Macular Degeneration
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
January 27, 2017 (Actual)
Primary Completion Date
January 11, 2018 (Actual)
Study Completion Date
March 29, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This was a Phase II, multicenter, randomized, active comparator-controlled, 52-week study to investigate the efficacy, safety and pharmacokinetics of faricimab (RO6867461; RG7716) administered with extended dosing regimens in treatment-naive participants with neovascular age related macular degeneration (nAMD). Only one eye was chosen as the study eye.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neovascularization, Choroidal, Macular Degeneration, Age-Related
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
76 (Actual)
8. Arms, Groups, and Interventions
Arm Title
6 mg Faricimab Q12W
Arm Type
Experimental
Arm Description
6 mg faricimab was given by intravitreal (IVT) injection once every 4 weeks (Q4W) up to Week 12 (4 injections), followed by 6 mg faricimab IVT injection once every 12 weeks (Q12W) from Week 24 up to Week 48 (injections at Weeks 24, 36, and 48; 3 injections).
Arm Title
6 mg Faricimab Q16W
Arm Type
Experimental
Arm Description
6 mg faricimab was administered by IVT injection once every 4 weeks (Q4W) up to Week 12 (4 injections), followed by no doses up to Week 24 when a protocol-defined assessment of disease activity was performed. Participants with disease activity at Week 24 initiated 6 mg faricimab IVT Q12W dosing, and participants without disease activity at Week 24 initiated 6 mg faricimab IVT once every 16 weeks (Q16W) dosing for the remainder of the study.
Arm Title
0.5 mg Ranibizumab Q4W
Arm Type
Active Comparator
Arm Description
0.5 mg of ranibizumab was administered by IVT injection once every 4 weeks (Q4W) for 48 weeks (13 injections).
Intervention Type
Drug
Intervention Name(s)
Faricimab
Other Intervention Name(s)
RO6867461, RG7716
Intervention Description
Faricimab was administered via IVT injections as specified during the treatment period.
Intervention Type
Drug
Intervention Name(s)
Ranibizumab
Other Intervention Name(s)
Lucentis®
Intervention Description
Ranibizumab was administered via IVT injections as specified during the treatment period.
Intervention Type
Drug
Intervention Name(s)
Sham Procedure
Intervention Description
The sham was a procedure that mimicked an IVT injection and involved the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. It was administered to participants in the faricimab treatments arms at applicable visits to maintain masking among treatment arms.
Primary Outcome Measure Information:
Title
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 40, Using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA Charts
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The analysis was performed using a Mixed Model for Repeated Measurement (MMRM) model, which included an unstructured covariance and the categorical covariates of treatment group, visit, and visit by treatment group interaction and the continuous covariate of baseline BCVA.
Time Frame
Baseline, Week 40
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in BCVA at Specified Timepoints, Using the ETDRS BCVA Charts
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The analysis was performed using a Mixed Model for Repeated Measurement (MMRM) model, which included an unstructured covariance and the categorical covariates of treatment group, visit, and visit by treatment group interaction and the continuous covariate of baseline BCVA.
Time Frame
Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Number and Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters From Baseline in BCVA at Specified Timepoints
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis was performed on observed data.
Time Frame
Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Percentage of Participants Gaining ≥15 Letters From Baseline in BCVA at Specified Timepoints
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Time Frame
Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Number and Percentage of Participants Not Losing ≥15, ≥10, ≥5, or ≥0 Letters From Baseline in BCVA at Specified Timepoints
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a loss in BCVA letter score from baseline indicates worsening in visual acuity. This analysis was performed on observed data.
Time Frame
Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Percentage of Participants Not Losing ≥15 Letters From Baseline in BCVA at Specified Timepoints
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Time Frame
Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Specified Timepoints
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Time Frame
Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Specified Timepoints
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. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Time Frame
Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Mean Change From Baseline in Central Foveal Thickness (CFT) at Specified Timepoints
Description
Central foveal thickness (CFT) was 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, and it was measured using spectral domain optical coherence tomography (SD-OCT). The analysis was performed using a Mixed Model for Repeated Measurement (MMRM) model, which included an unstructured covariance and the categorical covariates of treatment group, visit, and visit by treatment group interaction and the continuous covariate of baseline CFT.
Time Frame
Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Mean Change From Baseline in Central Subfield Thickness (CST) at Specified Timepoints
Description
Central subfield thickness (CST) was defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield, and it was measured using spectral domain optical coherence tomography (SD-OCT). The analysis was performed using a Mixed Model for Repeated Measurement (MMRM) model, which included an unstructured covariance and the categorical covariates of treatment group, visit, and visit by treatment group interaction and the continuous covariate of baseline CST.
Time Frame
Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Percentage of Participants With No Intraretinal Fluid at Specified Timepoints
Description
The absence of intraretinal fluid, subretinal fluid, cysts, or pigment epithelial detachment, as per the study's dry retina definition, were evaluated as individual dry retina outcomes. Intraretinal fluid was defined as the presence of fluid within the retina. All parameters were measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Time Frame
Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Percentage of Participants With No Subretinal Fluid at Specified Timepoints
Description
The absence of intraretinal fluid, subretinal fluid, cysts, or pigment epithelial detachment, as per the study's dry retina definition, were evaluated as individual dry retina outcomes. Subretinal fluid was defined as the presence of fluid between the retina and the retinal pigment epithelium. All parameters were measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Time Frame
Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Percentage of Participants With No Cysts at Specified Timepoints
Description
The absence of intraretinal fluid, subretinal fluid, cysts, or pigment epithelial detachment, as per the study's dry retina definition, were evaluated as individual dry retina outcomes. Cysts were defined as the presence of cystoid space (fluid) in the retina. All parameters were measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Time Frame
Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Percentage of Participants With No Pigment Epithelial Detachment at Specified Timepoints
Description
The absence of intraretinal fluid, subretinal fluid, cysts, or pigment epithelial detachment, as per the study's dry retina definition, were evaluated as individual dry retina outcomes. Pigment epithelial detachment was defined as the presence of a detachment of the pigment epithelium from the Bruch's membrane. All parameters were measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis was performed on observed data. The 80% confidence intervals were calculated using the Wald method.
Time Frame
Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Mean Baseline Value and Mean Change From Baseline of Total Area of Choroidal Neovascularization (CNV) at Week 40 and Week 52
Description
The total area of choroidal neovascularization (CNV) was evaluated by a central reading center using fundus fluorescein angiography (FFA).
Time Frame
Baseline, Week 40, Week 52
Title
Mean Baseline Value and Mean Change From Baseline of Total Area of CNV Component at Week 40 and Week 52
Description
The total area of choroidal neovascularization (CNV) component (i.e., total area of CNV membrane) was evaluated by a central reading center using fundus fluorescein angiography (FFA).
Time Frame
Baseline, Week 40, Week 52
Title
Mean Baseline Value and Mean Change From Baseline of Total Area of Leakage at Week 40 and Week 52
Description
The total area of leakage was evaluated by a central reading center using fundus fluorescein angiography (FFA).
Time Frame
Baseline, Week 40, Week 52
Title
Change From Baseline in the Number of Participants With Anti-Drug Antibodies (ADA) to Faricimab at Anytime Post-Baseline
Description
Blood samples were obtained for measurement of anti-drug antibodies (ADAs) to faricimab by a validated enzyme-linked immunosorbent assay (ELISA).
Time Frame
Predose at Baseline (Day 1), Weeks 16, 24, 28, 44, and 52
Title
Safety Summary: Number and Percentage of Participants With at Least One Adverse Event
Description
This safety summary reports the number and percentage of participants who experienced at least one adverse event (AE) during the study. The investigator independently assessed the seriousness and severity for each AE. Severity was graded according to the following grading scale: Mild = Discomfort noticed, but no disruption of normal daily activity; Moderate = Discomfort sufficient to reduce or affect normal daily activity; Severe = Incapacitating with inability to work or to perform normal daily activity. Severity and seriousness are not synonymous; regardless of severity, some AEs may have also met seriousness criteria.
Time Frame
From Baseline until 28 days after the last dose of study drug (up to 52 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Treatment-naive CNV secondary to AMD (nAMD)
Subfoveal or juxtafoveal CNV with a subfoveal component related to the CNV activity by fundus fluorescein angiography (FFA) or spectral-domain optical coherence tomography (SD-OCT; as evidenced by subretinal fluid, subretinal hyperreflective material, evidence of leakage, or hemorrhage)
CNV lesion of all types with: total lesion size (including blood, atrophy, fibrosis, and neovascularization) of 6 disc areas or less by FFA; and CNV component area of at least 50% of total lesion size by FFA; and active CNV confirmed by FFA (evidence of leakage); and CNV exudation confirmed by SD-OCT (presence of fluid)
BCVA letter score of 73 to 24 letters (inclusive) on ETDRS-like charts (20/40-20/320 Snellen equivalent) on day 1
Clear ocular media and adequate pupillary dilatation to allow acquisition of good-quality retinal images to confirm diagnosis
Exclusion Criteria:
CNV due to causes other than AMD, such as ocular histoplasmosis, trauma, pathological myopia, angioid streaks, choroidal rupture, or uveitis
Central serous chorioretinopathy at screening
Retinal pigment epithelial tear involving the macula
On FFA: subretinal hemorrhage, fibrosis, or atrophy of more than (>)50% of the total lesion area and/or that involves the fovea
Any prior or concomitant treatment for CNV including (but not restricted to) IVT treatment (steroids, anti-VEGF, tissue plasminogen activator, ocriplasmin, C3F8 gas, air), periocular pharmacological intervention, argon laser photocoagulation, verteporfin photodynamic therapy, diode laser, transpupillary thermotherapy, or surgical intervention
Cataract surgery within 3 months of baseline assessments
Any other intraocular surgery (pars plana vitrectomy, glaucoma surgery, corneal transplant, radiotherapy)
Prior IVT treatment (including anti-VEGF medication) except for management of cataract complication with steroid IVT treatment
Prior periocular pharmacological intervention for other retinal diseases
Any concurrent intraocular condition in the study eye (eg, amblyopia, aphakia, retinal detachment, cataract, diabetic retinopathy or maculopathy, or epiretinal membrane with traction) that, in the opinion of the investigator, could either reduce the potential for visual improvement or require medical or surgical intervention during the course of the study
Active intraocular inflammation (grade trace or above) in the study eye on day 1 (before randomization)
Current vitreous hemorrhage in the study eye
Uncontrolled glaucoma (eg, progressive loss of visual fields or defined as IOP ≥25 mm Hg despite treatment with antiglaucoma medication) in the study eye
Spherical equivalent of refractive error demonstrating more than 8 diopters of myopia in the study eye
History of idiopathic or autoimmune-associated uveitis in either eye
Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye on day 1 (before randomization)
Any major illness or major surgical procedure within 1 month before screening
Uncontrolled blood pressure (defined as systolic >180 mm Hg and/or diastolic >100 mm Hg while participant at rest). If a participant's initial reading exceeded these values, a second reading was taken later on the same day, or on another day during the screening period. If the participant's blood pressure was controlled by antihypertensive medication, the participant was taking the same medication continuously for at least 30 days before day 1
Stroke or myocardial infarction within 3 months before day 1
History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory findings giving reasonable suspicion of a condition that contraindicated the use of the investigational drug or that might affect interpretation of the results of the study or renders the participant at high risk for treatment complications in the opinion of the investigator
Pregnant or breastfeeding, or intended to become pregnant during the study
Known hypersensitivity to ranibizumab, fluorescein, any ingredients of the formulation used, dilating eye drops, or any of the anesthetic and antimicrobial drops used
Treatment with investigational therapy within 3 months before initiation of study treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Retinal Consultants of Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85053
Country
United States
Facility Name
Retina Associates Southwest PC
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
California Retina Consultants
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309
Country
United States
Facility Name
Retinal Diagnostic Center
City
Campbell
State/Province
California
ZIP/Postal Code
95008
Country
United States
Facility Name
Retina Consultants of Southern Colorado PC; Clinical Research Department
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80909-1183
Country
United States
Facility Name
Rand Eye
City
Deerfield Beach
State/Province
Florida
ZIP/Postal Code
33064
Country
United States
Facility Name
Florida Eye Associates
City
Melbourne
State/Province
Florida
ZIP/Postal Code
32901
Country
United States
Facility Name
Retina Vitreous Assoc of FL
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33711
Country
United States
Facility Name
Southern Vitreoretinal Assoc
City
Tallahassee
State/Province
Florida
ZIP/Postal Code
32308
Country
United States
Facility Name
Southeast Retina Center
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30909
Country
United States
Facility Name
Midwest Eye Institute
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46290
Country
United States
Facility Name
Wolfe Eye Clinic
City
West Des Moines
State/Province
Iowa
ZIP/Postal Code
50266
Country
United States
Facility Name
The Retina Care Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21209
Country
United States
Facility Name
Vitreo Retinal Surgery
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55435
Country
United States
Facility Name
Sierra Eye Associates
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
Eye Associates of New Mexico
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87109
Country
United States
Facility Name
Vitreoretinal Consultants
City
Great Neck
State/Province
New York
ZIP/Postal Code
11021
Country
United States
Facility Name
Oregon Retina, LLP
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
Retina Northwest
City
Portland
State/Province
Oregon
ZIP/Postal Code
97221
Country
United States
Facility Name
Charles Retina Institute
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Retina Res Institute of Texas
City
Abilene
State/Province
Texas
ZIP/Postal Code
79606
Country
United States
Facility Name
Texas Retina Associates
City
Arlington
State/Province
Texas
ZIP/Postal Code
76012
Country
United States
Facility Name
Retina Research Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78750
Country
United States
Facility Name
Strategic Clinical Research Group, LLC
City
Willow Park
State/Province
Texas
ZIP/Postal Code
76087
Country
United States
Facility Name
Retina Associates of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
32729897
Citation
Khanani AM, Patel SS, Ferrone PJ, Osborne A, Sahni J, Grzeschik S, Basu K, Ehrlich JS, Haskova Z, Dugel PU. Efficacy of Every Four Monthly and Quarterly Dosing of Faricimab vs Ranibizumab in Neovascular Age-Related Macular Degeneration: The STAIRWAY Phase 2 Randomized Clinical Trial. JAMA Ophthalmol. 2020 Sep 1;138(9):964-972. doi: 10.1001/jamaophthalmol.2020.2699. Erratum In: JAMA Ophthalmol. 2020 Sep 1;138(9):1006.
Results Reference
derived
Learn more about this trial
Study to Evaluate Faricimab (RO6867461; RG7716) for Extended Durability in the Treatment of Neovascular Age Related Macular Degeneration
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