Neovascularization, ChoroidalPhase 2STAIRWAYNCT03038880
Study to Evaluate Faricimab (RO6867461; RG7716) for Extended Durability in the Treatment of Neovascular Age Related Macular Degeneration
A Phase 2 study testing Faricimab and Ranibizumab in people with Neovascularization, Choroidal and Macular Degeneration, Age-Related, run by Hoffmann-La Roche at 25 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Neovascularization, Choroidal, Macular Degeneration, Age-Related
- What is being tested?
- Faricimab and Ranibizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 25 sitesUnited States
- Study dates
- 27 Jan 2017to 29 Mar 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
Retina Res Institute of Texas
Abilene, Texas, 79606
Eye Associates of New Mexico
Albuquerque, New Mexico, 87109
Texas Retina Associates
Arlington, Texas, 76012
Southeast Retina Center
Augusta, Georgia, 30909
Retina Research Center
Austin, Texas, 78750
California Retina Consultants
Bakersfield, California, 93309
The Retina Care Center
Baltimore, Maryland, 21209
Retinal Diagnostic Center
Campbell, California, 95008
Retina Consultants of Southern Colorado PC; Clinical Research Department
Colorado Springs, Colorado, 80909-1183
Rand Eye
Deerfield Beach, Florida, 33064
Oregon Retina, LLP
Eugene, Oregon, 97401
Charles Retina Institute
Germantown, Tennessee, 38138
Vitreoretinal Consultants
Great Neck, New York, 11021
Midwest Eye Institute
Indianapolis, Indiana, 46290
Florida Eye Associates
Melbourne, Florida, 32901
Vitreo Retinal Surgery
Minneapolis, Minnesota, 55435
Retinal Consultants of Arizona
Phoenix, Arizona, 85053
Retina Northwest
Portland, Oregon, 97221
Sierra Eye Associates
Reno, Nevada, 89502
Retina Associates of Utah
Salt Lake City, Utah, 84107
Retina Vitreous Assoc of FL
St. Petersburg, Florida, 33711
Southern Vitreoretinal Assoc
Tallahassee, Florida, 32308
Retina Associates Southwest PC
Tucson, Arizona, 85704
Wolfe Eye Clinic
West Des Moines, Iowa, 50266
Strategic Clinical Research Group, LLC
Willow Park, Texas, 76087
About this study
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
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.
- Being tested
- Faricimab, Ranibizumab, Sham Procedure
- Medical subject headings
- Choroidal Neovascularization, Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FaricimabDrug
Also called RO6867461, RG7716
Faricimab was administered via IVT injections as specified during the treatment period.
RanibizumabDrug
Also called Lucentis®
Ranibizumab was administered via IVT injections as specified during the treatment period.
Sham ProcedureDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 6 mg Faricimab Q12W | Experimental | 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). Receives: Drug: Faricimab; Drug: Sham Procedure |
| 6 mg Faricimab Q16W | Experimental | 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. Receives: Drug: Faricimab; Drug: Sham Procedure |
| 0.5 mg Ranibizumab Q4W | Active comparator | 0.5 mg of ranibizumab was administered by IVT injection once every 4 weeks (Q4W) for 48 weeks (13 injections). Receives: Drug: Ranibizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 40
Secondary outcomes (18)
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.
Measured: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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.
Measured: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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.
Measured: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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.
Measured: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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.
Measured: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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.
Measured: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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.
Measured: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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.
Measured: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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.
Measured: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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.
Measured: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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.
Measured: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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.
Measured: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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.
Measured: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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).
Measured: Baseline, Week 40, Week 52
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).
Measured: Baseline, Week 40, Week 52
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).
Measured: Baseline, Week 40, Week 52
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).
Measured: Predose at Baseline (Day 1), Weeks 16, 24, 28, 44, and 52
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.
Measured: From Baseline until 28 days after the last dose of study drug (up to 52 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2017 (estimated)
- Study start27 Jan 2017
- Primary completion11 Jan 2018
- Study completion29 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neovascularization, ChoroidalStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03038880
- Sponsor's protocol ID
- CR39521
- Acronym
- STAIRWAY
- Status last verified
- Dec 2020
- First submitted
- 31 Jan 2017
- Last updated
- 5 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 32729897
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03038880
- Acronym / sponsor ID
- STAIRWAY / CR39521
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 27 Jan 2017 (actual)
- Primary completion
- 11 Jan 2018 (actual)
- Study completion
- 29 Mar 2018 (actual)
- First posted
- 1 Feb 2017 (estimated)
- Results
- Posted 5 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 6 mg Faricimab Q12W | Experimental | Drug: Faricimab, Drug: Sham Procedure6 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 Q16W | Experimental | Drug: Faricimab, Drug: Sham Procedure6 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 Ranibizumab Q4W | Active comparator | Drug: Ranibizumab0.5 mg of ranibizumab was administered by IVT injection once every 4 weeks (Q4W) for 48 weeks (13 injections). |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FaricimabAlso: RO6867461, RG7716Faricimab was administered via IVT injections as specified during the treatment period. | Drug | 6 mg Faricimab Q12W, 6 mg Faricimab Q16W |
| RanibizumabAlso: Lucentis®Ranibizumab was administered via IVT injections as specified during the treatment period. | Drug | 0.5 mg Ranibizumab Q4W |
| Sham ProcedureThe 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. | Drug | 6 mg Faricimab Q12W, 6 mg Faricimab Q16W |
Primary outcome
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 40, Using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA Charts
Time frame: Baseline, Week 40
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.
18 secondary outcomes
Mean Change From Baseline in BCVA at Specified Timepoints, Using the ETDRS BCVA Charts
Time frame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Number and Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters From Baseline in BCVA at Specified Timepoints
Time frame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Percentage of Participants Gaining ≥15 Letters From Baseline in BCVA at Specified Timepoints
Time frame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Number and Percentage of Participants Not Losing ≥15, ≥10, ≥5, or ≥0 Letters From Baseline in BCVA at Specified Timepoints
Time frame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Percentage of Participants Not Losing ≥15 Letters From Baseline in BCVA at Specified Timepoints
Time frame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Specified Timepoints
Time frame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Specified Timepoints
Time frame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Mean Change From Baseline in Central Foveal Thickness (CFT) at Specified Timepoints
Time frame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Mean Change From Baseline in Central Subfield Thickness (CST) at Specified Timepoints
Time frame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Percentage of Participants With No Intraretinal Fluid at Specified Timepoints
Time frame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Percentage of Participants With No Subretinal Fluid at Specified Timepoints
Time frame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Percentage of Participants With No Cysts at Specified Timepoints
Time frame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Percentage of Participants With No Pigment Epithelial Detachment at Specified Timepoints
Time frame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Mean Baseline Value and Mean Change From Baseline of Total Area of Choroidal Neovascularization (CNV) at Week 40 and Week 52
Time frame: Baseline, Week 40, Week 52
Mean Baseline Value and Mean Change From Baseline of Total Area of CNV Component at Week 40 and Week 52
Time frame: Baseline, Week 40, Week 52
Mean Baseline Value and Mean Change From Baseline of Total Area of Leakage at Week 40 and Week 52
Time frame: Baseline, Week 40, Week 52
Change From Baseline in the Number of Participants With Anti-Drug Antibodies (ADA) to Faricimab at Anytime Post-Baseline
Time frame: Predose at Baseline (Day 1), Weeks 16, 24, 28, 44, and 52
Safety Summary: Number and Percentage of Participants With at Least One Adverse Event
Time frame: From Baseline until 28 days after the last dose of study drug (up to 52 weeks)
Results and safety
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Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32729897Khanani 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Faricimab and Ranibizumab in people with Neovascularization, Choroidal and Macular Degeneration, Age-Related, run by Hoffmann-La Roche at 25 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 40, Using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA Charts (time frame: Baseline, Week 40). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03038880, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2021.