Clinical trial NCT03038880: Study to Evaluate Faricimab (RO6867461; RG7716) for Extended Durability in the Treatment of Neovascular Age Related Macular Degeneration
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neovascularization, Choroidal
Macular Degeneration, Age-Related
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-02-01
Enrollment: 76
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 40, Using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA Charts
timeFrame: Baseline, Week 40
Secondary outcomes:
measure: Mean Change From Baseline in BCVA at Specified Timepoints, Using the ETDRS BCVA Charts
timeFrame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Number and Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters From Baseline in BCVA at Specified Timepoints
timeFrame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Percentage of Participants Gaining ≥15 Letters From Baseline in BCVA at Specified Timepoints
timeFrame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Number and Percentage of Participants Not Losing ≥15, ≥10, ≥5, or ≥0 Letters From Baseline in BCVA at Specified Timepoints
timeFrame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Percentage of Participants Not Losing ≥15 Letters From Baseline in BCVA at Specified Timepoints
timeFrame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Specified Timepoints
timeFrame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Specified Timepoints
timeFrame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Mean Change From Baseline in Central Foveal Thickness (CFT) at Specified Timepoints
timeFrame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Mean Change From Baseline in Central Subfield Thickness (CST) at Specified Timepoints
timeFrame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Percentage of Participants With No Intraretinal Fluid at Specified Timepoints
timeFrame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Percentage of Participants With No Subretinal Fluid at Specified Timepoints
timeFrame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Percentage of Participants With No Cysts at Specified Timepoints
timeFrame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Percentage of Participants With No Pigment Epithelial Detachment at Specified Timepoints
timeFrame: Baseline, Day 7, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Mean Baseline Value and Mean Change From Baseline of Total Area of Choroidal Neovascularization (CNV) at Week 40 and Week 52
timeFrame: Baseline, Week 40, Week 52
measure: Mean Baseline Value and Mean Change From Baseline of Total Area of CNV Component at Week 40 and Week 52
timeFrame: Baseline, Week 40, Week 52
measure: Mean Baseline Value and Mean Change From Baseline of Total Area of Leakage at Week 40 and Week 52
timeFrame: Baseline, Week 40, Week 52
measure: Change From Baseline in the Number of Participants With Anti-Drug Antibodies (ADA) to Faricimab at Anytime Post-Baseline
timeFrame: Predose at Baseline (Day 1), Weeks 16, 24, 28, 44, and 52
measure: Safety Summary: Number and Percentage of Participants With at Least One Adverse Event
timeFrame: From Baseline until 28 days after the last dose of study drug (up to 52 weeks)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Retinal Consultants of Arizona
state: Arizona
city: Tucson
country: United States
facility: Retina Associates Southwest PC
state: Arizona
city: Bakersfield
country: United States
facility: California Retina Consultants
state: California
city: Campbell
country: United States
facility: Retinal Diagnostic Center
state: California
city: Colorado Springs
country: United States
facility: Retina Consultants of Southern Colorado PC; Clinical Research Department
state: Colorado
city: Deerfield Beach
country: United States
facility: Rand Eye
state: Florida
city: Melbourne
country: United States
facility: Florida Eye Associates
state: Florida
city: Saint Petersburg
country: United States
facility: Retina Vitreous Assoc of FL
state: Florida
city: Tallahassee
country: United States
facility: Southern Vitreoretinal Assoc
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Indianapolis
country: United States
facility: Midwest Eye Institute
state: Indiana
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Baltimore
country: United States
facility: The Retina Care Center
state: Maryland
city: Minneapolis
country: United States
facility: Vitreo Retinal Surgery
state: Minnesota
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Albuquerque
country: United States
facility: Eye Associates of New Mexico
state: New Mexico
city: Great Neck
country: United States
facility: Vitreoretinal Consultants
state: New York
city: Eugene
country: United States
facility: Oregon Retina, LLP
state: Oregon
city: Portland
country: United States
facility: Retina Northwest
state: Oregon
city: Germantown
country: United States
facility: Charles Retina Institute
state: Tennessee
city: Abilene
country: United States
facility: Retina Res Institute of Texas
state: Texas
city: Arlington
country: United States
facility: Texas Retina Associates
state: Texas
city: Austin
country: United States
facility: Retina Research Center
state: Texas
city: Willow Park
country: United States
facility: Strategic Clinical Research Group, LLC
state: Texas
city: Salt Lake City
country: United States
facility: Retina Associates of Utah
state: Utah
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
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.