Study to Evaluate Faricimab (RO6867461; RG7716) for Extended Durability in the Treatment of Neovascular Age Related Macular Degeneration (STAIRWAY)

Roche

Status and phase: Completed; Phase 2

Conditions: Macular Degeneration, Age-Related; Neovascularization, Choroidal

Treatments: Drug: Faricimab; Drug: Sham Procedure; Drug: Ranibizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03038880

CR39521

Details and patient eligibility

About

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.

Enrollment: 76 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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76 participants in 3 patient groups

6 mg Faricimab Q12W

Experimental group

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).

Treatment:

Drug: Sham Procedure

Drug: Faricimab

6 mg Faricimab Q16W

Experimental group

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.

Treatment:

Drug: Sham Procedure

Drug: Faricimab

0.5 mg Ranibizumab Q4W

Active Comparator group

Description:

0.5 mg of ranibizumab was administered by IVT injection once every 4 weeks (Q4W) for 48 weeks (13 injections).

Treatment:

Drug: Ranibizumab