A Study to Evaluate the Long-Term Safety and Tolerability of Faricimab in Participants With Neovascular Age-Related Macular Degeneration

Hoffmann-La Roche1,036 enrolled

Overview

This main long-term extension study is designed to evaluate the long-term safety and tolerability of faricimab 6 milligrams (mg) administered by intravitreal injection at a personalized treatment interval (PTI) to participants with neovascular age-related macular degeneration (nAMD) who enrolled in and completed one of the Phase III studies: GR40306 (NCT03823287) or GR40844 (NCT03823300), also referred to as the parent studies. Eligible patients who consent to participate in this main study will be enrolled upon completion of the end-of-study visit in the parent study. Additionally, there is a substudy that is being conducted. The aim of this substudy is to evaluate the impact of intravitreal faricimab on the health of the corneal endothelial cells in the study eyes of patients with nAMD to fulfill a U.S. Food and Drug Administration (FDA) post-marketing requirement. The fellow eyes of the same enrolled participants in the substudy will serve as the controls.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

1,036

Conditions

Neovascular Age-related Macular Degeneration

Interventions

Sham ProcedureOTHER

The sham is a procedure that mimics an IVT injection and involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. The sham procedure will be administered to participants as appropriate during the first 12 weeks of this study in order to maintain the masking of the initial faricimab PTI.

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria for the Main Study: * Previous enrollment in and completion of Study GR40306 (NCT03823287) or Study GR40844 (NCT03823300), without study or study drug discontinuation * For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs. Women must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 3 months after the final dose of faricimab. Women must refrain from donating eggs during the same period. Inclusion Criteria for the Substudy: * In addition to all inclusion criteria specified in the main Study GR42691, participants in the Substudy must meet the following criteria: * Sign an informed consent form for the Substudy * Must be able to participate for at least 48 weeks in the Substudy and have at least the first visit while enrolled in the main Study GR42691 * A difference of \<10% in corneal endothelial cell density at screening between the two eyes as measured by specular microscopy and determined by the independent reading center Exclusion Criteria for the Main Study: * Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of faricimab * Presence of other ocular diseases that give reasonable suspicion of a disease or condition that contraindicates the use of faricimab, that might affect interpretation of the results of the study or that renders the patient at high risk for treatment complications * Presence of other diseases, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of faricimab and that might affect interpretation of the results of the study or that renders the patient at high risk of treatment complications * History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the faricimab injections, study-related procedure preparations, dilating drops, or any of the anesthetic and antimicrobial preparations used by a patient during the study * Requirement for continuous use of any medications or treatments indicated as prohibited therapy Exclusion Criteria for the Substudy: In addition to the exclusion criteria specified in the main Study GR42691, patients will be excluded from this substudy if they meet any of the following exclusion criteria: * Prior and/or current administration of faricimab in the fellow (non-study) eye * Prior administration of brolucizumab in the fellow (non-study) eye Exclusion Criteria in Either Eye for the Substudy: * Corneal endothelial cell density ≤1500 cells/mm2 in either eye at screening as determined by the independent corneal reading center * Fuchs endothelial corneal dystrophy Grade ≥2 * Previous ocular trauma (blunt or penetrating) and/or corneal endothelial cell damage, including from blunt or surgical trauma (including complicated cataract surgery resulting in complicated lens placement such as anterior chamber intraocular lens, sulcus intraocular lens, aphakia, etc.) * Any ocular condition that precludes obtaining an analyzable specular microscopy image * Active or history of corneal edema * Any active or history of corneal dystrophies, excluding Fuchs endothelial corneal dystrophy Grade \<2 * Active or history of iridocorneal endothelial syndrome * Active or history of pseudoexfoliation syndrome * Active or history of herpetic keratitis or kerato-uveitis (including herpes simplex virus and herpes zoster virus) * Intraocular laser therapy including selective laser trabeculoplasty, yttrium-aluminum garnet (YAG), prophylactic peripheral iridotomy within 1 year of screening, or YAG capsulotomy within 3 months of screening * Prior vitrectomy surgery, submacular surgery, or other surgical intervention for AMD * Prior pars plana vitrectomy surgery * Previous intraocular device implantation excluding intraocular lenses * Cataract surgery within 6 months of screening or planned for during the study * History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery. Other types of prior glaucoma surgery are allowed providing that the surgery occur more than 6 months before screening * Administration of topical Rho kinase inhibitors (e.g., Rhopressa eye drops) within 1 month prior to the screening visit * Contact lens wear in either eye within 2 months of screening * History of corneal transplantation, including partial-thickness corneal grafts (e.g., Descemet membrane endothelial keratoplasty, Descemet stripping endothelial keratoplasty) * Active or history of iridocorneal endothelial syndrome * Active or history of pseudoexfoliation syndrome

Locations (251)

Barnet Dulaney Perkins Eye Center

Mesa, Arizona, United States

Arizona Retina and Vitreous Consultants

Phoenix, Arizona, United States

Associated Retina Consultants

Phoenix, Arizona, United States

Retina Associates Southwest PC

Tucson, Arizona, United States

Retinal Diagnostic Center

Campbell, California, United States

Outcomes

Primary Outcomes

Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale

This is an analysis of participants with at least one ocular adverse event (AE) that occurred in the study eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of the seriousness, severity (e.g., mild, moderate, or severe intensity), and causality for each AE. AEs of special interest (AESI) included the following: Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, are associated with severe intraocular inflammation (IOI), or require surgical or medical intervention to prevent permanent loss of sight; suspected transmission of an infectious agent by the study drug; and, cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.

Time frame: From the date of first administration of faricimab through 28 days after the end of study (up to 2 years)

Incidence of Ocular Adverse Events in the Fellow Eye

This is an analysis of participants with at least one ocular adverse event (AE) that occurred in the study eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of the seriousness, severity, and causality for each AE. AEs of special interest (AESI) included the following: Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, are associated with severe intraocular inflammation (IOI), or require surgical or medical intervention to prevent permanent loss of sight; suspected transmission of an infectious agent by the study drug; and, cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.

Time frame: From the date of first administration of faricimab through 28 days after the end of study (up to 2 years)

Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale

This is an analysis of participants with at least one non-ocular (systemic) adverse event (AE). Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of the seriousness, severity (e.g., mild, moderate, or severe intensity), and causality for each AE. AEs of special interest (AESI) included the following: Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, are associated with severe intraocular inflammation (IOI), or require surgical or medical intervention to prevent permanent loss of sight; suspected transmission of an infectious agent by the study drug; and, cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.

Time frame: From the date of first administration of faricimab through 28 days after the end of study (up to 2 years)

Substudy: Percent Change in Corneal Endothelial Cell Density From Baseline at 1 Year in the Study Eye as Compared With the Fellow Eye

Specular microscopy was performed for both eyes prior to application of any topical ophthalmic anesthetic, tonometry, or any other study treatment on the same day for the evaluation of corneal endothelial cell (CEC) density. The 1-year timepoint was defined as the earliest substudy visit closest to Week 52 occurring between Week 48 and Week 64. Data (from both study eye and fellow eye) collected after the fellow eye's use of prohibited therapies-such as faricimab, brolucizumab, bevacizumab, and Port Delivery System implantation-were excluded from the corneal endothelial cell analysis.

Time frame: Baseline and 1 year

Secondary Outcomes

Substudy: Percent Change in Corneal Endothelial Cell Density From Baseline at Week 24 in the Study Eye as Compared With the Fellow Eye

Specular microscopy was performed for both eyes prior to application of any topical ophthalmic anesthetic, tonometry, or any other study treatment on the same day for the evaluation of corneal endothelial cell (CEC) density. The Week 24 timepoint was defined as the earliest substudy visit closest to Week 24 occurring between Week 20 and Week 28. Data (from both study eye and fellow eye) collected after the fellow eye's use of prohibited therapies-such as faricimab, brolucizumab, bevacizumab, and Port Delivery System implantation-were excluded from the corneal endothelial cell analysis.

Time frame: Baseline and Week 24