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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
A Multicenter, Open-Label Extension Study to Evaluate the Long-Term Safety and Tolerability of Faricimab in Patients With Neovascular Age-Related Macular Degeneration (AVONELLE-X)

Conditions
-----------------
Neovascular Age-related Macular Degeneration

Intervention / Treatment
-----------------
* Drug: Faricimab
* Other: Sham Procedure


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Main Study: Faricimab PTI<br> | Drug: Faricimab<br>* Faricimab 6 mg will be administered by intravitreal (IVT) injection into the study eye according to the personalized treatment interval (PTI) dosing regimen for the duration of the study.<br>* Other names: RG7716;Other: Sham Procedure<br>* 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.<br>|
| Experimental: Substudy: Faricimab PTI<br> | Drug: Faricimab<br>* Faricimab 6 mg will be administered by intravitreal (IVT) injection into the study eye according to the personalized treatment interval (PTI) dosing regimen for the duration of the study.<br>* Other names: RG7716;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Main Study: Incidence and Severity of Ocular Adverse Events |  | Up to 2 years | 
| Main Study: Incidence and Severity of Systemic (Non-Ocular) Adverse Events |  | Up to 2 years | 
| Main Study: Number of Participants with Presence of Anti-Drug Antibodies (ADAs) at Baseline and Incidence of ADAs During the Study |  | From Baseline 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 | 1 Year is defined as the earliest substudy visit closest to Week 52 occurring between Week 48 and Week 64. | Baseline and 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Substudy: Percent Change in Corneal Endothelial Cell Density From Baseline at Week 24 in the Study Eye as Compared With the Fellow Eye | Week 24 is defined as the earliest substudy visit closest to Week 24 occurring between Week 20 and Week 28. | Baseline and Week 24 |