A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Macular Edema Secondary to Central Retinal or Hemiretinal Vein Occlusion

Study Overview
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Brief Summary
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This is a Phase III, multicenter, randomized, double-masked, active comparator-controlled, parallel-group study evaluating the efficacy, safety, and pharmacokinetics of faricimab administered by intravitreal (IVT) injection at 4-week intervals until Week 24, followed by a double-masked period of study without active control to evaluate faricimab administered according to a personalized treatment interval (PTI) dosing regimen in patients with macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO).

Official Title
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A Phase III, Multicenter, Randomized, Double-Masked, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of Faricimab in Patients With Macular Edema Secondary to Central Retinal or Hemiretinal Vein Occlusion

Conditions
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Macular Edema, Central Retinal Vein Occlusion, Hemiretinal Vein Occlusion

Intervention / Treatment
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* Drug: Faricimab
* Drug: Aflibercept
* Procedure: Sham Procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Foveal center-involved macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO), diagnosed no longer than 4 months prior to the screening visit Best-corrected visual acuity (BCVA) of 73 to 19 letters, inclusive (20/40 to 20/400 approximate Snellen equivalent) Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition of good quality retinal images to confirm diagnosis For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs during the treatment period and for 3 months after the final dose of study treatment Exclusion Criteria: Any major illness or major surgical procedure within 1 month before screening Uncontrolled blood pressure Stroke (cerebral vascular accident) or myocardial infarction within 6 months prior to Day 1 Pregnant or breastfeeding, or intending to become pregnant during the study Ocular Exclusion Criteria for Study Eye: History of previous episodes of macular edema due to RVO or persistent macular edema due to RVO diagnosed more than 4 months before screening Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than macular edema due to RVO in the study eye (e.g., ischemic maculopathy, Irvine-Gass syndrome, foveal atrophy, foveal fibrosis, pigment abnormalities, dense subfoveal hard exudates, or other non-retinal conditions) Macular laser (focal/grid) in the study eye at any time prior to Day 1 Panretinal photocoagulation in the study eye within 3 months prior to Day 1 or anticipated within 3 months of study start on Day 1 Any prior or current treatment for macular edema; macular neovascularization, including diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD); and vitreomacular-interface abnormalities, including, but not restricted to, IVT treatment with anti-VEGF, steroids, tissue plasminogen activator, ocriplasmin, C3F8, air or periocular injection Any prior intervention with verteporfin photodynamic therapy, diode laser, transpupillary thermotherapy, or vitreo-retinal surgery including sheathotomy Any prior steroid implant use including dexamethasone intravitreal implant (Ozurdex) and fluocinolone acetonide intravitreal implant (Iluvien) Ocular Exclusion Criteria for Both Eyes: Prior IVT administration of faricimab in either eye History of idiopathic or autoimmune-associated uveitis in either eye Active periocular, ocular or intraocular inflammation or infection (including suspected) in either eye on Day 1

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)<br>In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm A will receive faricimab 6 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants will receive faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure will be administered during study visits at which no faricimab treatment is administered (according to the PTI dosing regimen). | Drug: Faricimab<br>* Faricimab will be administered by intravitreal (IVT) injection as specified in each treatment arm.<br>* Other names: RO6867461;Procedure: Sham Procedure<br>* The sham is a procedure that mimics an IVT injection, but involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.<br>|
| Active Comparator: Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)<br>In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm B will receive aflibercept 2 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants will receive faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure will be administered during study visits at which no faricimab treatment is administered (according to the PTI dosing regimen). | Drug: Faricimab<br>* Faricimab will be administered by intravitreal (IVT) injection as specified in each treatment arm.<br>* Other names: RO6867461;Drug: Aflibercept<br>* Aflibercept 2 mg will be administered by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections).<br>* Other names: Eylea;Procedure: Sham Procedure<br>* The sham is a procedure that mimics an IVT injection, but involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Change from Baseline in Best-Corrected Visual Acuity (BCVA) at Week 24 |  | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Change from Baseline in BCVA at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline at Week 24 |  | Baseline and Week 24 | 
| Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Percentage of Participants Gaining ≥10 Letters in BCVA from Baseline at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Percentage of Participants Gaining ≥5 Letters in BCVA from Baseline at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Percentage of Participants Gaining >0 Letters in BCVA from Baseline at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA from Baseline at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA from Baseline at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA from Baseline at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Percentage of Participants Achieving ≥84 Letters (20/20 Snellen Equivalent) in BCVA at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Percentage of Participants Achieving ≥69 Letters (20/40 or Better Snellen Equivalent) in BCVA at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Percentage of Participants with ≤38 Letters (20/200 or Worse Snellen Equivalent) in BCVA at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Change from Baseline in Central Subfield Thickness at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Percentage of Participants with Absence of Macular Edema at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Percentage of Participants with Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Percentage of Participants with Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Percentage of Participants with Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24 |  | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| Part 1: Change from Baseline in National Eye Institute 25-Item Visual Functioning Questionnaire (NEI VFQ-25) Composite Score at Week 24 |  | Baseline and Week 24 | 
| Parts 1 and 2: Change from Baseline in BCVA at Specified Timepoints Through Week 72 |  | Baseline and every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline at Specified Timepoints Through Week 72 |  | Baseline and every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Percentage of Participants Gaining ≥10 Letters in BCVA from Baseline at Specified Timepoints Through Week 72 |  | Baseline and every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Percentage of Participants Gaining ≥5 Letters in BCVA from Baseline at Specified Timepoints Through Week 72 |  | Baseline and every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Percentage of Participants Gaining >0 Letters in BCVA from Baseline at Specified Timepoints Through Week 72 |  | Baseline and every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA from Baseline at Specified Timepoints Through Week 72 |  | Baseline and every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA from Baseline at Specified Timepoints Through Week 72 |  | Baseline and every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA from Baseline at Specified Timepoints Through Week 72 |  | Baseline and every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Percentage of Participants Achieving ≥84 Letters (20/20 Snellen Equivalent) in BCVA at Specified Timepoints Through Week 72 |  | Every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Percentage of Participants Achieving ≥69 Letters (20/40 or Better Snellen Equivalent) in BCVA at Specified Timepoints Through Week 72 |  | Every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Percentage of Participants with ≤38 Letters (20/200 or Worse Snellen Equivalent) in BCVA at Specified Timepoints Through Week 72 |  | Every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Change from Baseline in NEI VFQ-25 Questionnaire Composite Score at Specified Timepoints Through Week 72 |  | Baseline, Weeks 24, 48, and 72 | 
| Parts 1 and 2: Change from Baseline in Central Subfield Thickness at Specified Timepoints Through Week 72 |  | Baseline and every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Percentage of Participants with Absence of Macular Edema at Specified Timepoints Through Week 72 |  | Baseline and every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Percentage of Participants with Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 72 |  | Baseline and every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Percentage of Participants with Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 72 |  | Baseline and every 4 weeks from Week 4 to Week 72 | 
| Parts 1 and 2: Percentage of Participants with Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 72 |  | Baseline and every 4 weeks from Week 4 to Week 72 | 
| Part 2: Change from Week 24 in BCVA at Specified Timepoints Through Week 72 |  | Every 4 weeks from Week 24 to Week 72 | 
| Part 2: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA from Week 24 at Specified Timepoints Through Week 72 |  | Every 4 weeks from Week 24 to Week 72 | 
| Part 2: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA from Week 24 at Specified Timepoints Through Week 72 |  | Every 4 weeks from Week 24 to Week 72 | 
| Part 2: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA from Week 24 at Specified Timepoints Through Week 72 |  | Every 4 weeks from Week 24 to Week 72 | 
| Part 2: Percentage of Participants Avoiding a Loss of >0 Letters in BCVA from Week 24 at Specified Timepoints Through Week 72 |  | Every 4 weeks from Week 24 to Week 72 | 
| Part 2: Percentage of Participants on Different Treatment Intervals at Week 68 |  | Week 68 | 
| Part 2: Number of Study Drug Injections Received from Week 24 Through Week 72 |  | From Week 24 to Week 72 | 
| Incidence and Severity of Ocular Adverse Events, with Severity Determined According to Adverse Event Severity Grading Scale |  | From Baseline until end of study (up to 72 weeks) | 
| Incidence and Severity of Non-Ocular Adverse Events, with Severity Determined According to Adverse Event Severity Grading Scale |  | From Baseline until end of study (up to 72 weeks) | 
| Plasma Concentration of Faricimab Over Time |  | Predose at Day 1, Weeks 4, 24, 28, 52, and 72 | 
| Number of Participants with Anti-Drug Antibodies (ADAs) to Faricimab at Baseline and During the Study |  | Predose at Day 1 (Baseline), Weeks 4, 24, 28, 52, and 72 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRVO, HRVO