A Study to Evaluate the Efficacy and Safety of Faricimab in Patients With Choroidal Neovascularization Secondary to Pathologic Myopia

Study Overview
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Brief Summary
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This is a Phase III, multicenter, randomized, double-masked, active comparator-controlled study evaluating the efficacy and safety of faricimab in patients with myopic choroidal neovascularization (CNV). This non-inferiority study will compare 6.0 mg faricimab versus 0.5 mg ranibizumab administered at a pro-re-nata (PRN) dosing regimen after an initial active IVT treatment administration at randomization (Day 1).

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 Choroidal Neovascularization Secondary to Pathologic Myopia

Conditions
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Choroidal Neovascularization Secondary to Pathologic Myopia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment-naïve choroidal neovascularization (CNV) secondary to myopia Diagnosis of active myopic CNV in the study eye: Presence of high myopia, worse than -6 diopters of spherical equivalence Antero-posterior elongation measurement greater than or equal to 26.0 mm Presence of posterior changes compatible with pathologic myopia (e.g., tessellated fundus, lacquer cracks, etc.) Presence of active leakage from CNV on FFA (determined by Central Reading Centre [CRC]) Presence of intraretinal or subretinal fluid or increase of CST on OCT (determined by CRC) BCVA of 78 to 24 letters, inclusive (20/32 to 20/320 approximate Snellen equivalent), using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol on Day 1 Overtly healthy as determined by medical evaluation that includes medical history, physical examination, and laboratory tests Ability to comply with the study protocol, in the Investigator's judgment Other protocol-defined inclusion criteria apply Exclusion Criteria: Any major illness or major surgical procedure within 1 month before screening Pregnancy or breastfeeding, or intention to become pregnant during the study or within 3 months after the final study treatment administration Uncontrolled blood pressure (systolic >180 millimetres of mercury [mmHg], diastolic >100 mmHg) Stroke (cerebral vascular accident) or myocardial infarction within 6 months prior to Day 1 History of systemic or ocular disease that would contraindicate treatment with the investigational drug or comparator Uncontrolled glaucoma in study eye Any prior or concomitant treatment for CNV or vitreomacular-interface abnormalities, including, but not restricted to, intravitreal, periocular or laser interventions in study eye Prior or concomitant periocular or intravitreal pharmacological treatment, including anti-VEGF medication, for other retinal diseases (e.g. geography atrophy, nAMD, DME etc.) in study eye Other protocol-defined exclusion criteria apply

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<br>All participants randomly assigned to Arm A will receive faricimab 6 mg at Day 1. Once every 4 weeks (Q4W) after Day 1, participants will receive treatment with faricimab on a pro re nata (PRN) basis dependent on prespecified retreatment criteria. | Drug: Faricimab<br>* Faricimab 6 mg intravitreal (IVT) injection on Day 1 with Q4W PRN treatment thereafter to Week 44. At Week 48, participants will attend a follow-up visit.<br>* Other names: RG7716;Procedure: Sham Procedure<br>* The sham is a procedure that mimics an intravitreal (IVT) injection, but involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. Participants will undergo the sham procedure at study visits where no study drug is to be administered, in order to maintain masking.<br>|
| Active Comparator: Arm B: Ranibizumab<br>All participants randomly assigned to Arm B will receive ranibizumab 0.5 mg at Day 1. Once every 4 weeks (Q4W) after Day 1, participants will receive treatment with ranibizumab on a pro re nata (PRN) basis dependent on prespecified retreatment criteria. | Drug: Ranibizumab<br>* Ranibizumab 0.5 mg intravitreal (IVT) injection on Day 1 with Q4W PRN treatment thereafter to Week 44. At Week 48, participants will attend a follow-up visit.<br>* Other names: Lucentis;Procedure: Sham Procedure<br>* The sham is a procedure that mimics an intravitreal (IVT) injection, but involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. Participants will undergo the sham procedure at study visits where no study drug is to be administered, in order to maintain masking.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Best-Corrected Visual Acuity (BCVA) Averaged Over Weeks 4, 8, and 12 |  | Baseline and Average of Weeks 4, 8, and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in BCVA Over Time |  | From Baseline through Week 48 | 
| Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline Averaged Over Weeks 4, 8, and 12 |  | Baseline and Average of Weeks 4, 8, and 12 | 
| Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline Over Time |  | From Baseline through Week 48 | 
| Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA from Baseline Over Time |  | From Baseline through Week 48 | 
| Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline or Achieving a BCVA of ≥84 Letters Over Time |  | From Baseline through Week 48 | 
| Percentage of Participants with BCVA Snellen Equivalent of 20/40 or Better Over Time |  | From Baseline through Week 48 | 
| Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse Over Time |  | From Baseline through Week 48 | 
| Percentage of Participants Only Receiving One Injection From Baseline to Weeks 12, 24, and 48 |  | From Baseline to Weeks 12, 24, and 48 | 
| Number of Intravitreal Injections Received From Baseline to Weeks 12, 24, and 48 |  | From Baseline to Weeks 12, 24, and 48 | 
| Change from Baseline in Central Subfield Thickness (CST) of the Study Eye Averaged Over Weeks 4, 8, and 12 |  | Baseline and Average of Weeks 4, 8, and 12 | 
| Change from Baseline in CST of the Study Eye Over Time |  | From Baseline through Week 48 | 
| Change from Baseline in Total Area of the Choroidal Neovascularization Lesion at Weeks 12 and 48 |  | Baseline, Weeks 12 and 48 | 
| Change from Baseline in Total Area of the Choroidal Neovascularization Leakage at Weeks 12 and 48 |  | Baseline, Weeks 12 and 48 | 
| Percentage of Participants with Absence of Macular Leakage at Weeks 12 and 48 |  | Weeks 12 and 48 | 
| Incidence and Severity of Ocular Adverse Events |  | From first dose until 35 days after the last dose of study treatment (up to 48 weeks) | 
| Incidence and Severity of Non-Ocular Adverse Events |  | From first dose until 35 days after the last dose of study treatment (up to 48 weeks) | 
| Prevalence of Anti-Drug Antibodies (ADAs) at Baseline and Incidence of ADAs During the Study |  | At Baseline and from first dose until end of study (up to 48 weeks) |