Treat & Extend Versus Fixed Dosing With Faricimab for Management of Diabetic Macular Edema: A Pragmatic, Multi-center, Open-label, Randomized, Controlled Trial

Study Overview
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Brief Summary
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This study will assess a pragmatic, treat and extend regimen of faricimab against the standard of a fixed dosing regimen.

Official Title
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Treat & Extend Versus Fixed Dosing With Faricimab for Management of Diabetic Macular Edema: A Pragmatic, Multi-center, Open-label, Randomized, Controlled Trial

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Drug: Faricimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Diagnosis of diabetes mellitus (type 1 or type 2). Macular thickening secondary to DME (CI-DME) involving the center of the fovea on Optical Coherence Tomography - Central subfield thickness (CST) ≥ 325 μm on Spectralis at screening.*** Visual impairment due to DME, with best corrected visual acuity of 80 to 20 letters (Snellen VA 20/25 - 20/400). Media clarity, pupillary dilation, and individual cooperation sufficient for adequate OCT and fundus photographs. Hemoglobin A1c must be <10% within 2 months prior to 1st study treatment. Provide signed informed consent. Exclusion Criteria: Active or history of ocular inflammation or suspected/active ocular infection in either eye. High-risk proliferative diabetic retinopathy in the study eye.** Tractional retinal detachment, preretinal fibrosis or visually significant epiretinal membrane involving the macula. Uncontrolled glaucoma (intraocular pressure >30 with or without medications). Any intravitreal, periocular or implant corticosteroids within 26 weeks (6 months) before day 1 or any use of Iluvien implants. Treatment with Panretinal photocoagulation (PRP) within 12 weeks before day 1. Treatment with macular laser. Any cataract surgery or any other intraocular surgery within 12 weeks before day 1. Macular edema in study eye due to a cause other than DME. If clinical exam and/or OCT and/or wide-field fluorescein angiography (WF-FA) suggest that (a) macular edema is considered to be related to ocular surgery such as cataract extraction or (b) if primary cause for macular edema is vitreoretinal interface abnormalities (e.g. a taut posterior hyaloid or epiretinal membrane). Any ocular condition is present such that visual acuity loss would not improve from resolution of macular edema in opinion of the investigator (e.g. foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition) Any history of ocular conditions that might affect macular edema (e.g. vein occlusion, idiopathic or infectious or non-infectious uveitis, ocular inflammatory disease, neovascular glaucoma etc.) Women of child-bearing potential who are lactating, pregnant, or intending to become pregnant within the next 100 weeks. Current or anticipated incarceration. Terminal illness with expected survival less than 100 weeks. Known hypersensitivity to faricimab or any of the excipients in the faricimab injection. Currently enrolled in a study that does not permit co-enrollment. Unable to obtain informed consent due to language or other operational barriers. Anticipated problems, in the judgment of the site investigator, maintaining compliance with the protocol, including attending study visits, completing assessments or procedures. Prior enrollment in this trial. Other reason to exclude the patient, as approved by the sponsor and site investigator. Previous treatment with anti-VEGF and: <12 weeks prior to day 1 (washout period).*or, Diagnosis of DME is > 2 years of enrollment or, Do not have a demonstrated response to anti-VEGF treatment based on clinical discretion.

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
Interventional Model Description: Two-armed, parallel, non-inferiority randomized controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treat and Extend<br>Participants randomized to the T&E Arm will initially receive 6 milligrams (mg) faricimab intravitreal (IVT) injections monthly (28d +/-7 days), with treatment intervals increased/extended, reduced, or maintained based on CST assessments, until week 100. | Drug: Faricimab<br>* Faricimab will be administered via intravitreal injection.<br>|
| Other: Control/Usual Care Arm<br>Participants in the control arm will receive 6 milligrams (mg) faricimab intravitreal (IVT) injections monthly (28d +/-7 days), for 6 treatments. Afterwards, participants will continue to receive 6mg faricimab IVT every 8 weeks until week 100. | Drug: Faricimab<br>* Faricimab will be administered via intravitreal injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Best Corrected Visual Acuity | Change in best corrected visual acuity (3.9 letter non-inferiority margin) | Baseline to Week 100 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in Diabetic Retinopathy Severity Score | A 2-step improvement in diabetic retinopathy severity score | Baseline to Week 100 | 
| Decrease in Diabetic Retinopathy Severity Score | A 3-step improvement in diabetic retinopathy severity score | Baseline to Week 100 | 
| Change in Central Subfield Thickness | Change in central subfield thickness on OCT | Baseline to Week 100 | 
| Change in Vision Related Quality of Life | Change in vision-related quality of life (VFQ-25) | Baseline to Week 100 | 
| Change in Letters of Vision | Gaining or losing ≥5, ≥10, or ≥15 letters of vision | Baseline to Week 100 | 
| Absence of Diabetic Macular Edema | Absence of diabetic macular edema in the study eye | Week 100 | 
| Absence of Intraretinal Fluid (IRF) | Absence of intraretinal fluid (IRF) in the study eye | Week 100 | 
| Dosing Interval | Dosing interval at week 100 | Week 100 | 
| Presence of Safety Outcomes | Safety outcomes (ocular and systemic AEs and SAEs) | Baseline to Week 100 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treat and Extend, Faricimab, Anti-VEGF