A Study of Intravitreal ILUVIEN® Implant as Baseline Therapy in Patients With Early Diabetic Macular Edema (DME)

Study Overview
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Brief Summary
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This is a randomized, masked, active-controlled, parallel-group, multi-center study that will assess the efficacy of ILUVIEN as a baseline therapy in the treatment of Center Involving DME (CI-DME). The study will enroll patients who are either treatment naïve or have not received any DME treatments for the preceding 12 months as documented in medical records. Patients who received DME treatment >12 months before screening, must not have received >4 intravitreal injections. The study will compare 2 treatment regimens: ILUVIEN intravitreal implant (0.19 mg) followed by supplemental aflibercept as needed per protocol criteria (2 mg/0.05 mL), compared to intravitreal aflibercept loading dose (2 mg administered by intravitreal injection every 4 weeks for 5 consecutive doses) followed by supplemental aflibercept as needed per protocol criteria (2 mg/0.05 mL).

Official Title
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A Randomized, Masked, Controlled Study of Intravitreal ILUVIEN® Implant as Baseline Therapy in Patients With Early Diabetic Macular Edema (DME)

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Drug: Iluvien 0.19 MG Drug Implant
* Drug: Aflibercept


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Male or female subjects ≥18 years of age at the time of consent. Must have CI-DME confirmed by Spectral Domain Ocular Coherence Tomography (SD-OCT) and Center Subfield Thickness (CST) of: ≥350 µm in the study eye. Best Corrected Visual Acuity (BCVA) of ≤80 ETDRS Letters and ≥35 ETDRS letters in the study eye at Screening Visit. Major Exclusion Criteria: Patients with Proliferative Diabetic Retinopathy (PDR); high risk proliferative diabetic retinopathy in the study eye and related complications. History or current diagnosis of glaucoma or ocular hypertension (OHT) or a cup to disc ratio >0.8; History of uncontrolled intraocular pressure (defined as IOP ≥25 mmHg with maximum topical and systemic medical hypotensive treatment) or previous filtration surgery in the study eye at Screening Visit. Other conditions that can cause macular edema. Patients who received prior LASER photocoagulation therapy including macular grid or pan retina photocoagulation (PRP) at any time in the study eye. Prior focal LASER photocoagulation therapy outside the macula is allowed. Patients who received the following therapies in the study eye: Intravitreal or periocular steroids; Intravitreal injection of aflibercept, brolucizumab, or conbercept ≤12 months prior to Screening Visit Patients who received >1 intravitreal injection of ranibizumab or bevacizumab in the last 12 months; or have received ranibizumab or bevacizumab ≤6 weeks prior to Screening Visit Patients who have lens opacities due to cataract or other etiologies that would make it difficult to examine the fundus or that affect the patients Activities of Daily Living (ADL). Steroid Challenge Exclusion Criterion- At the Baseline Visit, patients who are determined to have an IOP ≥25 mmHg or an increase ≥8 mmHg from Screening will be excluded from the study.

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: Randomized, masked, active-controlled, multi-center study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ILUVIEN Arm<br>Intravitreal ILUVIEN | Drug: Iluvien 0.19 MG Drug Implant<br>* 0.19 mg Fluocinolone Acetonide Intravitreal Implant<br>* Other names: ILUVIEN;Drug: Aflibercept<br>* 2 mg/0.05 mL Aflibercept Anti-VEGF intravitreal injection<br>* Other names: Eylea;|
| Active Comparator: Aflibercept Arm<br>Intravitreal aflibercept | Drug: Aflibercept<br>* 2 mg/0.05 mL Aflibercept Anti-VEGF intravitreal injection<br>* Other names: Eylea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The mean total number of supplemental aflibercept injections needed during the study | The mean total number of supplemental aflibercept injections needed during | Baseline to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with 15, 10 and 5 letter (ETDRS) gains from baseline | Proportion of subjects with 15, 10 and 5 letter (ETDRS) gains from baseline | At 18 months | 
| Area under the curve (AUC) of Best Corrected Visual Acuity (BCVA) | Area under the curve (AUC) of Best Corrected Visual Acuity (BCVA) | Baseline to 18 months | 
| Mean change from baseline in Center Subfield Thickness (CST) | Mean change from baseline in Center Subfield Thickness (CST) | Baseline to 18 months | 
| Area under the curve (AUC) of Center Subfield Thickness (CST) | Area under the curve (AUC) of Center Subfield Thickness (CST) | Baseline to 18 months | 
| Mean change from baseline in the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) composite score and subscale scores | The NEI VFQ-25 is a questionnaire that allows the individual to report on their level of visual function. Scores range from 0-100, with a score of 0 being the worst outcome and 100 being the best outcome. | At 18 months | 
| Safety Outcome Endpoints: The incidence and severity of treatment-related adverse events | The incidence and severity of treatment-related adverse events | Baseline to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DME, CI-DME, Diabetic Macular Edema, Diabetic Retinopathy