Suprachoroidal Injection of CLS-TA Alone or With Aflibercept in Subjects With Diabetic Macular Edema

Study Overview
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Brief Summary
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This study is designed to demonstrate the safety and tolerability of suprachoroidal CLS-TA alone or in combination with intravitreal aflibercept in subjects with diabetic macular edema associated with diabetes mellitus.

Detailed Description
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This is a Phase 1/2, multicenter, open-label study in subject with DME associated with diabetes mellitus. Subjects will be screened and if eligible, will be assigned to study arm at the Baseline Visit (Visit 1, Day 0). Following the Baseline Visit, subjects will participate in six monthly follow-up visits (Visit 2-7; Weeks 4-24) for safety and efficacy assessments and to determine whether additional therapy is needed based upon pre-defined criteria.

Official Title
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Open-Label Study of the Safety and Efficacy of Suprachoroidal CLS-TA Alone or in Combination With Intravitreal Aflibercept for the Treatment of Diabetic Macular Edema

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Drug: IVT Aflibercept
* Drug: SC CLS-TA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women ≥ 18 years of age with type 1 or type 2 diabetes mellitus DME with central involvement (>320 microns in the central subfield on SD-OCT) in the study eye ETDRS BCVA letter score of 83 to 14, inclusive (Snellen equivalent of 20/25 to 20/500) in the study eye Exclusion Criteria: Evidence of DME due to any other cause other than diabetes mellitus in the study eye PRP or focal laser photocoagulation in the study eye within 90 days of screening Intraocular pressure ≥ 22 mmHg or uncontrolled glaucoma (open angle or angle closure) in the study eye History of any previous ophthalmic surgeries in the study eye within 90 days of screening High risk PDR in the study eye, for whom enrollment into the study, in the principal investigator's opinion would put the eye at undue risk for vision loss Any previous treatment in the study eye with ILUVIEN implant Previous treatment for DME in the study eye (TX naive arm only); treatment in the study eye for DME greater than 1 year prior to screening can be considered as treatment naive, at the investigator's discretion Subjects previously treated for DME cannot have been treated in the study eye with an intravitreal injection of anti-VEGF or periocular corticosteroids within 90 days prior to screening (Previous TX arm only) Subjects previously treated for DME cannot have been treated in the study eye with intraocular corticosteroids within 6 months prior to screening (Previous TX arm only)

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TX Naïve Arm<br>Treatment in the TX Naive arm will consist of one unilateral injection of IVT aflibercept in combination with one unilateral injection of SC CLS-TA in the same eye. | Drug: IVT Aflibercept<br>* IVT aflibercept [2 mg (50 µL)]<br>* Other names: Aflibercept;Drug: SC CLS-TA<br>* [4 mg (100 µL)]<br>* Other names: Triamcinolone Acetonide;|
| Experimental: Previous TX Arm<br>Treatment in the Previous TX arm of the study will consist of one unilateral injection of SC CLS-TA. | Drug: SC CLS-TA<br>* [4 mg (100 µL)]<br>* Other names: Triamcinolone Acetonide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Number of participants with treatment emergent adverse events and serious adverse events reported over 6 months of follow-up | Over 6 months of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Intraocular Pressure | Baseline and change from baseline at 6 months in intraocular pressure as measured by applanation tonometry | Baseline and 6 months | 
| Mean Change From Baseline in Central Subfield Thickness | Baseline and change from baseline at 6 months in central subfield thickness. Central subfield thickness (CST) is a diagnostic measurement used in identifying the presence of edema in the circular area 1 mm in diameter centered around the fovea. CST was measured using spectral domain optical coherence tomography (SD-OCT). A masked reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema. | Baseline and 6 months | 
| Best Corrected Visual Acuity | Baseline and Change from baseline at 6 months in best corrected visual acuity before and after treatment Best corrected visual acuity (BCVA) refers to the measurement of the best possible vision that can be achieved following refraction or correction. BCVA was assessed following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol and was measured as the number of letters read correctly on an ETDRS eye chart. A positive change from baseline value represents an improvement in vision. | Baseline and 6 months | 
| CLS-TA Injections | After the initial treatment with CLS-TA, with or without intravitreal aflibercept, at Baseline, retreatment with CLS-TA was allowed in either treatment group from Month 2 through Month 6 if pre-defined retreatment criteria were met. Number of patients receiving 0, 1, 2, 3, 4 or 5 retreatments with CLS-TA. | 2 to 6 months following initial treatment with study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes mellitus, Diabetic retinopathy, Microneedle, Microinjection, Triamcinolone, Choroid, Choroid Injection, Aflibercept, Suprachoroidal, Triamcinolone acetonide