A Study to Evaluate ASP8232 in Reducing Central Retinal Thickness in Subjects With Diabetic Macular Edema (DME)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate efficacy and safety of ASP8232 in subjects with diabetic macular edema (DME). This study will evaluate the percent change from baseline in excess central subfield thickness (CST) in the study eye as assessed by spectral domain-optical coherence Tomography (SD-OCT) for ASP8232 monotherapy at Month 3.

Official Title
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A Phase 2, Double-Masked, Randomized, Active Controlled Study to Evaluate the Efficacy and Safety of ASP8232 in Reducing Central Retinal Thickness in Subjects With Diabetic Macular Edema

Conditions
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Diabetes Mellitus, Diabetic Macular Edema

Intervention / Treatment
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* Drug: ASP8232
* Drug: ranibizumab
* Drug: Placebo
* Other: Sham intravitreal (IVT) injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must have a documented diagnosis of type 1 or type 2 diabetes mellitus and a glycosylated hemoglobin A1c (HbA1c) of ≤ 12.0% at Screening Subject has definite retinal thickening due to diffuse diabetic macular edema (DME) involving the central macula based on evaluating investigator's clinical evaluation and demonstrated by spectral domain-optical coherence tomography (SD-OCT) Subject has central subfield thickness (CST) of at least 375 μm by SD-OCT with presence of intraretinal and/or subretinal fluid at screening visit and at the randomization visit Subject has early treatment diabetic retinopathy study (ETDRS) best corrected visual acuity (BCVA) letter score ≤ 73 (Snellen 20/40) and ≥ 24 (Snellen 20/320) at screening visit Exclusion Criteria: Subject's study eye has macular edema considered to be due to a cause other than DME Subject's study eye has a decrease in BCVA due to causes other than DME that is likely to be decreasing BCVA by 3 lines or more Subject's study eye has significant macular ischemia as shown on angiography Subject's study eye has any other ocular disease that may cause substantial reduction in BCVA Subject has active peri-ocular or ocular infection Subject's study eye has a history of non-infectious uveitis Subject's study eye has high myopia (-8 diopter or more correction) Subject's study eye has a history of prior pars plana vitrectomy Subject's study eye has a history of any ocular surgery within 3 months prior to Day 1 Subject's study eye has a history of YAG capsulotomy within 3 months prior to Day 1 Subject's study eye has a history of panretinal scatter photocoagulation (PRP) or focal laser within 3 months prior to Day 1 or anticipated need for PRP during the course of the study through the Week 12 visit Subject's study eye has a history of prior IVT, subtenon, or periocular, non-sustained release, steroid therapy within 3 months prior to Day 1 Subject's study eye has a history of intravitreal sustained release dexamethasone therapy within 6 months prior to Day 1. Subject's study eye has a history of intravitreal sustained release fluocinolone within 3 years prior to Day 1. Subject's study eye has a history of prior treatment for DME with IVT anti-vascular endothelial growth factor (VEGF) treatment within 8 weeks prior to Day 1 Subject has a history of prior treatment with any other (than previously listed) approved treatment which is not labeled for DME within 1 year prior to Day 1 Subject's study eye has high-risk proliferative diabetic retinopathy (PDR) Subject has uncontrolled glaucoma Subject has media clarity, papillary constriction (i.e., senile miosis), or subject lacks cooperation that would interfere with any study procedures, evaluations or interpretation of data

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: ASP8232 + sham intravitreal (IVT) injections<br>ASP8232 will be given orally once daily and sham injections 3 times with 1 month intervals | Drug: ASP8232<br>* oral capsule<br>Other: Sham intravitreal (IVT) injection<br>* intravitreal (IVT) injection<br>|
| Experimental: ASP8232 + ranibizumab intravitreal (IVT) injections<br>ASP8232 will be given orally once daily and ranibizumab injections 3 times with 1 month intervals | Drug: ASP8232<br>* oral capsule<br>Drug: ranibizumab<br>* intravitreal (IVT) injection<br>* Other names: Lucentis;|
| Active Comparator: Placebo + ranibizumab intravitreal (IVT) injections<br>Placebo will be given orally once daily and ranibizumab injections 3 times with 1 month intervals | Drug: ranibizumab<br>* intravitreal (IVT) injection<br>* Other names: Lucentis;Drug: Placebo<br>* oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in excess central subfield thickness (CST) in the study eye as assessed by spectral domain-optical coherence tomography (SD-OCT) at Month 3 |  | Baseline and Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change from baseline in CST in the study eye as assessed by SD-OCT at Month 3 |  | Baseline and Month 3 | 
| Change from baseline in early treatment diabetic retinopathy study (ETDRS) best corrected visual acuity (BCVA) score in the study eye at Month 3 |  | Baseline and Month 3 | 
| Absolute and percent change from baseline in excess CST in the study eye as assessed by SD-OCT at Months 1 and 2 |  | Baseline and Months 1, 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASP8232, Diabetes Mellitus, ranibizumab, Diabetic Macular Edema