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

• ASP8232 (Drug): oral capsule
• ranibizumab (Drug), also known as Lucentis: intravitreal (IVT) injection
• Placebo (Drug): oral capsule
• Sham intravitreal (IVT) injection (Other): intravitreal (IVT) injection

Primary outcomes

• 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 outcomes

• 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]

Sex: All, ages: 18 Years to 85 Years

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

• Results publication: Nguyen QD, Sepah YJ, Berger B, Brown D, Do DV, Garcia-Hernandez A, Patel S, Rahhal FM, Shildkrot Y, Renfurm RW; VIDI Research Group. Primary outcomes of the VIDI study: phase 2, double-masked, randomized, active-controlled study of ASP8232 for diabetic macular edema. Int J Retina Vitreous. 2019 Aug 1;5:28. doi: 10.1186/s40942-019-0178-7. eCollection 2019. PMID 31388454

• Global Medical Lead, Study director, Astellas Pharma Europe B.V.