A Phase 2 Study to Assess the Efficacy and Safety of KHK4951 in Patients With Diabetic Macular Edema

Study Overview
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Brief Summary
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The purpose of this study is to evaluate efficacy and safety of KHK4951 eye drops in patients with DME.

Official Title
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A Phase 2, Multicenter, Randomized, Double-Masked, Parallel-Group Study to Assess the Efficacy and Safety of KHK4951, a Vascular Endothelial Growth Factor Receptor Inhibitor, in Patients With Diabetic Macular Edema

Conditions
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Diabetic Macular Edema (DME)

Intervention / Treatment
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* Drug: KHK4951
* Drug: Aflibercept Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary written informed consent to participate in the study BCVA ETDRS letter score of 73 letters to 35 letters as measured by the ETDRS visual acuity chart in the study eye at screening 500 μm ≥ CST ≥ 325 μm in the study eye at screening HbA1c ≤ 11% at screening Exclusion Criteria: Any signs of proliferative diabetic retinopathy in the study eye History of rubeosis in the study eye Uncontrolled glaucoma in the study eye Aphakia or pseudophakia with AC-IOL in the study eye Active intraocular inflammation in the study eye Any current ocular condition for which visual acuity loss would not improve from resolution of macular edema in the study eye History of rhegmatogenous retinal detachment in the study eye Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision in the study eye History of the following therapies in the study eye History of vitrectomy surgery, submacular surgery, or other surgical intervention for DME Previous use of periocular or intraocular (sub-Tenon or IVT) corticosteroids Previous intraocular device implantation except PC-IOL Previous laser (any type) to the macular area Previous panretinal photocoagulation treatment Previous treatment with any IVT anti-VEGF drugs Previous use of Ozurdex® or Iluvien® implant Any current or history of endophthalmitis in either eye History of idiopathic or autoimmune-associated uveitis in either eye Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>KHK4951 High dose | Drug: KHK4951<br>* KHK4951 eye drop for 36 weeks until end of the trial<br>Drug: Aflibercept Injection<br>* Intravitreal injection (IVT) of aflibercept will be given as specified in the protocol<br>|
| Experimental: Arm B<br>KHK4951 Middle dose | Drug: KHK4951<br>* KHK4951 eye drop for 36 weeks until end of the trial<br>Drug: Aflibercept Injection<br>* Intravitreal injection (IVT) of aflibercept will be given as specified in the protocol<br>|
| Experimental: Arm C<br>KHK4951 Low dose | Drug: KHK4951<br>* KHK4951 eye drop for 36 weeks until end of the trial<br>Drug: Aflibercept Injection<br>* Intravitreal injection (IVT) of aflibercept will be given as specified in the protocol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of 15 or more letters in BCVA (Best corrected visual acuity) as measured by ETDRS visual acuity chart from baseline |  | For 36 weeks until the end of the trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of aflibercept IVT |  | For 36 weeks until the end of the trial | 
| Change from baseline in SHRM as measured by SD-OCT |  | 36 Weeks | 
| Change from baseline in retinal morphology as measured by SD-OCT |  | 36 Weeks | 
| Change from baseline in leakage as measured by FA |  | 36 Weeks |