The TIME-2 Study: A Phase 2 Study of AKB-9778, a Novel Tie-2 Activator, 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 the safety and efficacy of AKB-9778 administered as daily subcutaneous injections with and without monthly intravitreal injections of ranibizumab for 3 months in patients with diabetic macular edema.

Official Title
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A Phase 2, Randomized, Active-Controlled, Double-Masked, Multi-Center Study to Assess the Safety and Efficacy of Daily Subcutaneous AKB-9778 Administered for 3 Months, as Monotherapy or Adjunctive to Ranibizumab, in Subjects With Diabetic Macular Edema

Conditions
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Diabetic Macular Edema (DME)

Intervention / Treatment
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* Drug: AKB-9778
* Drug: ranibizumab
* Drug: Placebo
* Drug: Sham


Participation Criteria
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Eligibility Criteria
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The following is an abbreviated list of inclusion criteria: Adults between 18 to 80 years of age, inclusive Diagnosis of diabetes mellitus (type 1 or type 2) Decrease in vision in the study eye determined to be primarily the result of DME Definite retinal thickening due to diffuse DME involving the central macula in the study eye Central subfield thickness of at least 325 µm by sdOCT with presence of intraretinal fluid in the study eye ETDRS BCVA letter score ≤ 76 and ≥ 24 in the study eye The following is an abbreviated list of exclusion criteria: Hemoglobin A1C (HbA1C) ≥ 12.0% at Screening History of non infectious uveitis Decrease in visual acuity due to causes other than DME in the study eye History of any of the following in the study eye (however, the following are not exclusionary in the fellow eye): Prior pars plana vitrectomy Any ocular surgery within 3 months prior to Day 1 YAG capsulotomy within 3 months prior to Day 1 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 Prior intravitreal, subtenon, or periocular steroid therapy within 3 months prior to Day 1 Prior treatment with intravitreal anti-vascular endothelial growth factor (VEGF) treatment within 8 weeks prior to Day 1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: AKB-9778 15 mg BID monotherapy<br>Subcutaneous AKB-9778 15 mg BID (total daily dose of 30 mg/day) plus monthly sham intravitreal injection for 3 months. | Drug: AKB-9778<br> <br> Drug: Sham<br> <br> |
| Experimental: AKB-9778 15 mg BID + ranibizumab 0.3 mg<br>Subcutaneous AKB-9778 15 mg BID (total daily dose of 30 mg/day) plus ranibizumab 0.3 mg monthly intravitreal injection for 3 months. | Drug: AKB-9778<br> <br> Drug: ranibizumab<br> <br> * Other names: Lucentis;|
| Active Comparator: ranibizumab 0.3 mg monotherapy<br>Placebo subcutaneous injection (BID) plus ranibizumab 0.3 mg monthly intravitreal injection for 3 months. | Drug: ranibizumab<br> <br> * Other names: Lucentis;Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in spectral domain optical coherence tomography (sdOCT)-measured central subfield thickness (CST) |  | Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) |  | Month 3 |