Safety and Pilot Efficacy of AKB-9778 in Subjects 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, pharmacokinetics, pharmacodynamics, and pilot efficacy of multiple ascending dose levels of AKB-9778 given as subcutaneous injections daily for 28 days in patients with diabetic macular edema (DME).

Official Title
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Phase 1b/2a Open Label, Multiple-Ascending Dose Cohort Study to Assess the Safety, Tolerability, Pilot Efficacy, Pharmacokinetics and Pharmacodynamic Effects of 28 Day Repeat Subcutaneous Doses of AKB-9778 in Subjects With Diabetic Macular Edema

Conditions
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Diabetic Macular Edema (DME)

Intervention / Treatment
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* Drug: Subcutaneous AKB-9778


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 determined to be primarily the result of DME in the study eye Definite Retinal thickening due to diffuse DME involving the center of the macula in the study eye Mean central subfield thickness of at least 325 µm by OCT in the study eye Early Treatment Diabetic Retinopathy Study (ETDRS) letter score BCVA ≤ 70 (20/40) in the study eye Exclusion Criteria: The following is an abbreviated list of exclusion criteria: Hemoglobin A1C (HbA1C) ≥ 11.5% History of any of the following in the study eye (however, the following are not exclusionary in the fellow eye): Panretinal scatter photocoagulation (PRP) or focal laser within 12 weeks prior to Screening Prior pars plana vitrectomy within 12 weeks prior to Screening Any ocular surgery within 12 weeks prior to Screening YAG capsulotomy within 7 days prior to Screening Prior intravitreal, subtenon, or periocular steroid therapy within 3 months prior to Screening or prior treatment with intravitreal anti-VEGF treatment within 1 month of Screening

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AKB-9778<br>Up to 4 dose levels of subcutaneous AKB-9778 will be evaluated. Doses will be administered daily for 28 days. | Drug: Subcutaneous AKB-9778<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (AEs). |  | 28 days | 
| Change from baseline in physical exams. |  | 28 days | 
| Change from baseline in vital signs. |  | 28 days | 
| Change from baseline in electrocardiograms (ECGs). |  | 28 days | 
| Change from baseline in opthalmic exams. |  | 28 days | 
| Change from baseline in clinical laboratory assay results. | Blood chemistry, hematology and urinalysis. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of AKB-9778 | Maximum plasma drug concentration (Cmax). Area under the plasma concentration-time curve (AUC). | Day 1 and Day 14 | 
| Change from baseline in optical tomography (OCT)-measured retinal thickness. |  | 28 days | 
| Change from baseline in best corrected visual acuity (BCVA). |  | 28 days |