Evaluation of Tonabersat for DME

A Phase 2 Evaluation of Tonabersat for Diabetic Macular Edema (Protocol AN)

This randomized clinical trial will evaluate the effect of tonabersat compared with placebo on central subfield thickness (CST) in eyes with center-involved diabetic macular edema (CI-DME) and good visual acuity.

The primary objective is to assess the effects of tonabersat, an orally administered Connexin43 hemichannel inhibitor, on central subfield thickness (mean change) compared with placebo in eyes with CI-DME and good visual acuity at 6 months.

Exploratory objectives will evaluate biomarkers of kidney function for potential benefit. Furthermore, this phase 2 study is being conducted to determine whether the conduct of a phase 3 trial has merit and provide information on outcome measures needed to design a phase 3 trial.

Key Inclusion Criteria

1. Adults with type 1 or 2 diabetes mellitus

2. At least one eye with:

   • Best corrected E-ETDRS visual acuity letter score ≥ 74 (i.e., 20/32 or better)

   • Ophthalmoscopic evidence of center-involved DME in study eye confirmed by central subfield thickness on spectral domain OCT

   • Zeiss Cirrus: ≥ 290 µm in females, ≥ 305 µm in males

   • Heidelberg Spectralis: ≥ 305 µm in females, ≥ 320 µm in males

     • Recruitment will be monitored with a goal to have equal proportions in the following categories above the CI-DME thresholds: <75 μm, 75 μm to <175 μm, ≥175 μm

3. Media clarity, pupillary dilation, and study participant cooperation sufficient for adequate OCT

Key Exclusion Criteria

• Macular edema is considered to be due to a cause other than DME
• Major ocular surgery within prior 4 months, or anticipated after randomization
• History of focal/grid laser or other ocular surgical, intravitreal, or peribulbar treatment for DR or DME within prior 1 year, and no more than 4 anti-VEGF injections within prior 3 years
• Anticipated need to treat DME or DR during the first 6 months, or anticipated need for cataract surgery during study period
• Any history of vitrectomy
• Systemic anti-VEGF or pro-VEGF treatment within 12 months prior to randomization
• History of chronic renal failure requiring dialysis or kidney transplant
• History of moderate to severe hepatic impairment, including known liver function test (LFT) values > 3x's the upper limit of normal