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Pravin U. Dugel, Arshad M. Khanani, Brian B. Berger, Sunil Patel, Mitchell Fineman, Glenn J. Jaffe, Petra Kozma-Wiebe, Jeffrey Heier; Phase 1 Dose-Escalation Study of Plasma Kallikrein Inhibitor THR-149 for the Treatment of Diabetic Macular Edema. Trans. Vis. Sci. Tech. 2021;10(14):28. doi: https://doi.org/10.1167/tvst.10.14.28.
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The purpose of this study was to evaluate the safety and preliminary efficacy of a single intravitreal injection of 3 dose levels of THR-149 in adults with center-involved diabetic macular edema (DME).
A phase 1, open-label, multicenter 3 + 3 dose-esclation study with 3-month follow-up. The primary endpoint was the incidence of dose-limiting toxicities (DLTs) up to and including the Day 14 visit. Additional key endpoints included the incidence of (serious) adverse events ([S]AEs), mean change from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST), and additional imaging parameters on widefield fluorescein angiography and optical coherence tomography (OCT) angiography.
Twelve subjects were treated: 3 subjects received THR-149 0.005 mg, 3 received 0.022 mg and 6 received 0.13 mg. Baseline ocular characteristics were balanced between subjects at each dose level. There were no DLTs or ocular SAEs, and all subjects completed the study. Six subjects experienced a total of 10 AEs in the study eye; 1 case of mild anterior chamber inflammation was deemed related to THR-149 and/or the injection procedure. Mean change from Baseline in BCVA was +7.5 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters on Day 14, and +6.4 ETDRS letters by Month 3. CST was variable, and mean CST change from baseline was +30.0 µm at Month 3. There were no clinically meaningful changes in imaging parameters.
THR-149 was safe and well tolerated; preliminary efficacy in terms of BCVA improvement was observed.
This work bridges the gap between basic research and clinical care by providing first in human safety and preliminary efficacy data, supporting the further investigation of THR-149 as a potential treatment for DME.
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