Phase I Study on the Safety of Locally Delivered Allogeneic Mesenchymal Stem Cells for Promoting Corneal Repair

Abstract

Purpose : To evaluate the safety and dosing of allogeneic, bone marrow-derived Mesenchymal Stem Cells (MSCs) for promoting corneal epithelial repair. Non-penetrating injuries to the cornea and ocular surface, including non-healing persistent epithelial defects, are a significant cause of combat-related visual loss and morbidity.

Methods : This was a non-randomized, single center, 3+3 conventional cohort expansion dose-escalation study of adult patients with stage 2 or 3 non-healing corneal epithelial defects, who were treated with freshly thawed bone marrow-derived MSCs. Participants met eligibility criteria for clinical trial ID #NCT04626583 and agreed to participate in an IRB-approved protocol for Investigational New Drug #18400 (FDA/CBER). MSCs were produced at the University of Illinois Hospital Clinical Stem Cell Laboratory following Good Manufacturing Practice protocols and were stored in cryogenic conditions. Patients received a single subconjunctival injection of 1.0 x 10⁶ (50ul) or 3.0 x 10⁶ (150ul) MSCs along with their standard of care. Primary outcome measures included safety, defined as the incidence of treatment-related adverse events (TAEs) assessed at 28 days, and efficacy, defined as the proportion of participants with epithelial defect closure assessed via slit lamp fluorescein staining exam.

Results : To date, 6 participants have completed the study. At 28 days, no TAEs occurred to any of the patients, with 4 participants exhibiting significant reduction in the size of their corneal epithelial defects. Complete resolution was seen in 1 participant by 7 days, in 2 other participants between 28 and 90 days, and in 1 participant within two weeks of starting antivirals at 90 days. The remaining 2 patients, both in the medium dose cohort, had no change in defect size in response to MSC therapy.

Conclusions : These results support the safety of locally delivered MSCs for non-healing corneal epithelial defects, while providing some signs of efficacy, with the low dose group demonstrating a better response than the medium dose group in this limited sample. The third cohort, in which patients receive two subconjunctival injections of 3.0 x 10⁶ (150ul) MSCs, is currently ongoing. Further double-masked, placebo-controlled studies of larger size and longer duration are warranted to determine the efficacy of MSCs as a treatment modality for corneal epithelial defects.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.