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

Abstract

Purpose : 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. Mesenchymal Stromal Cells (MSCs) play an important role in tissue repair and maintenance and have been used as a cell-therapy in numerous clinical studies. The purpose of this study was to evaluate the safety and dosing of allogeneic bone marrow-derived MSCs for promoting corneal epithelial repair.

Methods : In the first cohort of our single center, Phase 1, 3 + 3 conventional cohort expansion dose-escalation study, participants with stage 2 or 3 non-healing corneal epithelial defects received a single subconjunctival injection of 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) MSCs along with their standard of care. Primary outcome measures included safety, defined as incidence of treatment emergent adverse events (TAEs) assessed at 28 days, and efficacy, defined as proportion of participants with epithelial defect closure assessed via slit lamp fluorescein staining exam.

Results : The initial cohort of n=3 participants were enrolled. At 28 days no TAEs occurred and all participants had improvement in size of corneal epithelial defects. Complete resolution was seen in one participant by 14 days, and between 28 and 56 days in another participant. The third participant, who is still being followed, had 80% improvement in epithelial defect size at 28 days.

Conclusions : These early results support the safety of locally delivered MSCs for non-healing corneal epithelial defects, while providing some signs of efficacy. Additional cohorts of this dose-escalation study, followed by further double masked, placebo controlled studies of larger size and longer duration are warranted in determining the efficacy of MSC as a treatment modality for corneal epithelial defects.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.