Safety and tolerability of topical mesenchymal stromal cell secretome in persistent corneal epithelial disease-a phase 1b clinical trial.

BACKGROUND AIMS: To investigate the safety and tolerability of a topical allogeneic bone marrow-derived mesenchymal stromal cell (BM-MSC) secretome in chronic corneal epithelial disease. METHODS: A prospective single-center, uncontrolled, open-label phase 1b clinical trial was conducted.A dose escalation study design was used. Participants were patients with persistent corneal epithelial disease in the setting of neurotrophic keratitis and/or limbal stem cell deficiency.The first 3 participants were treated with topical BM-MSC secretome in 1 eye twice daily, the next 3 participants received the treatment 4 times a day, and the last 3 received it 6 times a day for 28 days. The primary outcomes were safety and the maximum tolerated dose (MTD) of the topical BM-MSC secretome. Ocular surface toxicity and other ocular or systemic treatment-emergent adverse events were assessed up to 90 days. Demonstration of safety on day 28 was required for each dosing frequency group before escalating to the next higher dose. RESULTS: A total of 9 participants were enrolled. No dose-limiting toxicities (DLTs) were observed in the 6 patients who received the BM-MSC secretome 2 or 4 times a day. Two of the 3 participants who were treated 6 times a day developed reversible DLTs, including a new corneal epithelial defect and increased central corneal staining with a consequent transient reduction in best-corrected visual acuity (BCVA). Potential signals of clinical efficacy were observed, particularly in the BCVA and corneal sensation in the majority of participants who completed the treatment. CONCLUSION: Topical BM-MSC secretome 2 or 4 times a day for 28 days was safe and well tolerated without signs of systemic or ocular toxicity in persistent corneal epithelial disease.