Safety of Topical Mesenchymal Stromal Cell Secretome for Ocular Surface Disease

Study Overview
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Brief Summary
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This study is a longitudinal assessment using a classic dose-escalation study design to assess the safety and maximal tolerated dose (MTD) of topical MSC Secretome eye drops. The study will be conducted at Illinois Eye and Ear Infirmary located at University of Illinois at Chicago. The study will use anterior segment Optical Coherence Tomography (OCT)/Scheimpflug Imaging, esthesiometry, and visual analogue scale (VAS) to assess treatment tolerability.

Detailed Description
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The Safety of Topical Mesenchymal Stromal Cell Secretome for Ocular Surface Disease study is designed to evaluate the safety and maximal tolerated dose (MTD) of topical MSC Secretome eye drops in patients with chronic ocular surface disease through a dose-escalation study under a 28-day topical application protocol, and also obtain a preliminary observation on the following: Incidence of treatment emergent adverse events (TEAE) assessed at 28 days following treatment initiation Proportion of patients with improved corneal epithelial barrier at 28 days compared to baseline Final visual acuity, corneal epithelial thickness, corneal stromal haze, corneal sensation, and treatment tolerability The objective is to determine the dose of MSC Secretome through a first-in-human study through a dose-escalation strategy targeting a toxicity rate of 33% or less.

Official Title
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Safety of Topical Mesenchymal Stromal Cell Secretome for Ocular Surface Disease

Conditions
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Cornea, Mesenchymal Stromal Cells, Corneal Defect, Corneal Epithelium Defect

Intervention / Treatment
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* Biological: MSC Secretome Eye Drops


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years of age or older Chronic corneal epithelial disease with fluorescein staining score ≥ 6 by NEI grading scale Reduced corneal sensation (≤ 4 cm measured by Cochet Bonnet esthesiometry) in at least one corneal quadrant A stable ocular surface with no objective clinical evidence of significant (> 50%) improvement/worsening of the epithelial disease in the last 30 days Epithelial disease refractory to conventional non-surgical treatments (e.g., preservative-free artificial tears, gels or ointments; discontinuation of preserved topical drops; anti-inflammatory therapy) Exclusion Criteria: Any active or suspected ocular infection (bacterial, viral, fungal or protozoal). Evidence of corneal ulceration with stromal loss > 10% Presence of an epithelial defect ≥1.0 mm in the largest diameter in the affected eye Presence of any size epithelial defect that has been persistent for more than 30 days Patients unable to discontinue or intermittently remove therapeutic contact lens in the study eye (to apply drops) during the 4-week study period History of any ocular surgery (including laser or refractive surgical procedures) in the affected eye within the 3 months prior to study enrollment History of chemical injury within the last 6 months prior to study enrollment Known hypersensitivity to one of the components of the study or procedural medications (e.g.,fluorescein) History of drug, medication or alcohol abuse or addiction Use of any investigational agent within 4 weeks of screening visit History of previous enrollment in the MSC Secretome Study at a lower dose Participation in another clinical study at the same time as the present study Participants who are pregnant at the time of study enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: A longitudinal assessment using a classic dose-escalation study design to evaluate the safety and maximal tolerated dose of topical MSC Secretome eye drops
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low dose of allogenic MSC drops<br>Escalating doses of allogenic MSC eye drops will be assigned at the lowest dose level. | Biological: MSC Secretome Eye Drops<br>* MSC Secretome eye drop will be dispensed.<br>|
| Active Comparator: Medium dose of allogenic MSC drops<br>Escalating doses of allogenic MSC eye drops will be assigned at the medium dose level. | Biological: MSC Secretome Eye Drops<br>* MSC Secretome eye drop will be dispensed.<br>|
| Active Comparator: High dose of allogenic MSC drops<br>Escalating doses of allogenic MSC eye drops will be assigned at the high dose level. | Biological: MSC Secretome Eye Drops<br>* MSC Secretome eye drop will be dispensed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epithelial Status Assessment | The primary outcome measure is improved corneal epithelial barrier function at DAY #28assessed by viewing the cornea under slit lamp examination after instillation of sodium fluorescein, assessing the change from baseline in corneal fluorescein staining score. The presence/absence of an epithelial defect on DAY #28 will also be recorded. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Acuity | Best-corrected distance visual acuity will be measured using standard ETDRS protocols. | Baseline, Days 7, 14, 28, 56, 90 | 
| Corneal Epithelial thickness | Corneal epithelial thickness measured by anterior segment OCT imaging (Cirrus 6000, Pachymetry, a-scans and b-scans) will assess the treatment effect on thickness on DAY #28 and compared relative to baseline. | Baseline, Days 14, 28, 56, 90 | 
| Corneal Scarring / Haze | Corneal scarring/haze will be assessed via anterior segment OCT imaging (Cirrus 6000; HD cornea, a-scans) to assess the treatment effect on DAY #28 relative to baseline(Images analysis done by Image-J/Metamorph) | Baseline, Days 14, 28, 56, 90 | 
| Tolerability of MSC secretome drops | Drop discomfort will be measured at DAYS #7, #14, and #28 using a visual analogue scale (VAS; range 0 -100), where 0 represents no discomfort and 100 the worst discomfort. | Baseline, Days 7, 14, 28, 56, 90 | 
| Durability of Corneal Epithelial Status Improvement | Durability of the improved corneal epithelial barrier function/integrity will be assessed an outcome measure at DAY #56 and DAY #90. Participants with improved corneal epithelial barrier function/integrity to DAY #28 will be assessed at each subsequent follow-up visits (e.g., DAYS #56, #90) to assess persistence of the healing response. | Baseline, Days 7, 14, 28, 56, 90 | 
| Time to Improvement of Corneal Epithelial Barrier | The time required for an improved epithelial barrier function will be assessed at each visit throughout the trial. | Baseline, Days 7, 14, 28, 56, 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal Stromal Cells, Corneal Defect, Corneal Epithelium Defect