MSC Secretome: Safety of Topical Mesenchymal Stromal Cell Secretome for Ocular Surface Disease
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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Early Phase 1 |
Detailed Description
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:
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Incidence of treatment emergent adverse events (TEAE) assessed at 28 days following treatment initiation
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Proportion of patients with improved corneal epithelial barrier at 28 days compared to baseline
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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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Active Comparator: Low dose of allogenic MSC drops Escalating doses of allogenic MSC eye drops will be assigned at the lowest dose level. |
Biological: MSC Secretome Eye Drops
MSC Secretome eye drop will be dispensed.
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Active Comparator: Medium dose of allogenic MSC drops Escalating doses of allogenic MSC eye drops will be assigned at the medium dose level. |
Biological: MSC Secretome Eye Drops
MSC Secretome eye drop will be dispensed.
|
Active Comparator: High dose of allogenic MSC drops Escalating doses of allogenic MSC eye drops will be assigned at the high dose level. |
Biological: MSC Secretome Eye Drops
MSC Secretome eye drop will be dispensed.
|
Outcome Measures
Primary Outcome Measures
- Epithelial Status Assessment [Day 28]
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.
Secondary Outcome Measures
- Visual Acuity [Baseline, Days 7, 14, 28, 56, 90]
Best-corrected distance visual acuity will be measured using standard ETDRS protocols.
- Corneal Epithelial thickness [Baseline, Days 14, 28, 56, 90]
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.
- Corneal Scarring / Haze [Baseline, Days 14, 28, 56, 90]
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)
- Tolerability of MSC secretome drops [Baseline, Days 7, 14, 28, 56, 90]
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.
- Durability of Corneal Epithelial Status Improvement [Baseline, Days 7, 14, 28, 56, 90]
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.
- Time to Improvement of Corneal Epithelial Barrier [Baseline, Days 7, 14, 28, 56, 90]
The time required for an improved epithelial barrier function will be assessed at each visit throughout the trial.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients 18 years of age or older
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Chronic corneal epithelial disease with fluorescein staining score ≥ 6 by NEI grading scale
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Reduced corneal sensation (≤ 4 cm measured by Cochet Bonnet esthesiometry) in at least one corneal quadrant
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A stable ocular surface with no objective clinical evidence of significant (> 50%) improvement/worsening of the epithelial disease in the last 30 days
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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:
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Any active or suspected ocular infection (bacterial, viral, fungal or protozoal).
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Evidence of corneal ulceration with stromal loss > 10%
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Presence of an epithelial defect ≥1.0 mm in the largest diameter in the affected eye
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Presence of any size epithelial defect that has been persistent for more than 30 days
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Patients unable to discontinue or intermittently remove therapeutic contact lens in the study eye (to apply drops) during the 4-week study period
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History of any ocular surgery (including laser or refractive surgical procedures) in the affected eye within the 3 months prior to study enrollment
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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)
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History of drug, medication or alcohol abuse or addiction
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Use of any investigational agent within 4 weeks of screening visit
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History of previous enrollment in the MSC Secretome Study at a lower dose
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Participation in another clinical study at the same time as the present study
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Participants who are pregnant at the time of study enrollment
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- University of Illinois at Chicago
- National Institutes of Health (NIH)
- National Eye Institute (NEI)
Investigators
- Principal Investigator: Ali R Djalilian, MD, University of Illinois at Chicago
- Principal Investigator: Charlotte E Joslin, OD, PhD, University of Illinois at Chicago
- Principal Investigator: Elmer Y Tu, MD, University of Illinois at Chicago
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
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- Prockop DJ, Oh JY. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol Ther. 2012 Jan;20(1):14-20. doi: 10.1038/mt.2011.211. Epub 2011 Oct 18. Review.
- Roddy GW, Oh JY, Lee RH, Bartosh TJ, Ylostalo J, Coble K, Rosa RH Jr, Prockop DJ. Action at a distance: systemically administered adult stem/progenitor cells (MSCs) reduce inflammatory damage to the cornea without engraftment and primarily by secretion of TNF-α stimulated gene/protein 6. Stem Cells. 2011 Oct;29(10):1572-9. doi: 10.1002/stem.708.
- Samaeekia R, Rabiee B, Putra I, Shen X, Park YJ, Hematti P, Eslani M, Djalilian AR. Effect of Human Corneal Mesenchymal Stromal Cell-derived Exosomes on Corneal Epithelial Wound Healing. Invest Ophthalmol Vis Sci. 2018 Oct 1;59(12):5194-5200. doi: 10.1167/iovs.18-24803.
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- Yun YI, Park SY, Lee HJ, Ko JH, Kim MK, Wee WR, Reger RL, Gregory CA, Choi H, Fulcher SF, Prockop DJ, Oh JY. Comparison of the anti-inflammatory effects of induced pluripotent stem cell-derived and bone marrow-derived mesenchymal stromal cells in a murine model of corneal injury. Cytotherapy. 2017 Jan;19(1):28-35. doi: 10.1016/j.jcyt.2016.10.007. Epub 2016 Nov 10.
- 2021-0754
- 1UG3EY031809-01