Stem Cell Therapy for Limbal Stem Cell Deficiency

Study Overview
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Brief Summary
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This phase I study will collect preliminary information on the activity and safety of cLSC. We will investigate the ability to manufacture and transplant cLSC onto the cornea successfully at the time of surgery (feasibility), and have cLSC begin to populate the ocular surface (efficacy) without serious adverse events (safety).

Detailed Description
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20 patients with severe to total Limbal Stem Cell Deficiency (LSCD) in one eye attributable to injury or ocular surgery. The first 5 eyes will receive the cLSCs to determine the feasibility and safety. Then the subsequent 15 eyes will be randomized into cLSC group and a scleral lens treatment (SCL) control group in a 2:1 ratio in blocks of 3 or 6 using a random number generator.

Official Title
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Safety and Feasibility of Cultivated Autologous Limbal Stem Cells (cLSC) for Limbal Stem Cell Deficiency

Conditions
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Limbal Stem-cell Deficiency

Intervention / Treatment
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* Biological: cLSC
* Device: Scleral contact lens (SCL)


Participation Criteria
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Eligibility Criteria
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Main inclusion Criteria: Male or female ≥18 years of age. Best corrected visual acuity in the affected eye of 20/200 or less. Documentation of a LSCD diagnosis and the central cornea is affected. Absence of lagophthalmos and eyelid abnormality Adequate forniceal depth is ≥ 5 mm. LSCD fails to resolve by surgical treatments of the ocular surface during the previous 6 months of screening visit. If the etiology of LSCD is due to chemical injury, a minimal interval of 1 year since the initial chemical injury is required. A Schirmer test result at 5 minute of ≥5 mm of wetting. Absence of active infectious keratitis in either eye at the Enrollment Visit. Have a life expectancy ≥ 2 years after enrollment. Main exclusion Criteria: Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data. Exposure keratopathy or lagophthalmos of the study eye. Persistent severe ocular surface inflammation and/or meibomian gland dysfunction Chemical injury occurred less than 12 months ago. Presence of ocular surface tumor. Uncontrolled diabetes with last hemoglobin A1C (HgA1C) >8.5. Presence of known allergies to any of the cLSC components. Current participation in another simultaneous medical investigation or trial. Unable to be compliant with or complete the requirements of the study.

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cultivated Limbal Stem-Cells (cLSC)<br>One dose of cultivated limbal stem-cells (cLSC), size between 7.6 to 15 mm in the average diameter. | Biological: cLSC<br>* Transplantation of cLSC<br>|
| Active Comparator: Scleral Contact Lens Device (SCL)<br>Scleral contact lens device (SCL) will be fitted to stabilize and improve ocular surface. | Device: Scleral contact lens (SCL)<br>* Scleral contact lens device (SCL) will be used to stabilize and improve ocular surface.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of cLSC Transplant pertaining to Infection and/or Corneal Perforation | Safety assessed by incidence of Serious Adverse Events (SAEs) directly related to cLSC: infection and/or corneal perforation. | 12 months for all participants | 
| Feasibility of cLSC Transplant pertaining to Manufacturing meeting Release Criteria | Feasibility assessed by successful manufacturing of cLSC from biopsy that meets release criteria. | 12 months for all participants | 
| Feasibility of cLSC Transplant pertaining to Manufacturing without Contamination | Feasibility assessed by successful cLSC manufacturing without contamination. | 12 months for all participants | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the Area of Corneal Epithelial Defect | Evaluate changes in the area of corneal epithelial defect (ED) or lack of ED. | At 6 months and 12 months in both cLSC and the control groups | 
| Changes in the Clinical Score | Evaluate changes in the clinical score determined by slit lamp examination using fluorescein staining and confocal imaging. | At 6 months and 12 months in both cLSC and the control groups |