Limbal Stem Cell Deficiency (LSCD) Treatment With Cultivated Stem Cell (CALEC) Graft

Study Overview
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Brief Summary
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The main aim of the study is to determine the safety and feasibility of a cultivated autologous limbal epithelial cell (CALEC) transplantation in the treatment of limbal stem cell deficiency.

Detailed Description
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This is an open label, single center study to assess safety, feasibility, and efficacy of Cultivated Autologous Limbal Epithelial Cell (CALEC) grafts in 17 patients with unilateral limbal stem cell deficiency (LSCD). Participants will have a corneal biopsy in their non-diseased eye, which will provide cells for the creation of the CALEC graft. The CALEC will be made at the Good Manufacturing Practice (GMP) Laboratory, Dana Farber Cancer Institute and transported to Mass. Eye and Ear Infirmary for application to the participant's diseased eye during their standard corneal reconstruction procedure. Subjects will be monitored up to month 18 post-transplant to assess for any delayed adverse events of the product (CALEC) or procedure as well as assessment of the durability of the transplant.

Official Title
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Safety and Feasibility of Cultivated Autologous Limbal Epithelial Cell Transplantation in the Treatment of Limbal Stem Cell Deficiency (LSCD)

Conditions
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Limbal Stem Cell Deficiency

Intervention / Treatment
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* Procedure: Biopsy to collect limbal epithelial stem cells that will be cultivated into a graft
* Biological: Cultivation of Limbal epithelial cells into a graft
* Procedure: CALEC Transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants age 18 to <90 years old at time of enrollment Ability of a subject or guardian/legal representative to provide written informed consent and to comply with study assessments for the full duration of the study. Patients with unilateral limbal stem cell deficiency (LSCD) as determined by conjunctivalization of the cornea defined by fibrovascular pannus more than 2 mm from the limbus for greater than or equal to 6 clock hours. Additional optional criteria: Lack of limbal palisades of Vogt for greater than or equal to 9 clock hours Goblet cell presence as defined by impression cytologic criteria Exclusion Criteria: Corneal or ocular surface infection within 30 days prior to study entry or CALEC transplantation Ocular surface malignancy Uncontrolled diabetes with most recent HgA1c greater than 8.5% Renal Failure with eGFR below 60 mL/min per 1.73 m2 Aspartate aminotransferase and alanine aminotransferase levels greater than 3 times institutional upper limit of normal Total bilirubin greater than 2 times institutional upper limit of normal (except patients with known Gilbert's syndrome) Platelet levels less than 100,000 or greater than 450,000 per microliter Hemoglobin levels of less than 11.0 g/dL in men or less than 10.0 g/dL in women Prothrombin time greater than 16 seconds and activated partial thromboplastin time greater than 35 seconds in patients not taking warfarin and an international normalized ratio greater than 3 in patients taking warfarin Inability to tolerate monitored anesthesia HIV infection or AIDS Active Hepatitis B or C Pregnancy (positive test) or lactation Participation in another simultaneous medical investigation or trial Severe cicatricial eye disease Severe dry eye disease as determined by Schirmer's test less than 1mm in at least one eye. Any medical, psychiatric, debilitating disease/disorder or social condition that in the judgment of the investigator would interfere with or serve as a contraindication to adherence to the study protocol or ability to give informed consent. Signs of current infection, including fever and current treatment with antibiotics. History of allo-limbal transplantation Presence of allergy to the CALEC graft or any of the chemical components within its formulation. Exclusion Based on Donor Eye: Conjunctivalization of the cornea defined by fibrovascular pannus more than 2 mm from the limbus for greater than or equal to 3 clock hours Lack of limbal palisades of Vogt for greater than or equal to 3 clock hours History of allo-limbal transplantation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 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
Intervention Model: Single Group Assignment
Interventional Model Description: All subjects will receive the study intervention, a stem cell graft cultivated from their own cells.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cultivated Autologous Limbal Epithelial Cell (CALEC) graft<br>Participants will have a corneal biopsy in their non-diseased eye, which will provide cells for the creation of the CALEC graft. The CALEC will be made at the Good Manufacturing Practice (GMP) Laboratory, Dana Farber Cancer Institute and transported to Mass. Eye and Ear Infirmary for application to the participant's diseased eye during their standard corneal reconstruction procedure. | Procedure: Biopsy to collect limbal epithelial stem cells that will be cultivated into a graft<br>* Cultivated autologous limbal epithelial cell (CALEC) therapy utilizes a bio-engineered composite of ex vivo expanded autologous corneal epithelial cells and an FDA-approved amniotic membrane (AmnioGraft®, Bio-Tissue, Inc.) to reconstruct the ocular surface. A small biopsy (2-3 mm2) from the patient's contralateral eye serves as a source epithelial (stem) cells that are expanded on the amniotic membrane in culture and the resulting product is surgically transplanted onto the cornea after excision of the fibrovascular pannus.<br>* Other names: Cultivated Autologous Limbal Epithelial Cell (CALEC);Biological: Cultivation of Limbal epithelial cells into a graft<br>* A graft is manufactured for transplant<br>Procedure: CALEC Transplant<br>* Limbal epithelial cells are obtained from the healthy fellow eye and cultivated in a lab for later transplantation into the diseased eye.<br>* Other names: Conjunctival Limbal Autograft;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - The occurrence of ocular infection | Measurement of the incidence of ocular infection | 2 years | 
| Safety - The occurrence of corneal perforation. | Measurement of the incidence of corneal perforation. | 2 years | 
| Safety - The occurrence of graft detachment ≥ 50%. | Measurement of the incidence of graft detachment ≥ 50%. | 2 years | 
| Safety - The occurrence adverse events and their relationship to the study intervention | Measurement of the number and severity of adverse events | 2 years | 
| Feasibility - obtaining cell growth and maintaining cell viability | Measurement of number of cells in graft at intervals to establish feasibility of manufacturing CALEC for corneal transplantation | 2 years | 
| Feasibility - avoiding culture contamination | Measurement of the incidence of culture contamination. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - Improvement in corneal surface Integrity | Measurement of decreases in frank epithelial defect surface area (success is improvement from baseline to post-op of >75%), and decreases in surface staining (NEI grading scale). Success is improvement from baseline to post-op of >50%. | 2 years | 
| Efficacy - Decrease in neovascularization | Measurement of decrease in neovascular area. Success is decrease in neovascularization from baseline to post-op of >25% | 2 years | 
| Efficacy- Decrease in subject symptoms | Measurement of change from baseline to post-op in Ocular Surface Disease Index (OSDI) and Symptom Assessment iN Dry Eye (SANDE) scores | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LSCD treatment, Limbal Stem Cell Deficiency, CALEC, Cultivated Autologous Limbal Epithelial Cell Transplantation, Corneal epithelial stem cells, Corneal scarring, Corneal opacity, Chemical injury eye, Thermal injury eye, Autologous stem cell, Epithelial defect, Corneal cloudiness, Ocular burn, Ocular injury, Autograft, Conjunctival Limbal Autograft, LSCD research, Chronic contact lens wear, Chronic keratoconjunctivitis, Corneal conjunctivalization, Corneal fibrovascular pannus, Corneal neovascularization, Corneal regeneration, Infectious keratitis, Limbal epithelial stem cell deficiency, Ocular injury drug toxicity, Ocular surface disorder, Neovascularization pannus, Neurotrophic keratitis, Ocular surface Inflammation, Eye injury ionizing radiation, Eye injury ultraviolet radiation, Corneal pannus, Corneal wound healing, Neurotrophic keratopathy, LSCD trial, Stem cell therapy, Epithelial surface integrity, Regrowing corneas