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

Phase 1

Completed

Conditions: Limbal Stem Cell Deficiency

Interventions: 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

Registration Number: NCT02592330

Lead Sponsor: Massachusetts Eye and Ear Infirmary

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 23

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cultivated Autologous Limbal Epithelial Cell (CALEC) graft	Cultivation of Limbal epithelial cells into a graft	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.
Cultivated Autologous Limbal Epithelial Cell (CALEC) graft	Biopsy to collect limbal epithelial stem cells that will be cultivated into a graft	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.
Cultivated Autologous Limbal Epithelial Cell (CALEC) graft	CALEC Transplant	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.

Primary Outcome Measures

Name	Time	Method
Primary Safety Events of Interest	18 Months	The occurrence of the following adverse events at any time during the 18 months of follow-up in the recipient eye will serve as the primary safety events of interest. 1. Ocular Infection (defined as endophthalmitis or microbial keratitis \[bacterial, fungal, parasitic\]: 2. Corneal Perforation 3. Graft Detachment ≥50%
Manufacturing Feasibility Measures	18 Months	Each biopsy attempt will be classified as a "feasibility success" if it produced at least one construct that met all of the Quality Control (QC) release criteria. Manufacturing feasibility will be evaluate on a biopsy level (denominator is the total number of biopsies).The number and percentage of biopsy attempts resulting in a feasibility success will be calculated.

Secondary Outcome Measures

Name	Time	Method
Measure of Transplant Efficacy	18 Months	The primary efficacy outcome will be a binary "Complete Success" of the graft defined as improvement in corneal surface integrity