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

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

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.

Study Overview

• Status: Completed
• Conditions: Limbal Stem Cell Deficiency
• Intervention / Treatment: 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

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts Eye and Ear Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cultivated Autologous Limbal Epithelial Cell (CALEC) 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.

Procedure: Biopsy to collect limbal epithelial stem cells that will be cultivated into a graft; 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.; Other Names: Cultivated Autologous Limbal Epithelial Cell (CALEC); Biological: Cultivation of Limbal epithelial cells into a graft; A graft is manufactured for transplant; Procedure: CALEC Transplant; Limbal epithelial cells are obtained from the healthy fellow eye and cultivated in a lab for later transplantation into the diseased eye.; Other Names: Conjunctival Limbal Autograft

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts Eye and Ear Infirmary
• Collaborators: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Ula Jurkunas, MD, Massachusetts Eye and Ear Infirmary

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: February 9, 2015
• First Submitted That Met QC Criteria: October 29, 2015
• First Posted (Estimated): October 30, 2015

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Corneal wound healing; Autograft; Corneal neovascularization; Limbal Stem Cell Deficiency; Stem cell therapy; LSCD treatment; 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; Conjunctival Limbal Autograft; LSCD research; Chronic contact lens wear; Chronic keratoconjunctivitis; Corneal conjunctivalization; Corneal fibrovascular pannus; Corneal regeneration; Ocular injury drug toxicity; Ocular surface disorder; Neovascularization pannus; Neurotrophic keratitis; Eye injury ionizing radiation; Eye injury ultraviolet radiation; Corneal pannus; Neurotrophic keratopathy; LSCD trial; Epithelial surface integrity; Regrowing corneas; Infectious keratitis; Ocular burn; Ocular injury; Limbal epithelial stem cell deficiency; Ocular surface Inflammation
• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Limbal Stem Cell Deficiency
• Other Study ID Numbers: 14-124H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO