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

Limbal Stem Cell Deficiency Clinical Trial

— CALEC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02592330
• Other study ID #: 14-124H
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 1, 2016
• Est. completion date: March 31, 2023

Study information

• Verified date: December 2023
• Source: Massachusetts Eye and Ear Infirmary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: March 31, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

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

Related Conditions & MeSH terms

• Limbal Stem Cell Deficiency

Intervention

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.

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.

Locations

Country	Name	City	State
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts Eye and Ear Infirmary	Dana-Farber Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety - The occurrence of ocular infection	Measurement of the incidence of ocular infection	2 years
Primary	Safety - The occurrence of corneal perforation.	Measurement of the incidence of corneal perforation.	2 years
Primary	Safety - The occurrence of graft detachment = 50%.	Measurement of the incidence of graft detachment = 50%.	2 years
Primary	Safety - The occurrence adverse events and their relationship to the study intervention	Measurement of the number and severity of adverse events	2 years
Primary	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
Primary	Feasibility - avoiding culture contamination	Measurement of the incidence of culture contamination.	2 years
Secondary	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
Secondary	Efficacy - Decrease in neovascularization	Measurement of decrease in neovascular area. Success is decrease in neovascularization from baseline to post-op of >25%	2 years
Secondary	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