NCT02592330

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
23

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Aug 2016

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 9, 2015

Completed
9 months until next milestone

First Posted

Study publicly available on registry

October 30, 2015

Completed
9 months until next milestone

Study Start

First participant enrolled

August 1, 2016

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2023

Completed
1.8 years until next milestone

Results Posted

Study results publicly available

January 15, 2025

Completed
Last Updated

January 15, 2025

Status Verified

January 1, 2025

Enrollment Period

6.7 years

First QC Date

February 9, 2015

Results QC Date

June 18, 2024

Last Update Submit

January 2, 2025

Conditions

Limbal Stem Cell Deficiency

Keywords

LSCD treatmentLimbal Stem Cell DeficiencyCALECCultivated Autologous Limbal Epithelial Cell TransplantationCorneal epithelial stem cellsCorneal scarringCorneal opacityChemical injury eyeThermal injury eyeAutologous stem cellEpithelial defectCorneal cloudinessOcular burnOcular injuryAutograftConjunctival Limbal AutograftLSCD researchChronic contact lens wearChronic keratoconjunctivitisCorneal conjunctivalizationCorneal fibrovascular pannusCorneal neovascularizationCorneal regenerationInfectious keratitisLimbal epithelial stem cell deficiencyOcular injury drug toxicityOcular surface disorderNeovascularization pannusNeurotrophic keratitisOcular surface InflammationEye injury ionizing radiationEye injury ultraviolet radiationCorneal pannusCorneal wound healingNeurotrophic keratopathyLSCD trialStem cell therapyEpithelial surface integrityRegrowing corneas

Outcome Measures

Primary Outcomes (2)

  • Primary Safety Events of Interest

    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%

    18 Months

  • Manufacturing Feasibility Measures

    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.

    18 Months

Secondary Outcomes (1)

  • Measure of Transplant Efficacy

    18 Months

Study Arms (1)

Cultivated Autologous Limbal Epithelial Cell (CALEC) graft

EXPERIMENTAL

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 graftBiological: Cultivation of Limbal epithelial cells into a graftProcedure: CALEC Transplant

Interventions

Biopsy to collect limbal epithelial stem cells that will be cultivated into a graftPROCEDURE

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.

Also known as: Cultivated Autologous Limbal Epithelial Cell (CALEC)
Cultivated Autologous Limbal Epithelial Cell (CALEC) graft
Cultivation of Limbal epithelial cells into a graftBIOLOGICAL

A graft is manufactured for transplant

Cultivated Autologous Limbal Epithelial Cell (CALEC) graft
CALEC TransplantPROCEDURE

Limbal epithelial cells are obtained from the healthy fellow eye and cultivated in a lab for later transplantation into the diseased eye.

Also known as: Conjunctival Limbal Autograft
Cultivated Autologous Limbal Epithelial Cell (CALEC) graft

Eligibility Criteria

Age18 Years - 89 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

Related Publications (2)

  • Yavuz Saricay L, Kaufman AR, Johns LK, Yin J, Samarakoon L, Ayala AR, Maguire M, Parekh M, Hernandez Rodriguez DE, Daley H, Dana R, Armant M, Ritz J, Jurkunas UV. Central Cornea Changes on Anterior Segment OCT and In Vivo Confocal Microscopy After Autologous Limbal Epithelial Cell Transplantation. Cornea. 2025 Mar 28. doi: 10.1097/ICO.0000000000003865. Online ahead of print.

    PMID: 40152603DERIVED

  • Jurkunas UV, Kaufman AR, Yin J, Ayala A, Maguire M, Samarakoon L, Johns LK, Parekh M, Li S, Gauthier A, Negre H, Shaw KL, Hernandez Rodriguez DE, Daley H, Dana R, Armant M, Ritz J. Cultivated autologous limbal epithelial cell (CALEC) transplantation for limbal tem cell deficiency: a phase I/II clinical trial of the first xenobiotic-free, serum-free, antibiotic-free manufacturing protocol developed in the US. Nat Commun. 2025 Mar 4;16(1):1607. doi: 10.1038/s41467-025-56461-1.

    PMID: 40038272DERIVED

MeSH Terms

Conditions

Limbal Stem Cell DeficiencyCorneal InjuriesCorneal OpacityEye InjuriesCorneal Neovascularization

Condition Hierarchy (Ancestors)

Corneal DiseasesEye DiseasesFacial InjuriesCraniocerebral TraumaTrauma, Nervous SystemNervous System DiseasesWounds and InjuriesNeovascularization, PathologicMetaplasiaPathologic ProcessesPathological Conditions, Signs and Symptoms

Results Point of Contact

Title
Michael Cheung, MS, CCRP (Clinical Research Project Manager)
Organization
Massachusetts Eye and Ear
mcheung0@meei.harvard.edu
617-573-6981

Study Officials

  • Ula Jurkunas, MD

    Massachusetts Eye and Ear Infirmary

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: All subjects will receive the study intervention, a stem cell graft cultivated from their own cells.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor, Harvard Medical School

Study Record Dates

First Submitted

February 9, 2015

First Posted

October 30, 2015

Study Start

August 1, 2016

Primary Completion

March 31, 2023

Study Completion

March 31, 2023

Last Updated

January 15, 2025

Results First Posted

January 15, 2025

Record last verified: 2025-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)