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

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ClinicalTrials.gov Identifier: NCT02592330
Recruitment Status : Recruiting
First Posted : October 30, 2015
Last Update Posted : January 29, 2020
Sponsor:
Collaborator:
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Ula Jurkunas, MD, 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.

Condition or disease Intervention/treatment Phase
Limbal Stem Cell Deficiency 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 Procedure: CLAU Phase 1 Phase 2

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 24 patients with unilateral limbal stem cell deficiency (LSCD). The first 3 participants enrolled will receive the study treatment, CALEC, to assess for safety and feasibility. Subjects 4-24 will be randomized to either the study treatment, CALEC, or to the standard treatment for LSCD, which is conjunctival limbal autograft (CLAU) in a 2:1 ratio.

Participants receiving the study intervention 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 randomized to the standard treatment arm will undergo CLAU surgery, with the biopsy performed at the time of surgery. Investigators, study personnel, and subjects will be aware of the study assignment, given the different procedures required for each, during and after surgery. Subjects will be monitored up to month 24 to assess for any delayed adverse events of the product (CALEC) or procedure as well as assessment of the durability of the transplant.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Feasibility of Cultivated Autologous Limbal Epithelial Cell Transplantation in the Treatment of Limbal Stem Cell Deficiency (LSCD)
Actual Study Start Date : August 1, 2016
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2021

Arm Intervention/treatment
Experimental: Cultivated Autologous Limbal Epithelial Cell (CALEC) graft
The first three subjects enrolled into the study will automatically receive CALEC. Subjects 4-27 will be randomized to either the study treatment, CALEC, or to the standard treatment for LSCD, which is conjunctival limbal autograft (CLAU) in a 2:1 ratio. Participants receiving CALEC 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 Name: 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 Name: Conjunctival Limbal Autograft

Active Comparator: Conjunctival Limbal Autograft (CLAU )
Subjects 4-27 will be randomized to either the study treatment, CALEC, or to the standard treatment for LSCD, which is conjunctival limbal autograft (CLAU) in a 2:1 ratio. Subjects randomized to the standard treatment arm will undergo CLAU surgery, with the biopsy performed at the time of surgery.
Procedure: CLAU
Tissue is obtained from the healthy fellow eye (a limbal autograft) and immediately transplanted to recipient eye to provide a new source of epithelium for a diseased ocular surface after the removal of the recipient's scarred and diseased epithelium.




Primary Outcome Measures :
  1. Safety - The occurrence of ocular infection [ Time Frame: 2 years ]
    Measurement of the incidence of ocular infection

  2. Safety - The occurrence of corneal perforation. [ Time Frame: 2 years ]
    Measurement of the incidence of corneal perforation.

  3. Safety - The occurrence of graft detachment ≥ 50%. [ Time Frame: 2 years ]
    Measurement of the incidence of graft detachment ≥ 50%.

  4. Safety - The occurrence adverse events and their relationship to the study intervention [ Time Frame: 2 years ]
    Measurement of the number and severity of adverse events

  5. Feasibility - obtaining cell growth and maintaining cell viability [ Time Frame: 2 years ]
    Measurement of number of cells in graft at intervals to establish feasibility of manufacturing CALEC for corneal transplantation

  6. Feasibility - avoiding culture contamination [ Time Frame: 2 years ]
    Measurement of the incidence of culture contamination.


Secondary Outcome Measures :
  1. Efficacy - Improvement in corneal surface Integrity [ Time Frame: 2 years ]
    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. Efficacy - Decrease in neovascularization [ Time Frame: 2 years ]
    Measurement of decrease in neovascular area. Success is decrease in neovascularization from baseline to post-op of >25%

  3. Efficacy- Decrease in subject symptoms [ Time Frame: 2 years ]
    Measurement of change from baseline to post-op in Ocular Surface Disease Index (OSDI) and Symptom Assessment iN Dry Eye (SANDE) scores



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female participants age 18 to <80 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02592330


Contacts
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Contact: Lynette Johns, OD 617-596-3655 lynette_johns@meei.harvard.edu
Contact: Stacey Ellender, PhD 617-573-6060 stacey_ellender@meei.harvard.edu

Locations
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United States, Massachusetts
Massachusetts Eye and Ear Infirmary Recruiting
Boston, Massachusetts, United States, 02114
Contact: Stacey Ellender, PhD    617-573-6060    stacey_ellender@meei.harvard.edu   
Contact: Lynette Johns, OD       lynette_johns@meei.harvard.edu   
Principal Investigator: Ula Jurkunas, MD         
Sub-Investigator: Jia Yin, MD, PhD         
Sponsors and Collaborators
Massachusetts Eye and Ear Infirmary
Dana-Farber Cancer Institute
Investigators
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Principal Investigator: Ula Jurkunas, MD Massachusetts Eye and Ear Infirmary

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Responsible Party: Ula Jurkunas, MD, Associate Professor, Harvard Medical School, Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier: NCT02592330    
Other Study ID Numbers: 14-124H
First Posted: October 30, 2015    Key Record Dates
Last Update Posted: January 29, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Ula Jurkunas, MD, Massachusetts Eye and Ear Infirmary:
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
Occular burn
Occular injury
Autograft
CLAU
Conjunctival Limbal Autograft
LSCD research
Chronic contact lens wear
Chronic keratoconjunctivitis
Corneal conjunctivalization
Corneal fibrovascular pannus
Corneal neovascularization
Corneal regeneration
Infectious keratitus
Limbal epithelial stem cell deficiency LESC
Ocular injury drug toxicity
Ocular surface disorder
Neovascularization pannus
Neurotrophic keratitis