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Safety and Feasibility of CALEC for LSCD (CALEC)

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ClinicalTrials.gov Identifier: NCT02592330
Recruitment Status : Recruiting
First Posted : October 30, 2015
Last Update Posted : March 6, 2018
Sponsor:
Collaborator:
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
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 Biological: CALEC Procedure: CLAU Phase 1

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. 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.


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
Actual Study Start Date : August 2016
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020

Arm Intervention/treatment
Experimental: CALEC
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.
Biological: CALEC
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

Active Comparator: 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
Donor tissue is obtained from the fellow eye (limbal autograft) with the goal of transplantation of a new source of epithelium for a diseased ocular surface after the removal of the recipient's scarred and diseased epithelium.
Other Name: Conjunctival Limbal Autograft




Primary Outcome Measures :
  1. Safety - The following adverse event will serve as a primary safety measure: ocular infection. [ Time Frame: 2 years ]

    To establish that CALEC transplantation has an acceptable safety profile by determining the incidence and severity of ocular adverse events, as identified by eye examination.

    Any adverse events, ocular or systemic, from all subjects will be utilized to summarize safety data for this pilot study. The severity of each adverse event and the relationship of the event to the cell therapy procedure will be assessed. The following adverse event will serve as a primary safety measure: ocular infection.


  2. Safety - The following adverse event will serve as a primary safety measure: corneal perforation. [ Time Frame: 2 years ]

    To establish that CALEC transplantation has an acceptable safety profile by determining the incidence and severity of ocular adverse events, as identified by eye examination.

    Any adverse events, ocular or systemic, from all subjects will be utilized to summarize safety data for this pilot study. The severity of each adverse event and the relationship of the event to the cell therapy procedure will be assessed. The following adverse event will serve as a primary safety measure: corneal perforation.


  3. Safety - The following adverse event will serve as a primary safety measure: graft detachment ≥ 50%. [ Time Frame: 2 years ]

    To establish that CALEC transplantation has an acceptable safety profile by determining the incidence and severity of ocular adverse events, as identified by eye examination.

    Any adverse events, ocular or systemic, from all subjects will be utilized to summarize safety data for this pilot study. The severity of each adverse event and the relationship of the event to the cell therapy procedure will be assessed. The following adverse event will serve as a primary safety measure: graft detachment ≥ 50%.


  4. Feasibility [ Time Frame: 2 years ]

    To establish feasibility of manufacturing CALEC for corneal transplantation.

    Any issues of processing corneal biopsies and development of CALEC constructs will be assessed. The following measure will serve as a primary feasibility measure: cell growth.


  5. Feasibility [ Time Frame: 2 years ]

    To establish feasibility of manufacturing CALEC for corneal transplantation.

    Any issues of processing corneal biopsies and development of CALEC constructs will be assessed. The following measure will serve as a primary feasibility measure: cell viability.


  6. Feasibility [ Time Frame: 2 years ]

    To establish feasibility of manufacturing CALEC for corneal transplantation.

    Any issues of processing corneal biopsies and development of CALEC constructs will be assessed. The following measure will serve as a primary feasibility measure: culture contamination.



Secondary Outcome Measures :
  1. Efficacy [ Time Frame: 2 years ]

    We will assess the efficacy of CALEC transplantation and standard autologous limbal graft on LSCD by comparing pre- and post-operative: corneal surface integrity. This will be defined as:

    • Decrease in frank epithelial defect surface area by >75%, or
    • Decrease in surface staining (NEI grading scale) by >50%

  2. Efficacy [ Time Frame: 2 years ]

    We will assess the efficacy of CALEC transplantation and standard autologous limbal graft on LSCD by comparing pre- and post-operative: extent of vascularization. This will be defined as:

    • Decrease in neovascular area by >25%

  3. Efficacy [ Time Frame: 2 years ]

    We will assess the efficacy of CALEC transplantation and standard autologous limbal graft on LSCD by comparing pre- and post-operative: patient symptomatology. This information will be determined by assessing:

    • Improvement (decrease) in Ocular Surface Disease Index (OSDI) or Symptom Assessment iN Dry Eye (SANDE)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or Female patients between the ages of 18 and 80 years old
  • 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
Contact: Lisa Langone 617-573-4437 lisa_langone@meei.harvard.edu

Locations
United States, Massachusetts
Massachusetts Eye and Ear Infirmary Recruiting
Boston, Massachusetts, United States, 02114
Contact: Lisa Langone       lisa_langone@meei.harvard.edu   
Principal Investigator: Ula Jurkunas, MD         
Principal Investigator: Ahmad Kheirkhah, MD         
Sponsors and Collaborators
Massachusetts Eye and Ear Infirmary
Dana-Farber Cancer Institute
Investigators
Principal Investigator: Ula Jurkunas, MD Massachusetts Eye and Ear Infirmary

Responsible Party: Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier: NCT02592330     History of Changes
Other Study ID Numbers: 14-124H
First Posted: October 30, 2015    Key Record Dates
Last Update Posted: March 6, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Massachusetts Eye and Ear Infirmary:
CALEC
Limbal Stem Cell Deficiency
LSCD