Stem Cell Therapy for Limbal Stem Cell Deficiency

Safety and Feasibility of Cultivated Autologous Limbal Stem Cells (cLSC) for Limbal Stem Cell Deficiency

This phase I study will collect preliminary information on the activity and safety of cLSC. We will investigate the ability to manufacture and transplant cLSC onto the cornea successfully at the time of surgery (feasibility), and have cLSC begin to populate the ocular surface (efficacy) without serious adverse events (safety).

Study Overview

• Status: Recruiting
• Conditions: Limbal Stem-cell Deficiency
• Intervention / Treatment: Biological: cLSC; Device: Scleral contact lens (SCL)

Detailed Description

20 patients with severe to total Limbal Stem Cell Deficiency (LSCD) in one eye attributable to injury or ocular surgery. The first 5 eyes will receive the cLSCs to determine the feasibility and safety. Then the subsequent 15 eyes will be randomized into cLSC group and a scleral lens treatment (SCL) control group in a 2:1 ratio in blocks of 3 or 6 using a random number generator.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clemence Bonnet, MD, PhD; Phone Number: 310-825-6232; Email: CBonnet@mednet.ucla.edu
• Study Contact Backup: Name: Maricarmen Contreras, BA; Phone Number: 310-794-5593; Email: MariContreras@mednet.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California
      • Contact: Clemence Bonnet, MD; Phone Number: 310-794-7813

Participation Criteria

Eligibility Criteria

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

Description

Main inclusion Criteria:

1. Male or female ≥18 years of age.
2. Best corrected visual acuity in the affected eye of 20/200 or less.
3. Documentation of a LSCD diagnosis and the central cornea is affected.
4. Absence of lagophthalmos and eyelid abnormality
5. Adequate forniceal depth is ≥ 5 mm.
6. LSCD fails to resolve by surgical treatments of the ocular surface during the previous 6 months of screening visit.
7. If the etiology of LSCD is due to chemical injury, a minimal interval of 1 year since the initial chemical injury is required.
8. A Schirmer test result at 5 minute of ≥5 mm of wetting.
9. Absence of active infectious keratitis in either eye at the Enrollment Visit.
10. Have a life expectancy ≥ 2 years after enrollment.

Main exclusion Criteria:

1. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
2. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
3. Exposure keratopathy or lagophthalmos of the study eye.
4. Persistent severe ocular surface inflammation and/or meibomian gland dysfunction
5. Chemical injury occurred less than 12 months ago.
6. Presence of ocular surface tumor.
7. Uncontrolled diabetes with last hemoglobin A1C (HgA1C) >8.5.
8. Presence of known allergies to any of the cLSC components.
9. Current participation in another simultaneous medical investigation or trial.
10. Unable to be compliant with or complete the requirements of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cultivated Limbal Stem-Cells (cLSC); One dose of cultivated limbal stem-cells (cLSC), size between 7.6 to 15 mm in the average diameter.	Biological: cLSC; Transplantation of cLSC
Active Comparator: Scleral Contact Lens Device (SCL); Scleral contact lens device (SCL) will be fitted to stabilize and improve ocular surface.	Device: Scleral contact lens (SCL); Scleral contact lens device (SCL) will be used to stabilize and improve ocular surface.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of cLSC Transplant pertaining to Infection and/or Corneal Perforation	Safety assessed by incidence of Serious Adverse Events (SAEs) directly related to cLSC: infection and/or corneal perforation.	12 months for all participants
Feasibility of cLSC Transplant pertaining to Manufacturing meeting Release Criteria	Feasibility assessed by successful manufacturing of cLSC from biopsy that meets release criteria.	12 months for all participants
Feasibility of cLSC Transplant pertaining to Manufacturing without Contamination	Feasibility assessed by successful cLSC manufacturing without contamination.	12 months for all participants

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the Area of Corneal Epithelial Defect	Evaluate changes in the area of corneal epithelial defect (ED) or lack of ED.	At 6 months and 12 months in both cLSC and the control groups
Changes in the Clinical Score	Evaluate changes in the clinical score determined by slit lamp examination using fluorescein staining and confocal imaging.	At 6 months and 12 months in both cLSC and the control groups

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: National Eye Institute (NEI); California Institute for Regenerative Medicine (CIRM)
• Investigators: Principal Investigator: Sophie Deng, MD, PhD, Stein Eye Institute UCLA

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): May 31, 2024

Study Registration Dates

• First Submitted: February 21, 2019
• First Submitted That Met QC Criteria: May 17, 2019
• First Posted (Actual): May 21, 2019

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Limbal Stem Cell Deficiency
• Other Study ID Numbers: V001; R01EY021797 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes