Efficacy of Locally Delivered Allogeneic Mesenchymal Stromal Cells

NCT05705024 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2022-0751W81XWH-18-1-0661
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 4

Brief Summary

The proposed Conventional Cohort Expansion Study involves the use of Mesenchymal Stromal Cells (MSCs) are derived from the bone marrow. We previously studied the safety of subconjunctival injection of allogeneic bone marrow-derived MSCs in patients with nonhealing epitheliopathy (IRB Protocol 2020-0334). In the present study, we want to study the efficacy of this treatment on chronic epitheliopathies.

Conditions

Corneal Ulcer

Outcome Measures

Primary Outcomes (1)

• Improvement of Corneal Epithelial Barrier and/or Integrity (Efficacy Rate)

  The proportion of patients with improved epithelial barrier and/or integrity from baseline to DAY 28 as determined by the investigator on slit lamp examination: * Improved epithelial barrier, defined as a 50 % improvement in corneal fluorescein staining score * Improved epithelial integrity, defined as a healed epithelial defect

  Day 28

Secondary Outcomes (9)

• Visual Acuity

  Baseline, Days 1-7, 28, 60, 90

• Corneal staining and NEI grading

  Baseline, Days 1-7, 28, 60, 90

• Ocular Surface Parameters

  Baseline, Day 28, 90

• Corneal Epithelial Thickness

  Day 28, 90

• Patient Symptoms

  Baseline, Days 1-7, 28, 60, 90

Study Arms (2)

Medium dose of allogenic MSC drops

ACTIVE COMPARATOR

Dose of allogeneic MSC subconjunctival injection will be assigned 3,000,000 cells/150 µL.

Biological: Mesenchymal Stromal Cells

Control Group

SHAM COMPARATOR

For the control group, 50 µL of the freezing media (vehicle) will be injected.

Other: Control Solution

Interventions

Control Solution OTHER

For the control group, 150 µL of injectable normal saline (0.9% NaCl). will be injected.

Control Group

Mesenchymal Stromal Cells BIOLOGICAL

Subconjunctival Injection of Allogeneic Mesenchymal Stromal Cellsmasked clinical trial, patients with non-resolving corneal epithelial disease (i.e., refractory to standard treatments for at least two weeks) will receive a single subconjunctival injection of bone marrow-derived allogeneic MSCs or vehicle (CS5 freezing media, BioLife Solutions Inc, Bothell, WA, USA), with continued follow-up for up to 90 days.

Medium dose of allogenic MSC drops

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Visual Acuity:
• Best corrected distance visual acuity (BCDVA) score ≤ 75 ETDRS letters, (≥ 0.2 LogMAR, ≤ 20/32 Snellen or ≤ 0.625 decimal fraction) in the affected eye.
• Ocular Health:
• Patients with non-resolving corneal epitheliopathy or epithelial defect after two or more weeks of standard non-surgical treatments (e.g., preservative-free artificial tears, gels or ointments; discontinuation of preserved topical drops; anti-inflammatory therapy, soft bandage contact lens).
• No objective clinical evidence of improvement in the last 2 weeks (≤50% reduction in fluorescein staining or ≤50% reduction in longest diameter of the epithelial defect).
• If both eyes have chronic epithelial disease, the eye with the worse epithelial disease will be treated.
• Evidence of impaired epithelial barrier manifested by fluorescein staining of the epithelium with a score 10 or higher by National Eye Institute grading.
• Patients with stage 1 (no epithelial defect), stage 2 (persistent epithelial defect, PED; without stromal loss) or stage 3 (corneal ulcer; with stromal loss) neurotrophic keratopathy25-27 limited to ≤80% corneal diameter.
• Study Procedures:
• Only patients who satisfy all Informed Consent requirements may be included in the study. The patient and/or his/her legal representative must read, sign and date the Informed Consent document before any study-related procedures are performed. The Informed Consent form signed by patients and/or legal representatives must have been approved by the IRB for the current study.
• Patients must have the ability and willingness to comply with study procedures.

You may not qualify if:

• Visual Acuity:
• Best-corrected distance visual acuity (BCDVA) score better than 75 ETDRS letters, or 0.2 LogMAR, or 20/32 Snellen or 0.625 decimal fraction in the affected eye
• Ocular Health:
• Ocular drug toxicity less than two weeks ago
• Any active ocular infection (bacterial, viral, fungal or protozoal) or active ocular inflammation in the affected eye.
• History of any ocular surgery (including laser or refractive surgical procedures) in the affected eye within the three months before study enrollment. (An exception to the preceding statement will be allowed if the ocular surgery is considered to be the cause of the PED. Ocular surgery in the affected eye will not be allowed during the study treatment period and elective ocular surgery procedures should not be planned during the duration of the follow-up period unless the patient will be involved in corneal thinning of more than 1/3 corneal stroma, corneal melting or perforation.
• Prior surgical procedure(s) for the treatment of a chronic corneal epitheliopathy (e.g., complete tarsorrhaphy, conjunctival flap, etc.) in the affected eye with the exception of amniotic membrane transplantation. Patients previously treated with amniotic membrane transplantation may only be enrolled two weeks after the membrane has disappeared within the area of the chronic corneal epitheliopathy or corneal ulcer or at least six weeks after the date of the amniotic membrane transplantation procedure. Patients previously treated with Botox (botulinum toxin) injections used to induce pharmacologic blepharoptosis are eligible for enrollment only if the last injection was given at least 90 days prior to enrollment in the study.
• Chronic corneal epitheliopathy in the background of endothelial decompensation that needs corneal graft
• Anticipated need for punctual occlusion during the study treatment period. Patients with punctual occlusion or punctual plugs inserted prior to the study are eligible for enrollment provided that the punctual occlusion is maintained during the study.
• Evidence of corneal ulceration involving the posterior third of the corneal stroma, corneal melting or perforation in the affected eye.
• Presence or history of any ocular or systemic disorder or condition that might hinder the efficacy of the study treatment or its evaluation, could possibly interfere with the interpretation of study results, or could be judged by the investigator to be incompatible with the study visit schedule or conduct (e.g., progressive or degenerative corneal or retinal conditions, uveitis, optic neuritis, poorly controlled diabetes, autoimmune disease, systemic infection, neoplastic diseases).
• Patients with uncontrolled eyelid abnormality that preclude appropriate eyelid closure or including eyelash abnormality
• Study Procedures:
• Known hypersensitivity to one of the components of the study or procedural medications (e.g., fluorescein).
• History of drug, medication or alcohol abuse or addiction.

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• United States Department of Defense: collaborator

Study Sites (4)

Department of Ophthalmology and Visual Sciences

Chicago, Illinois, 60612, United States

RECRUITING

University of Maryland at Baltimore

Baltimore, Maryland, 21201, United States

RECRUITING

Mass Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

ACTIVE NOT RECRUITING

University of Pennsylvania, Scheie Eye Institute

Philadelphia, Pennsylvania, 19104, United States

ACTIVE NOT RECRUITING

Related Publications (29)

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MeSH Terms

Conditions

Corneal Ulcer

Condition Hierarchy (Ancestors)

Eye Infections; Infections; Keratitis; Corneal Diseases; Eye Diseases

Study Officials

• Ali R Djalilian, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

• Charlotte E Joslin, OD, PhD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ali R Djalilian, MD

CONTACT

312-996-8937; adjalili@uic.edu

Charlotte E Joslin, OD, PhD

CONTACT

312-996-5410; charjosl@uic.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Thirty eight (38) patients will be recruited in this randomized clinical trial study with a 2:1 allocation for randomization. Twenty-five (25) patients will be recruited for the MSC treatment and thirteen (13) patients will be assigned to the control group. At any stage, if the results of MSC group were significantly better than the control group, using the control group would be stopped. This process will be supervised by Charlotte Joselin who is the person in charge for blinding and for the formulation and distribution of the proper study drug for injection.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Ophthalmology

Study Record Dates

• First Submitted: January 21, 2023
• First Posted: January 30, 2023
• Study Start: September 29, 2023
• Primary Completion (Estimated): September 28, 2026
• Study Completion (Estimated): September 28, 2026
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)