Efficacy of Locally Delivered Allogeneic Mesenchymal Stromal Cells

NCT ID: NCT05705024

Last Updated: 2025-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

38 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-29

Study Completion Date

2026-09-28

Brief Summary

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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.

Detailed Description

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The "Efficacy of Locally Delivered Allogeneic Mesenchymal Stem Cells for Promoting Corneal Repair Study" otherwise known as the "MSC Study," is designed to assess the safety of allogeneic bone marrow-derived MSC secreted factor on the ocular surface via subconjunctival injection of MSC, and also obtain a preliminary observation on the following:

* Epithelial barrier integrity and/or wound closure.
* Development of Scarring.
* Final Visual Acuity.

The objective is to improve clinical outcomes in significant non-healing corneal wounds. To achieve these goals, the MSC Study will include a Phase II efficacy study.

Conditions

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Corneal Ulcer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers
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.

Study Groups

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Medium dose of allogenic MSC drops

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

Group Type ACTIVE_COMPARATOR

Mesenchymal Stromal Cells

Intervention Type 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.

Control Group

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

Group Type SHAM_COMPARATOR

Control Solution

Intervention Type OTHER

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

Interventions

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Mesenchymal Stromal Cells

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.

Intervention Type BIOLOGICAL

Control Solution

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

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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.

Exclusion Criteria

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.
* Use of any investigational agent within 4 weeks of screening visit.
* Participation in another clinical study at the same time as the present study.
* Participants who are pregnant at the time of study enrollment will be excluded; pregnancy is identified according to the patient's self-report /positive βhCG
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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United States Department of Defense

FED

Sponsor Role collaborator

University of Illinois at Chicago

OTHER

Sponsor Role lead

Responsible Party

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Ali R Djalilian

Professor of Ophthalmology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ali R Djalilian, MD

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Charlotte E Joslin, OD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Locations

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Department of Ophthalmology and Visual Sciences

Chicago, Illinois, United States

Site Status RECRUITING

University of Maryland at Baltimore

Baltimore, Maryland, United States

Site Status RECRUITING

Mass Eye and Ear Infirmary

Boston, Massachusetts, United States

Site Status ACTIVE_NOT_RECRUITING

University of Pennsylvania, Scheie Eye Institute

Philadelphia, Pennsylvania, United States

Site Status ACTIVE_NOT_RECRUITING

Countries

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United States

Central Contacts

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Ali R Djalilian, MD

Role: CONTACT

312-996-8937

Charlotte E Joslin, OD, PhD

Role: CONTACT

312-996-5410

Facility Contacts

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Ali R Djalilian, MD

Role: primary

312-996-8937

Charlotte E Joslin, OD, PhD

Role: backup

312-996-5410

Sarah Sunshine, MD

Role: primary

Megan Utz

Role: backup

References

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Bara JJ, Richards RG, Alini M, Stoddart MJ. Concise review: Bone marrow-derived mesenchymal stem cells change phenotype following in vitro culture: implications for basic research and the clinic. Stem Cells. 2014 Jul;32(7):1713-23. doi: 10.1002/stem.1649.

Reference Type BACKGROUND
PMID: 24449458 (View on PubMed)

Cook N, Hansen AR, Siu LL, Abdul Razak AR. Early phase clinical trials to identify optimal dosing and safety. Mol Oncol. 2015 May;9(5):997-1007. doi: 10.1016/j.molonc.2014.07.025. Epub 2014 Aug 14.

Reference Type BACKGROUND
PMID: 25160636 (View on PubMed)

Al-Moujahed A, Chodosh J. Outcomes of an algorithmic approach to treating mild ocular alkali burns. JAMA Ophthalmol. 2015 Oct;133(10):1214-6. doi: 10.1001/jamaophthalmol.2015.2302. No abstract available.

Reference Type BACKGROUND
PMID: 26226389 (View on PubMed)

Ghazaryan E, Zhang Y, He Y, Liu X, Li Y, Xie J, Su G. Mesenchymal stem cells in corneal neovascularization: Comparison of different application routes. Mol Med Rep. 2016 Oct;14(4):3104-12. doi: 10.3892/mmr.2016.5621. Epub 2016 Aug 11.

Reference Type BACKGROUND
PMID: 27514011 (View on PubMed)

U.S. Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research. Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products,. Accessed September 26, 2017. https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM564952.pdf

Reference Type BACKGROUND

Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. 2014 Mar 19;8:571-9. doi: 10.2147/OPTH.S45921. eCollection 2014.

Reference Type BACKGROUND
PMID: 24672223 (View on PubMed)

Bonini S, Rama P, Olzi D, Lambiase A. Neurotrophic keratitis. Eye (Lond). 2003 Nov;17(8):989-95. doi: 10.1038/sj.eye.6700616.

Reference Type BACKGROUND
PMID: 14631406 (View on PubMed)

Semeraro F, Forbice E, Romano V, Angi M, Romano MR, Filippelli ME, Di Iorio R, Costagliola C. Neurotrophic keratitis. Ophthalmologica. 2014;231(4):191-7. doi: 10.1159/000354380. Epub 2013 Oct 2.

Reference Type BACKGROUND
PMID: 24107451 (View on PubMed)

Stevens S. Administering a subconjunctival injection. Community Eye Health. 2009 Mar;22(69):15. No abstract available.

Reference Type BACKGROUND
PMID: 19506718 (View on PubMed)

Baradaran-Rafii A, Eslani M, Haq Z, Shirzadeh E, Huvard MJ, Djalilian AR. Current and Upcoming Therapies for Ocular Surface Chemical Injuries. Ocul Surf. 2017 Jan;15(1):48-64. doi: 10.1016/j.jtos.2016.09.002. Epub 2016 Sep 17.

Reference Type BACKGROUND
PMID: 27650263 (View on PubMed)

Eslani M, Baradaran-Rafii A, Movahedan A, Djalilian AR. The ocular surface chemical burns. J Ophthalmol. 2014;2014:196827. doi: 10.1155/2014/196827. Epub 2014 Jul 1.

Reference Type BACKGROUND
PMID: 25105018 (View on PubMed)

Bartlett RS, Guille JT, Chen X, Christensen MB, Wang SF, Thibeault SL. Mesenchymal stromal cell injection promotes vocal fold scar repair without long-term engraftment. Cytotherapy. 2016 Oct;18(10):1284-96. doi: 10.1016/j.jcyt.2016.07.005.

Reference Type BACKGROUND
PMID: 27637759 (View on PubMed)

Cockerham GC, Lemke S, Rice TA, Wang G, Glynn-Milley C, Zumhagen L, Cockerham KP. Closed-globe injuries of the ocular surface associated with combat blast exposure. Ophthalmology. 2014 Nov;121(11):2165-72. doi: 10.1016/j.ophtha.2014.06.009. Epub 2014 Aug 11.

Reference Type BACKGROUND
PMID: 25124272 (View on PubMed)

Cockerham GC, Lemke S, Glynn-Milley C, Zumhagen L, Cockerham KP. Visual performance and the ocular surface in traumatic brain injury. Ocul Surf. 2013 Jan;11(1):25-34. doi: 10.1016/j.jtos.2012.09.004. Epub 2012 Oct 5.

Reference Type BACKGROUND
PMID: 23321357 (View on PubMed)

Cockerham GC, Rice TA, Hewes EH, Cockerham KP, Lemke S, Wang G, Lin RC, Glynn-Milley C, Zumhagen L. Closed-eye ocular injuries in the Iraq and Afghanistan wars. N Engl J Med. 2011 Jun 2;364(22):2172-3. doi: 10.1056/NEJMc1010683. No abstract available.

Reference Type BACKGROUND
PMID: 21631351 (View on PubMed)

Baradaran-Rafii A, Eslani M, Tseng SC. Sulfur mustard-induced ocular surface disorders. Ocul Surf. 2011 Jul;9(3):163-78. doi: 10.1016/s1542-0124(11)70026-x.

Reference Type BACKGROUND
PMID: 21791191 (View on PubMed)

Prockop DJ, Oh JY. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol Ther. 2012 Jan;20(1):14-20. doi: 10.1038/mt.2011.211. Epub 2011 Oct 18.

Reference Type BACKGROUND
PMID: 22008910 (View on PubMed)

Mittal SK, Omoto M, Amouzegar A, Sahu A, Rezazadeh A, Katikireddy KR, Shah DI, Sahu SK, Chauhan SK. Restoration of Corneal Transparency by Mesenchymal Stem Cells. Stem Cell Reports. 2016 Oct 11;7(4):583-590. doi: 10.1016/j.stemcr.2016.09.001. Epub 2016 Sep 29.

Reference Type BACKGROUND
PMID: 27693426 (View on PubMed)

Wang LT, Ting CH, Yen ML, Liu KJ, Sytwu HK, Wu KK, Yen BL. Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials. J Biomed Sci. 2016 Nov 4;23(1):76. doi: 10.1186/s12929-016-0289-5.

Reference Type BACKGROUND
PMID: 27809910 (View on PubMed)

Yun YI, Park SY, Lee HJ, Ko JH, Kim MK, Wee WR, Reger RL, Gregory CA, Choi H, Fulcher SF, Prockop DJ, Oh JY. Comparison of the anti-inflammatory effects of induced pluripotent stem cell-derived and bone marrow-derived mesenchymal stromal cells in a murine model of corneal injury. Cytotherapy. 2017 Jan;19(1):28-35. doi: 10.1016/j.jcyt.2016.10.007. Epub 2016 Nov 10.

Reference Type BACKGROUND
PMID: 27840134 (View on PubMed)

Ye J, Yao K, Kim JC. Mesenchymal stem cell transplantation in a rabbit corneal alkali burn model: engraftment and involvement in wound healing. Eye (Lond). 2006 Apr;20(4):482-90. doi: 10.1038/sj.eye.6701913.

Reference Type BACKGROUND
PMID: 15895027 (View on PubMed)

Yao L, Li ZR, Su WR, Li YP, Lin ML, Zhang WX, Liu Y, Wan Q, Liang D. Role of mesenchymal stem cells on cornea wound healing induced by acute alkali burn. PLoS One. 2012;7(2):e30842. doi: 10.1371/journal.pone.0030842. Epub 2012 Feb 17.

Reference Type BACKGROUND
PMID: 22363499 (View on PubMed)

Roddy GW, Oh JY, Lee RH, Bartosh TJ, Ylostalo J, Coble K, Rosa RH Jr, Prockop DJ. Action at a distance: systemically administered adult stem/progenitor cells (MSCs) reduce inflammatory damage to the cornea without engraftment and primarily by secretion of TNF-alpha stimulated gene/protein 6. Stem Cells. 2011 Oct;29(10):1572-9. doi: 10.1002/stem.708.

Reference Type BACKGROUND
PMID: 21837654 (View on PubMed)

Oh JY, Kim MK, Shin MS, Lee HJ, Ko JH, Wee WR, Lee JH. The anti-inflammatory and anti-angiogenic role of mesenchymal stem cells in corneal wound healing following chemical injury. Stem Cells. 2008 Apr;26(4):1047-55. doi: 10.1634/stemcells.2007-0737. Epub 2008 Jan 10.

Reference Type BACKGROUND
PMID: 18192235 (View on PubMed)

Ma Y, Xu Y, Xiao Z, Yang W, Zhang C, Song E, Du Y, Li L. Reconstruction of chemically burned rat corneal surface by bone marrow-derived human mesenchymal stem cells. Stem Cells. 2006 Feb;24(2):315-21. doi: 10.1634/stemcells.2005-0046. Epub 2005 Aug 18.

Reference Type BACKGROUND
PMID: 16109757 (View on PubMed)

Li F, Zhao SZ. Control of Cross Talk between Angiogenesis and Inflammation by Mesenchymal Stem Cells for the Treatment of Ocular Surface Diseases. Stem Cells Int. 2016;2016:7961816. doi: 10.1155/2016/7961816. Epub 2016 Mar 24.

Reference Type BACKGROUND
PMID: 27110252 (View on PubMed)

Cejkova J, Trosan P, Cejka C, Lencova A, Zajicova A, Javorkova E, Kubinova S, Sykova E, Holan V. Suppression of alkali-induced oxidative injury in the cornea by mesenchymal stem cells growing on nanofiber scaffolds and transferred onto the damaged corneal surface. Exp Eye Res. 2013 Nov;116:312-23. doi: 10.1016/j.exer.2013.10.002. Epub 2013 Oct 18.

Reference Type BACKGROUND
PMID: 24145108 (View on PubMed)

Putra I, Shen X, Anwar KN, Rabiee B, Samaeekia R, Almazyad E, Giri P, Jabbehdari S, Hayat MR, Elhusseiny AM, Ghassemi M, Mahmud N, Edward DP, Joslin CE, Rosenblatt MI, Dana R, Eslani M, Hematti P, Djalilian AR. Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair. Transl Vis Sci Technol. 2021 Aug 12;10(10):3. doi: 10.1167/tvst.10.10.3.

Reference Type BACKGROUND
PMID: 34383879 (View on PubMed)

Jabbehdari S, Yazdanpanah G, Kanu LN, Anwar KN, Shen X, Rabiee B, Putra I, Eslani M, Rosenblatt MI, Hematti P, Djalilian AR. Reproducible Derivation and Expansion of Corneal Mesenchymal Stromal Cells for Therapeutic Applications. Transl Vis Sci Technol. 2020 Feb 21;9(3):26. doi: 10.1167/tvst.9.3.26.

Reference Type BACKGROUND
PMID: 32742756 (View on PubMed)

Other Identifiers

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W81XWH-18-1-0661

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2022-0751

Identifier Type: -

Identifier Source: org_study_id