Efficacy of Locally Delivered Allogeneic Mesenchymal Stromal Cells

Официальное название

Efficacy of Locally Delivered Allogeneic Mesenchymal Stem Cells for Promoting Corneal Repair

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Improvement of Corneal Epithelial Barrier and/or Integrity (Efficacy Rate) [Срок оценки: Day 28]

Вторичные конечные точки (9)

• Visual Acuity [Срок оценки: Baseline, Days 1-7, 28, 60, 90]
• Corneal staining and NEI grading [Срок оценки: Baseline, Days 1-7, 28, 60, 90]
• Ocular Surface Parameters [Срок оценки: Baseline, Day 28, 90]
• Corneal Epithelial Thickness [Срок оценки: Day 28, 90]
• Patient Symptoms [Срок оценки: Baseline, Days 1-7, 28, 60, 90]
• Time to epithelial healing [Срок оценки: Baseline, Days 1-7, 28, 60, 90]
• Corneal Scar [Срок оценки: Baseline, Days 1-7, 28, 60, 90]
• Corneal Neo-vascularization [Срок оценки: Baseline, Days 1-7, 28, 60, 90]
• Conjunctival injection [Срок оценки: Baseline, Days 1-7, 28, 60, 90]

Критерии участия

Критерии включения

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.

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 4 центра

• Department of Ophthalmology and Visual Sciences — Chicago
• University of Maryland at Baltimore — Baltimore
• Mass Eye and Ear Infirmary — Boston
• University of Pennsylvania, Scheie Eye Institute — Philadelphia

Публикации

• 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. PMID 25124272
• 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. PMID 23321357
• 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. PMID 21631351
• 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. PMID 21791191
• 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. PMID 22008910
• 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. PMID 27693426
• 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. PMID 27809910
• 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. PMID 27840134

Идентификаторы

NCT: NCT05705024 · 2022-0751 · W81XWH-18-1-0661

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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