Mesenchymal Stromal CellsPhase 1NCT04626583
Safety of Locally Delivered Allogeneic Mesenchymal Stromal Cells
A Phase 1 study testing Allogeneic MSC in people with Mesenchymal Stromal Cells and Cornea, run by University of Illinois Chicago at 4 sites in United States.
Trial summary
This study is a longitudinal assessment using a classic dose-escalation study design to assess the safety and maximal tolerated dose (MTD) of locally delivered allogeneic mesenchymal stromal cells (MSC) for promoting corneal repair. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mesenchymal Stromal Cells, Cornea, Safety
- What is being tested?
- Allogeneic MSC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 4 sitesUnited States
- Study dates
- 5 Mar 2021to 21 Apr 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age:
- Patients 18 years of age or older
- 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 moderate to severe chronic corneal epithelial disease in the setting of neurotrophic keratitis, limbal stem cell deficiency, or inflammatory dry eye disease.
Show all 14Show fewer
- Epithelial disease refractory to all applicable standard / FDA approved non-surgical treatments (e.g., preservative-free artificial tears, gels or ointments; discontinuation of preserved topical drops; anti-inflammatory therapy, and soft bandage contact lens).
- Evidence of impaired epithelial barrier manifested by fluorescein staining of the epithelium with a score 6 or higher by National Eye Institute grading.
- No objective clinical evidence of improvement since the last visit (≤50% reduction in fluorescein staining or ≤50% reduction in longest diameter of the epithelial defect).
- 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 keratopathy 28-30 limited to ≤80% corneal diameter. Stromal loss in corneal ulcers cannot exceed 50%.
- Etiology of all persistent epithelial defects and corneal ulcers will be neurotrophic in nature. Neurotrophic keratopathy may be due to previous trauma such as chemical and thermal burns, systemic diseases like diabetes, post-infectious keratitis such as herpetic disease, or cranial nerve V palsies such as surgery for trigeminal neuralgia.
- PED or corneal ulceration refractory to one or more conventional non-surgical treatments (e.g., preservative-free artificial tears, gels or ointments; discontinuation of preserved topical drops and medications that can decrease corneal sensitivity; therapeutic contact lenses).
- No objective clinical evidence of improvement in the PED or corneal ulceration within the week prior to study enrollment (e.g., ≤50% reduction in longest diameter in 1 week).
- Evidence of decreased corneal sensitivity (≤ 4 cm using the Cochet-Bonnet aesthesiometer) within the area of the PED or corneal ulcer and outside of the area of the defect in at least one corneal quadrant.
Who cannot join
- Visual Acuity:
- Patients with severe vision loss in the affected eye with no potential for visual improvement in the opinion of the investigator as a result of the study treatment.
- Ocular Health:
- Any active ocular infection (bacterial, viral, fungal or protozoal) or active ocular inflammation not related to PED 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.
- Prior surgical procedure(s) for the treatment of a PED (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 PED 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.
Show all 16Show fewer
- 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).
- Any need for or anticipated change in the dose of systemic medications known to impair the function of the trigeminal nerve (e.g., neuroleptics, antipsychotic and antihistamine drugs). These treatments are allowed during the study if initiated prior to 30 days before study enrollment provided they remain stable throughout the course of the study treatment periods.
- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Maryland
Baltimore, Maryland, 21201
Mass Eye and Ear Institute
Boston, Massachusetts, 02114
University of Illinois, Department of Ophthalmology and Visual Sciences
Chicago, Illinois, 60612
University of Pennsylvania Scheie Eye Institute
Philadelphia, Pennsylvania, 19104
About this study
Official title: Safety of Locally Delivered Allogeneic Mesenchymal Stromal Cells for Promoting Corneal Repair
This study is a longitudinal assessment using a classic dose-escalation study design to assess the safety and maximal tolerated dose (MTD) of locally delivered allogeneic mesenchymal stromal cells (MSC) for promoting corneal repair. The study will be conducted at Illinois Eye and Ear Infirmary located at University of Illinois at Chicago. The study will use digital conjunctival and corneal photography and corneal Scheimpflug Imaging, densitometry, and pachymetry for assessment of safety and corneal wound healing.
Read the detailed description
The "Safety 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 I dose-escalation safety study.
- Conditions
- Mesenchymal Stromal Cells, Cornea, Safety, Corneal Defect
- Being tested
- Allogeneic MSC
- Keywords
- Mesenchymal Stromal Cells, Corneal Defect
- Medical subject headings
- Corneal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic MSCBiological
Subconjunctival Injection of Allogeneic Mesenchymal Stromal Cells
| Study group | Role | What they receive |
|---|---|---|
| Low dose of allogeneic MSC | Active comparator | Escalating doses of allogeneic MSC subconjunctival injection will be assigned 1,000,000 cells/50 µL at the low dose level. Receives: Biological: Allogeneic MSC |
| Medium dose of allogeneic MSC | Active comparator | Escalating doses of allogeneic MSC subconjunctival injection will be assigned 3,000,000 cells/150 µL at the medium dose level. Receives: Biological: Allogeneic MSC |
| High dose of allogeneic MSC | Active comparator | Escalating doses of allogeneic MSC subconjunctival injection will be assigned 6,000,000 cells total consisting of injection at 2 sites of 3,000,000 cells/150 µL each at the high dose level. Receives: Biological: Allogeneic MSC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Safety Outcome: Incidence of treatment emergent adverse events (TEAE) assessed at 28 days.
Slit lamp exam will assess the safety of the treatment via TEAE at 28 days (participants will receive continued monitoring through 90 days). TEAE will be defined according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5) adverse event reference, and used to identify dose-limiting toxicity (DLT).
The DLT will be defined as any non-corneal, ocular or systemic TEAE, with a Grade 2 toxicity without resolution after 14 days OR a Grade 3 toxicity, unless it can clearly be attributed to another cause. The DLT will be used to define the maximal tolerated dose (MTD).
The MTD will be defined as the highest dose at which 0 to 1 of 6 patients experiences a dose-limiting toxicity (DLT). If a DLT occurs in 2 patients in a dosing cohort, then the MTD is considered exceeded and the dose will not be escalated.
Measured: Day #28
Primary Efficacy Outcome: Proportion of participants with improvement in epithelial defect or barrier integrity relative to baseline (based on fluorescein staining)
Presence or absence of epithelial defect and epithelial staining grade following treatment, as determined by fluorescein staining observed via slit lamp examination, and photo-documented with digital corneal photography.
Measured: Day #28
Secondary outcomes (5)
Secondary Efficacy Outcomes: Visual Acuity
Best-corrected distance visual acuity will be measured using standard e-ETDRS protocols.
Measured: Enrollment, Treatment, and Days #1, #7, #14, #28, #90
Secondary Efficacy Outcomes: Time to Completion of Corneal Epithelialization
Time to completion of corneal epithelialization will be assessed at each visit throughout the trial. Corneal epithelialization will be assessed as previously described.
Measured: Enrollment, Treatment, and Days #1, #7, #14, #28, #90
Secondary Efficacy Outcomes: Durability of the Corneal Epithelialization and Healing
Durability of the corneal epithelization and healing will be assessed as an outcome measure at DAY #28 and DAY #90. Participants with corneal epithelialization prior to DAY #28 will be assessed at each subsequent follow-up visit (e.g., DAYS #7, #14, #28) to assess persistence of the healing response. Corneal epithelialization will be assessed as previously described.
Measured: Enrollment, Treatment, and Days #1, #7, #14, #28, #90
Secondary Efficacy Outcomes: Corneal stromal haze
Corneal stromal haze will be measured from Scheimpflug imaging and anterior segment OCT images (using Image J software). The treatment effect on corneal haze on DAY #28 will be compared relative to baseline.
Measured: Enrollment and Days #7, #14, #28, #90
Secondary Efficacy Outcomes: Corneal epithelial thickness
Corneal epithelial thickness measured by anterior segment OCT imaging will assess the treatment effect on thickness on DAY #28 and compared relative to baseline.
Measured: Enrollment and Days #7, #14, #28, #90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2020
- Study start5 Mar 2021
- Primary completion21 Apr 2023
- Study completion21 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (38)Papers the sponsor has linked to this study.
- Other trials for Mesenchymal Stromal CellsStudies of the same condition, open and under way.
- More trials run by University of Illinois ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- A longitudinal assessment using a classic dose-escalation study design to assess the safety of locally delivered allogenic mesenchymal stromal cells for promoting corneal repair.
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Illinois Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Principal investigator, Ali R Djalilian, University of Illinois Chicago
- Investigators
- Ali R Djalilian, MD, Principal investigator, University of Illinois ChicagoCharlotte E Joslin, OD, PhD, Principal investigator, University of Illinois Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04626583
- Sponsor's protocol ID
- 2020-0334
- Other IDs
- W81XWH-18-1-0661
- Status last verified
- Feb 2024
- First submitted
- 10 Nov 2020
- Last updated
- 16 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25124272Cockerham 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.
PubMed 23321357Cockerham 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.
PubMed 21631351Baradaran-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.
PubMed 21791191Baradaran-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.
PubMed 27650263Eslani 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.
PubMed 25105018Al-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.
PubMed 26226389Prockop 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.
PubMed 22008910Mittal 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.
PubMed 27693426Wang 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.
PubMed 27809910Yun 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.
PubMed 27840134Ye 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.
PubMed 15895027Yao 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.
PubMed 22363499Roddy 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.
PubMed 21837654Oh 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.
PubMed 18192235
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of Locally Delivered Allogeneic Mesenchymal Stromal Cells for Promoting Corneal Repair
- ClinicalTrials.gov ID
- NCT04626583
- Acronym / sponsor ID
- 2020-0334
- Conditions
- Mesenchymal Stromal Cells, Cornea, Safety, Corneal Defect
- Keywords
- Mesenchymal Stromal Cells, Corneal Defect
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of Illinois ChicagoUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 5 Mar 2021 (actual)
- Primary completion
- 21 Apr 2023 (actual)
- Study completion
- 21 Apr 2023 (actual)
- First posted
- 12 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a longitudinal assessment using a classic dose-escalation study design to assess the safety and maximal tolerated dose (MTD) of locally delivered allogeneic mesenchymal stromal cells (MSC) for promoting corneal repair. The study will be conducted at Illinois Eye and Ear Infirmary located at University of Illinois at Chicago. The study will use digital conjunctival and corneal photography and corneal Scheimpflug Imaging, densitometry, and pachymetry for assessment of safety and corneal wound healing.
Detailed description
The "Safety 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 I dose-escalation safety study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- A longitudinal assessment using a classic dose-escalation study design to assess the safety of locally delivered allogenic mesenchymal stromal cells for promoting corneal repair.
| Arm | Type | Receives |
|---|---|---|
| Low dose of allogeneic MSC | Active comparator | Biological: Allogeneic MSCEscalating doses of allogeneic MSC subconjunctival injection will be assigned 1,000,000 cells/50 µL at the low dose level. |
| Medium dose of allogeneic MSC | Active comparator | Biological: Allogeneic MSCEscalating doses of allogeneic MSC subconjunctival injection will be assigned 3,000,000 cells/150 µL at the medium dose level. |
| High dose of allogeneic MSC | Active comparator | Biological: Allogeneic MSCEscalating doses of allogeneic MSC subconjunctival injection will be assigned 6,000,000 cells total consisting of injection at 2 sites of 3,000,000 cells/150 µL each at the high dose level. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients 18 years of age or older
- 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.
- Patients with moderate to severe chronic corneal epithelial disease in the setting of neurotrophic keratitis, limbal stem cell deficiency, or inflammatory dry eye disease.
- Epithelial disease refractory to all applicable standard / FDA approved non-surgical treatments (e.g., preservative-free artificial tears, gels or ointments; discontinuation of preserved topical drops; anti-inflammatory therapy, and soft bandage contact lens).
- Evidence of impaired epithelial barrier manifested by fluorescein staining of the epithelium with a score 6 or higher by National Eye Institute grading.
Key exclusion criteria (16 listed)
- Patients with severe vision loss in the affected eye with no potential for visual improvement in the opinion of the investigator as a result of the study treatment.
- Any active ocular infection (bacterial, viral, fungal or protozoal) or active ocular inflammation not related to PED 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.
- Prior surgical procedure(s) for the treatment of a PED (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 PED 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allogeneic MSCSubconjunctival Injection of Allogeneic Mesenchymal Stromal Cells | Biological | High dose of allogeneic MSC, Low dose of allogeneic MSC, Medium dose of allogeneic MSC |
Primary outcome
Primary Safety Outcome: Incidence of treatment emergent adverse events (TEAE) assessed at 28 days.
Time frame: Day #28
Slit lamp exam will assess the safety of the treatment via TEAE at 28 days (participants will receive continued monitoring through 90 days). TEAE will be defined according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5) adverse event reference, and used to identify dose-limiting toxicity (DLT). The DLT will be defined as any non-corneal, ocular or systemic TEAE, with a Grade 2 toxicity without resolution after 14 days OR a Grade 3 toxicity, unless it can clearly be attributed to another cause. The DLT will be used to define the maximal tolerated dose (MTD). The MTD will be defined as the highest dose at which 0 to 1 of 6 patients experiences a dose-limiting toxicity (DLT). If a DLT occurs in 2 patients in a dosing cohort, then the MTD is considered exceeded and the dose will not be escalated.
Primary Efficacy Outcome: Proportion of participants with improvement in epithelial defect or barrier integrity relative to baseline (based on fluorescein staining)
Time frame: Day #28
Presence or absence of epithelial defect and epithelial staining grade following treatment, as determined by fluorescein staining observed via slit lamp examination, and photo-documented with digital corneal photography.
5 secondary outcomes
Secondary Efficacy Outcomes: Visual Acuity
Time frame: Enrollment, Treatment, and Days #1, #7, #14, #28, #90
Secondary Efficacy Outcomes: Time to Completion of Corneal Epithelialization
Time frame: Enrollment, Treatment, and Days #1, #7, #14, #28, #90
Secondary Efficacy Outcomes: Durability of the Corneal Epithelialization and Healing
Time frame: Enrollment, Treatment, and Days #1, #7, #14, #28, #90
Secondary Efficacy Outcomes: Corneal stromal haze
Time frame: Enrollment and Days #7, #14, #28, #90
Secondary Efficacy Outcomes: Corneal epithelial thickness
Time frame: Enrollment and Days #7, #14, #28, #90
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2024.
- Background: PubMed 25124272Cockerham 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.
- Background: PubMed 23321357Cockerham 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.
- Background: PubMed 21631351Cockerham 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.
- Background: PubMed 21791191Baradaran-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.
- Background: PubMed 27650263Baradaran-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.
- Background: PubMed 25105018Eslani 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.
- Background: PubMed 26226389Al-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.
- Background: PubMed 22008910Prockop 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.
- Background: PubMed 27693426Mittal 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.
- Background: PubMed 27809910Wang 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.
- Background: PubMed 27840134Yun 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.
- Background: PubMed 15895027Ye 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.
- Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy ProductsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Corneal Ulcer
Not yet recruitingPhase 1
ARTEMIS: UC-MSCs After Mechanical Thrombectomy for Acute Ischemic Stroke
Acute Ischemic Stroke
RecruitingPhase 2
Efficacy of Topical Mesenchymal Stromal Cell Secretome for Ocular Surface Disease
Persistent Corneal Epithelial Defect, Corneal Epithelial Disorders
RecruitingPhase 1/2
Stem Cell Therapy for Intracerebral Hemorrhage
Intracerebral Hemorrhage, Mesenchymal Stem Cell
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ali R Djalilian, MD principal investigator
University of Illinois Chicago
Charlotte E Joslin, OD, PhD principal investigator
University of Illinois Chicago
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Allogeneic MSC in people with Mesenchymal Stromal Cells and Cornea, run by University of Illinois Chicago at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Safety Outcome: Incidence of treatment emergent adverse events (TEAE) assessed at 28 days. (time frame: Day #28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04626583, which also lists 38 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2024.