Mesenchymal Stromal CellsEarly Phase 1MSC SecretomeNCT05204329
Safety of Topical Mesenchymal Stromal Cell Secretome for Ocular Surface Disease
A Early Phase 1 study testing MSC Secretome Eye Drops in people with Mesenchymal Stromal Cells and Cornea, run by University of Illinois at Chicago at 1 site 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 topical MSC Secretome eye drops. The study will be conducted at Illinois Eye and Ear Infirmary located at University of Illinois at Chicago. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mesenchymal Stromal Cells, Cornea, Corneal Defect
- What is being tested?
- MSC Secretome Eye Drops
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jan 2024to 8 Nov 2024
- Phase
- Early Phase 1
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
- Patients 18 years of age or older
- Chronic corneal epithelial disease with fluorescein staining score ≥ 6 by NEI grading scale
- Reduced corneal sensation (≤ 4 cm measured by Cochet Bonnet esthesiometry) in at least one corneal quadrant
- A stable ocular surface with no objective clinical evidence of significant (> 50%) improvement/worsening of the epithelial disease in the last 30 days
- Epithelial disease refractory to conventional non-surgical treatments (e.g., preservative-free artificial tears, gels or ointments; discontinuation of preserved topical drops; anti-inflammatory therapy)
Who cannot join
- Any active or suspected ocular infection (bacterial, viral, fungal or protozoal).
- Evidence of corneal ulceration with stromal loss > 10%
- Presence of an epithelial defect ≥1.0 mm in the largest diameter in the affected eye
- Presence of any size epithelial defect that has been persistent for more than 30 days
- Patients unable to discontinue or intermittently remove therapeutic contact lens in the study eye (to apply drops) during the 4-week study period
- History of any ocular surgery (including laser or refractive surgical procedures) in the affected eye within the 3 months prior to study enrollment
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- History of chemical injury within the last 6 months prior to study enrollment 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
- History of previous enrollment in the MSC Secretome Study at a lower dose
- 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
1 site in 1 country.
United States1 site
University of Illinois at Chicago
Chicago, Illinois, 60612
About this study
This study is a longitudinal assessment using a classic dose-escalation study design to assess the safety and maximal tolerated dose (MTD) of topical MSC Secretome eye drops. The study will be conducted at Illinois Eye and Ear Infirmary located at University of Illinois at Chicago. The study will use anterior segment Optical Coherence Tomography (OCT)/Scheimpflug Imaging, esthesiometry, and visual analogue scale (VAS) to assess treatment tolerability.
Read the detailed description
The "Safety of Topical Mesenchymal Stromal Cell Secretome for Ocular Surface Disease" study is designed to evaluate the safety and maximal tolerated dose (MTD) of topical MSC Secretome eye drops in patients with chronic ocular surface disease through a dose-escalation study under a 28-day topical application protocol, and also obtain a preliminary observation on the following:
- Incidence of treatment emergent adverse events (TEAE) assessed at 28 days following treatment initiation
- Proportion of patients with improved corneal epithelial barrier at 28 days compared to baseline
- Final visual acuity, corneal epithelial thickness, corneal stromal haze, corneal sensation, and treatment tolerability
The objective is to determine the dose of MSC Secretome through a first-in-human study through a dose-escalation strategy targeting a toxicity rate of 33% or less.
- Being tested
- MSC Secretome Eye Drops
- Keywords
- Mesenchymal Stromal Cells, Corneal Defect, Corneal Epithelium 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.
MSC Secretome Eye DropsBiological
MSC Secretome eye drop will be dispensed.
| Study group | Role | What they receive |
|---|---|---|
| Low dose of allogenic MSC drops | Active comparator | Escalating doses of allogenic MSC eye drops will be assigned at the lowest dose level. Receives: Biological: MSC Secretome Eye Drops |
| Medium dose of allogenic MSC drops | Active comparator | Escalating doses of allogenic MSC eye drops will be assigned at the medium dose level. Receives: Biological: MSC Secretome Eye Drops |
| High dose of allogenic MSC drops | Active comparator | Escalating doses of allogenic MSC eye drops will be assigned at the high dose level. Receives: Biological: MSC Secretome Eye Drops |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Participants In Each Dose Frequency Group With No Dose Limiting Toxicities Until Day 28 From The Start of Topical Allogeneic BM-MSC Secretome
Safety was defined with the absence of dose-limiting toxicity in the study eye until Day 28. Adverse events were defined using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v5). Ocular adverse events included:
Grade 2: vision loss ≤ 3 lines
- increased corneal fluorescein staining by >50%
- new conjunctivitis, scleritis, or uveitis 1-2+ cells in AC
- increased corneal haze > 50%, stromal loss 10-30% Grade 3: loss of vision by > 3 lines up to 20/200
- new mild to moderate infectious/inflammatory keratitis with vision loss up to 20/200
- new corneal ulceration with > 30% stromal loss
- new uveitis with 3-4+ cells in AC Grade 4: loss of vision by > 3 lines worse than 20/200
- new severe infectious/inflammatory keratitis
- corneal perforation
- Anaphylactic reaction, New SJS Note: Any grade 2 adverse event that lasted longer than 2 weeks or any adverse event of grades 3 or 4 was considered DLT. We also recorded all adverse events at each visit.
Measured: Day 28
Corneal Epithelial Integrity
The primary efficacy outcome measure was improved corneal epithelial barrier at 28 days compared to baseline - defined as ≥ 50% reduction in corneal fluorescein staining score using National Eye Institute (NEI) grading scale as measured by the investigators via slit lamp examination and assessment of slit lamp images.
Measured: Day 28
Secondary outcomes (6)
Visual Acuity
Mean Change in best-corrected distance visual acuity (BCVA) in ETDRS letters on day 28 relative to baseline for each dose frequency group. The ETDRS letter score ranges from 0 to 100, where higher scores indicate better visual acuity.
Measured: Day 28
Change in Corneal Scarring / Haze Compared to Baseline
Corneal scarring/haze was assessed as the size of the hyperreflective area on AS OCT imaging (Cirrus 6000; HD cornea, a-scans) to assess the treatment effect on DAY #28 relative to baseline.
Measured: Day 28
Time to Improvement of Corneal Epithelial Barrier
The time required for an improved epithelial barrier function was assessed at each visit throughout the trial.
Measured: Baseline, Days 7, 14, 28, 56, 90
Tolerability of MSC Secretome Drops (Change in VAS Score on Day 28 Compared to Baseline)
Mean change in the patients' self-reported severity of discomfort and pain with visual analog scale (VAS; range 0 -100) on Day 28 compared to baseline for each dose frequency group. The higher numbers indicate more severe discomfort and pain.
Measured: Day 28
Change in Central Corneal Epithelial Thickness
Mean change in Central Corneal Epithelial Thickness on Day 28 from baseline.
Measured: Day 28
Durability of Corneal Epithelial Status Improvement
In patients with an improvement in corneal epithelial integrity defined as ≥50% improvement in corneal fluorescein staining with NEI scale on Day 28 from baseline, was the improvement maintained on Days 42, 56 and 90.
Measured: Days 42, 56, 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2022
- Study start24 Jan 2024
- Primary completion8 Nov 2024
- Study completion8 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Mesenchymal Stromal CellsStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- A longitudinal assessment using a classic dose-escalation study design to evaluate the safety and maximal tolerated dose of topical MSC Secretome eye drops
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Illinois at Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- National Eye Institute (NEI), National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Ali R Djalilian, University of Illinois at Chicago
- Investigators
- Ali R Djalilian, MD, Principal investigator, University of Illinois at ChicagoCharlotte E Joslin, OD, PhD, Principal investigator, University of Illinois at ChicagoElmer Y Tu, MD, Principal investigator, University of Illinois at Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05204329
- Sponsor's protocol ID
- 2021-0754
- Other IDs
- 1UG3EY031809-01
- Acronym
- MSC Secretome
- Status last verified
- Oct 2026
- First submitted
- 11 Jan 2022
- Last updated
- 7 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
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 27840134Yao 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 18192235Ma 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.
PubMed 16109757Li 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.
PubMed 27110252Cejkova 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.
PubMed 24145108Eslani M, Putra I, Shen X, Hamouie J, Afsharkhamseh N, Besharat S, Rosenblatt MI, Dana R, Hematti P, Djalilian AR. Corneal Mesenchymal Stromal Cells Are Directly Antiangiogenic via PEDF and sFLT-1. Invest Ophthalmol Vis Sci. 2017 Oct 1;58(12):5507-5517. doi: 10.1167/iovs.17-22680.
PubMed 29075761Uccelli A, de Rosbo NK. The immunomodulatory function of mesenchymal stem cells: mode of action and pathways. Ann N Y Acad Sci. 2015 Sep;1351:114-26. doi: 10.1111/nyas.12815. Epub 2015 Jul 6.
PubMed 26152292Coulson-Thomas VJ, Coulson-Thomas YM, Gesteira TF, Kao WW. Extrinsic and Intrinsic Mechanisms by Which Mesenchymal Stem Cells Suppress the Immune System. Ocul Surf. 2016 Apr;14(2):121-34. doi: 10.1016/j.jtos.2015.11.004. Epub 2016 Jan 12.
PubMed 26804815Maguire G. Stem cell therapy without the cells. Commun Integr Biol. 2013 Nov 1;6(6):e26631. doi: 10.4161/cib.26631. Epub 2013 Sep 27.
PubMed 24567776Madrigal M, Rao KS, Riordan NH. A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods. J Transl Med. 2014 Oct 11;12:260. doi: 10.1186/s12967-014-0260-8.
PubMed 25304688