drugset / Trial / NCT04626583
Safety of Locally Delivered Allogeneic Mesenchymal Stromal Cells
Phase 1
Completed
8 enrolled
University of Illinois at Chicago
United States Department of Defense · collab
Non-randomizedSequentialOpen-labelTreatment
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. 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.
Timeline
- Start
- 2021-03-05
- Primary completion
- 2023-04-21
- Completion
- 2023-04-21
Publications
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background Ivy SP, Siu LL, Garrett-Mayer E, Rubinstein L. Approaches to phase 1 clinical trial design focused on safety, efficiency, and selected patient populations: a report from the clinical trial design task force of the national cancer institute investigational drug steering committee. Clin Cancer Res. 2010 Mar 15;16(6):1726-36. doi: 10.1158/1078-0432.CCR-09-1961. Epub 2010 Mar 9.
- Background 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.
- Background Stevens S. Administering a subconjunctival injection. Community Eye Health. 2009 Mar;22(69):15. No abstract available.
- Background 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.
- 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.
- Background Bonini S, Rama P, Olzi D, Lambiase A. Neurotrophic keratitis. Eye (Lond). 2003 Nov;17(8):989-95. doi: 10.1038/sj.eye.6700616.
- Background 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.
- Background Arnalich-Montiel F, Hernandez-Verdejo JL, Oblanca N, Munoz-Negrete FJ, De Miguel MP. Comparison of corneal haze and visual outcome in primary DSAEK versus DSAEK following failed DMEK. Graefes Arch Clin Exp Ophthalmol. 2013 Nov;251(11):2575-84. doi: 10.1007/s00417-013-2460-y. Epub 2013 Sep 6.
- Background Elflein HM, Hofherr T, Berisha-Ramadani F, Weyer V, Lampe C, Beck M, Pitz S. Measuring corneal clouding in patients suffering from mucopolysaccharidosis with the Pentacam densitometry programme. Br J Ophthalmol. 2013 Jul;97(7):829-33. doi: 10.1136/bjophthalmol-2012-302913. Epub 2013 May 17.
- Background Pahuja N, Shetty R, Subbiah P, Nagaraja H, Nuijts RM, Jayadev C. Corneal Densitometry: Repeatability in Eyes With Keratoconus and Postcollagen Cross-Linking. Cornea. 2016 Jun;35(6):833-7. doi: 10.1097/ICO.0000000000000800.
- Background Akkaya Turhan S, Toker E. Changes in Corneal Density After Accelerated Corneal Collagen Cross-linking With Different Irradiation Intensities and Energy Exposures: 1-Year Follow-up. Cornea. 2017 Nov;36(11):1331-1335. doi: 10.1097/ICO.0000000000001362.
- Background Enders P, Holtick U, Schaub F, Tuchscherer A, Hermann MM, Scheid C, Cursiefen C, Bachmann BO. Corneal Densitometry for Quantification of Corneal Deposits in Monoclonal Gammopathies. Cornea. 2017 Apr;36(4):470-475. doi: 10.1097/ICO.0000000000001078.
- Background Gutierrez R, Lopez I, Villa-Collar C, Gonzalez-Meijome JM. Corneal transparency after cross-linking for keratoconus: 1-year follow-up. J Refract Surg. 2012 Nov;28(11):781-6. doi: 10.3928/1081597X-20121011-06.
- Background Greenstein SA, Fry KL, Bhatt J, Hersh PS. Natural history of corneal haze after collagen crosslinking for keratoconus and corneal ectasia: Scheimpflug and biomicroscopic analysis. J Cataract Refract Surg. 2010 Dec;36(12):2105-14. doi: 10.1016/j.jcrs.2010.06.067.
- Background Weiner X, Baumeister M, Kohnen T, Buhren J. Repeatability of lens densitometry using Scheimpflug imaging. J Cataract Refract Surg. 2014 May;40(5):756-63. doi: 10.1016/j.jcrs.2013.10.039.
- Background Kim BZ, Jordan CA, McGhee CN, Patel DV. Natural history of corneal haze after corneal collagen crosslinking in keratoconus using Scheimpflug analysis. J Cataract Refract Surg. 2016 Jul;42(7):1053-9. doi: 10.1016/j.jcrs.2016.04.019.
- Background Boulze-Pankert M, Dariel R, Hoffart L. Corneal Scheimpflug Densitometry Following Photorefractive Keratectomy in Myopic Eyes. J Refract Surg. 2016 Nov 1;32(11):788-791. doi: 10.3928/1081597X-20160720-02.
- Background McLaren JW, Wacker K, Kane KM, Patel SV. Measuring Corneal Haze by Using Scheimpflug Photography and Confocal Microscopy. Invest Ophthalmol Vis Sci. 2016 Jan 1;57(1):227-35. doi: 10.1167/iovs.15-17657.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Allogeneic Mesenchymal Stromal Cells | Cell therapy | 1e+06 cells | Other |
| Comparator | Allogeneic Mesenchymal Stromal Cells | Cell therapy | 3e+06 cells | Other |
| Comparator | Allogeneic Mesenchymal Stromal Cells | Cell therapy | 6e+06 cells | Other |