Cultivated Autologous Oral Mucosal Epithelial Transplantation for the Treatment of Ocular Surface Diseases

Limbal Stem Cell Deficiency Clinical Trial

Official title:

Cultivated Autologous Oral Mucosal Epithelial Transplantation for the Treatment of Ocular Surface Diseases: Phase Ib Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02739113
• Other study ID #: 104-7758C
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: April 6, 2016
• Last updated: April 11, 2016
• Start date: January 2016
• Est. completion date: December 2019

Study information

• Verified date: April 2016
• Source: Chang Gung Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Earlier protocol for cultivated oral mucosal epithelial transplantation (COMET) requires trypsin/EDTA to isolate epithelial cells from tissue, and uses murine 3T3 cells as feeder cells, which results in biosafety concern. This study uses collagenase instead of trypsin/EDTA to isolate epithelial cells, and does not use 3T3 cells co-culture, so as to make an animal ingredient-free cell culture product. The purpose of the study is to evaluate the feasibility of the new protocol of COMET in clinical use.

Description:

When corneal epithelial stem cells are destroyed by severe trauma such as burn or autoimmune diseases, poor regeneration of corneal epithelium, persistent inflammatory reaction, neovascular ingrowth, and conjunctivalization may ensue, and seriously reduce the vision. In treating the diseased eye, when the other eye is healthy, limbal tissue containing corneal epithelial stem cells can be harvested for direct tissue transplantation, or ex vivo cultivation and expansion for several days before transplantation.

For patients with bilaterally damaged eyes, rejection rate in non-HLA matched allograft limbal stem cell transplantation is very high, in addition, adverse reaction to long-term immunosuppressive therapy may be life-threatening. Therefore, in 2004 Japanese researchers first proposed a novel technique to treat ocular surface diseases using cultivated autologous oral mucosal epithelial transplantation (COMET). From 2006 to 2009, investigators have also conducted a Phase I clinical trial approved by Taiwan FDA. In that Phase I trial, investigators have demonstrated efficacy of such cell therapy in promoting wound healing in patients with severe ocular surface burns (Ma DHK et al. Eye 2009; 23: 1442- 1450). Investigators have also identify long-term persistence of transplanted oral mucosal epithelial cells in the cornea (Chen HCJ et al. Invest Ophthalmol Vis Sci 2009;50:4660-4668), justifying this innovative surgical procedure as an effective alternative treatment modality.

However, in previous protocol, animal products such as fetal calf serum and 3T3 cell culture were used, raising the biosafety concern. For this, recently investigators have developed an animal ingredient-free cell culture protocol, and our protocol can meet the GTP standards, and has obtained the accreditation by Taiwan FDA and affiliated institutes. Therefore, the focus of current Phase Ib trial is to confirm the feasibility of following items:

1. To produce cell culture product not containing animal ingredient, so as to avoid zoonoses. The oral mucosal epithelial cells thus cultured are used for treating ocular surface diseases with limbal stem cell deficiency.

2. To reduce recurrence of corneal neovascularization after COMET, Bevacizumab (Avastin) is injected locally, so as to improve corneal transparency and visual acuity.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: December 2019
• Est. primary completion date: March 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Severe corneal epithelial deficiency

• Having favorable prognosis potential

• Normal of the intraocular pressure

• Normal of the light perception for the optic nerve

• No retinal diseases for the inflicted eyes

• No severe dry eye

Exclusion Criteria:

• Having unfavorable prognosis potential

• Severe systemic disorders

• Unable to use daily vision

• Mentally retarded to execute permit on surgery

• Pregnant woman

Related Conditions & MeSH terms

• Limbal Stem Cell Deficiency

Intervention

Biological:
• Cultivated oral mucosal epithelial cell
Cell therapy for treating severe limbal stem cell deficiency using cultivated autologous oral mucosal epithelial cells.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

References & Publications (11)

Chen HC, Chen HL, Lai JY, Chen CC, Tsai YJ, Kuo MT, Chu PH, Sun CC, Chen JK, Ma DH. Persistence of transplanted oral mucosal epithelial cells in human cornea. Invest Ophthalmol Vis Sci. 2009 Oct;50(10):4660-8. doi: 10.1167/iovs.09-3377. Epub 2009 May 20. — View Citation

Chen HC, Yeh LK, Tsai YJ, Lai CH, Chen CC, Lai JY, Sun CC, Chang G, Hwang TL, Chen JK, Ma DH. Expression of angiogenesis-related factors in human corneas after cultivated oral mucosal epithelial transplantation. Invest Ophthalmol Vis Sci. 2012 Aug 17;53(9 — View Citation

Inatomi T, Nakamura T, Koizumi N, Sotozono C, Yokoi N, Kinoshita S. Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation. Am J Ophthalmol. 2006 Feb;141(2):267-275. — View Citation

Inatomi T, Nakamura T, Kojyo M, Koizumi N, Sotozono C, Kinoshita S. Ocular surface reconstruction with combination of cultivated autologous oral mucosal epithelial transplantation and penetrating keratoplasty. Am J Ophthalmol. 2006 Nov;142(5):757-64. Epub — View Citation

Li W, Sabater AL, Chen YT, Hayashida Y, Chen SY, He H, Tseng SC. A novel method of isolation, preservation, and expansion of human corneal endothelial cells. Invest Ophthalmol Vis Sci. 2007 Feb;48(2):614-20. — View Citation

Ma DH, Kuo MT, Tsai YJ, Chen HC, Chen XL, Wang SF, Li L, Hsiao CH, Lin KK. Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn. Eye (Lond). 2009 Jun;23(6):1442-50. doi: 10.1038/eye.2009.60. Epub 2009 Apr 17. — View Citation

Nakamura T, Inatomi T, Sotozono C, Amemiya T, Kanamura N, Kinoshita S. Transplantation of cultivated autologous oral mucosal epithelial cells in patients with severe ocular surface disorders. Br J Ophthalmol. 2004 Oct;88(10):1280-4. — View Citation

Nakamura T, Takeda K, Inatomi T, Sotozono C, Kinoshita S. Long-term results of autologous cultivated oral mucosal epithelial transplantation in the scar phase of severe ocular surface disorders. Br J Ophthalmol. 2011 Jul;95(7):942-6. doi: 10.1136/bjo.2010 — View Citation

Petsoglou C, Balaggan KS, Dart JK, Bunce C, Xing W, Ali RR, Tuft SJ. Subconjunctival bevacizumab induces regression of corneal neovascularisation: a pilot randomised placebo-controlled double-masked trial. Br J Ophthalmol. 2013 Jan;97(1):28-32. doi: 10.11 — View Citation

Satake Y, Higa K, Tsubota K, Shimazaki J. Long-term outcome of cultivated oral mucosal epithelial sheet transplantation in treatment of total limbal stem cell deficiency. Ophthalmology. 2011 Aug;118(8):1524-30. doi: 10.1016/j.ophtha.2011.01.039. Epub 2011 — View Citation

Takeda K, Nakamura T, Inatomi T, Sotozono C, Watanabe A, Kinoshita S. Ocular surface reconstruction using the combination of autologous cultivated oral mucosal epithelial transplantation and eyelid surgery for severe ocular surface disease. Am J Ophthalmo — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Re-epithelialization of cornea		21 days
Secondary	Regression of corneal neovascularization: Final averaged length of corneal blood vessels less than 35% total corneal area occupied by blood vessels.		6-12 months
Secondary	Improvement of best corrected visual acuity: At least 2 lines of improvement.		3 months
Secondary	Improvement in corneal clarity (slit lamp examination): Improvement at least one grade.		3 months