Corneal Nerves After Treatment With Cenegermin

Neurotrophic Keratitis Clinical Trial

Official title:

Structural and Functional Changes of Corneal Innervation After Treatment With Cenegermin

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04627571
• Other study ID #: 20-000833
• Status: Recruiting
• Start date: May 23, 2022
• Est. completion date: December 2024

Study information

• Verified date: November 2023
• Source: University of California, Los Angeles
• Contact: Simon Fung, MD
• Phone: 310-794-9581
• Email: simonfung[@]mednet.ucla.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Neurotrophic keratopathy (NK) is a condition in which patients have fewer or complete absence of nerves in the cornea, characterized by the reduced or absent corneal sensation. The lack of nerves in the cornea also result in damages of the cornea and in severe situation the loss of the eye. Cenegermin (trade name Oxervate) is a nerve growth factor eye drops designed to treat NK, and currently, it is the only FDA-approved medication for this purpose. Even though cenegermin is effective in the majority of patients, there is a lack of understanding of how cenegermin works in the eye. In this study, investigators aim to determine the structural and functional effects of cenegermin on the cornea, using non-invasive technologies including in vivo confocal microscopy on study participants with NK over the course of a year.

Description:

Cenegermin (OxervateTM) is a recombinant human form of nerve growth factor developed by Dompé Farmaceutici S.p.A. for patients who are diagnosed with corneal epithelial defects due to moderate to severe stages of NK.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria

1. Patients =18 years of age; AND

2. Persistent corneal epitheliopathy that is refractory to treatments for =2 weeks; AND

3. Evidence of decreased corneal sensitivity, defined as =45mm on Cochet-Bonnet esthesiometer, within the area of the persistent corneal epitheliopathy; AND

4. Evidence of decreased corneal sensitivity, defined as above, in =1 corneal quadrant outside the persistent corneal epithelial defect. Exclusion Criteria

1. Patients with severe neurotrophic keratopathy characterized by corneal stromal ulceration involving over 75% of the total central corneal thickness and impending perforation.

2. Patients who have used cenegermin eyedrops, autologous serum eyedrops, plasma-rich plasma eyedrops, or umbilical cord eyedrops for the treatment of neurotrophic keratopathy 8 weeks prior to study recruitment.

3. Corneal surgery (including keratoplasty or refractive surgical procedures) within three months before study enrollment.

4. Presence of concurrent bacterial or fungal infection.

Related Conditions & MeSH terms

• Keratitis
• Neurotrophic Keratitis

Intervention

Drug:
• Cenegermin Ophthalmic Solution [Oxervate]
An 8-week course of topical cenegermin eye drops given 6 times daily would be started in the affected eye, in conjunction with the pre-existing medical treatment for neurotrophic keratopathy. Patients will be followed-up at 4 weeks, 6 weeks, 8 weeks, 3 months, 6 months, 9 months and 12 months (±2 weeks at each time point) after treatment. At each visit, patients will be assessed to determine the corneal epithelial defect and corneal sensation.

Locations

Country	Name	City	State
United States	University of California, Los Angeles	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (7)

Bonini S, Lambiase A, Rama P, Caprioglio G, Aloe L. Topical treatment with nerve growth factor for neurotrophic keratitis. Ophthalmology. 2000 Jul;107(7):1347-51; discussion 1351-2. doi: 10.1016/s0161-6420(00)00163-9. — View Citation

Bonini S, Lambiase A, Rama P, Filatori I, Allegretti M, Chao W, Mantelli F; REPARO Study Group. Phase I Trial of Recombinant Human Nerve Growth Factor for Neurotrophic Keratitis. Ophthalmology. 2018 Sep;125(9):1468-1471. doi: 10.1016/j.ophtha.2018.03.004. Epub 2018 Apr 10. No abstract available. — View Citation

Lambiase A, Sacchetti M, Bonini S. Nerve growth factor therapy for corneal disease. Curr Opin Ophthalmol. 2012 Jul;23(4):296-302. doi: 10.1097/ICU.0b013e3283543b61. — View Citation

Mastropasqua L, Lanzini M, Dua HS, D' Uffizi A, Di Nicola M, Calienno R, Bondi J, Said DG, Nubile M. In Vivo Evaluation of Corneal Nerves and Epithelial Healing After Treatment With Recombinant Nerve Growth Factor for Neurotrophic Keratopathy. Am J Ophthalmol. 2020 Sep;217:278-286. doi: 10.1016/j.ajo.2020.04.036. Epub 2020 May 6. — View Citation

Pflugfelder SC, Massaro-Giordano M, Perez VL, Hamrah P, Deng SX, Espandar L, Foster CS, Affeldt J, Seedor JA, Afshari NA, Chao W, Allegretti M, Mantelli F, Dana R. Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy: A Multicenter Randomized Vehicle-Controlled Pivotal Trial. Ophthalmology. 2020 Jan;127(1):14-26. doi: 10.1016/j.ophtha.2019.08.020. Epub 2019 Aug 26. — View Citation

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. — View Citation

Ting DSJ. Re: Bonini et al.: Phase 2 randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis (Ophthalmology. 2018;125:1332-1343). Ophthalmology. 2019 Feb;126(2):e14-e15. doi: 10.1016/j.ophtha.2018.09.017. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Presence/absence of Changes in Dry Eye Symptom	To determine changes in dry eye symptom scores assessed by the Ocular Surface Disease Index in patients initiated on cenegermin for recalcitrant neurotrophic keratopathy. A score ranges from 0 to 100 with scores 0 to 12 representing normal, 13 to 22 representing mild dry eye disease, 23 to 32 representing moderate dry eye disease, and greater than 33 representing severe dry eye disease.	1 year
Other	Changes in Tear Production	To determine the changes in tear production in patients initiated on cenegermin for recalcitrant neurotrophic keratopathy.	1 year
Other	Changes in Tear Characteristics	To determine the changes in tear film osmolarity in patients initiated on cenegermin for recalcitrant neurotrophic keratopathy.	1 year
Primary	Change in corneal nerve fiber density (CNFD)	To determine the changes in corneal nerve fiber density (CNFD), assessed by in vivo confocal microscopy.	1 year
Secondary	Duration of changes in CNFD	To determine the duration of the changes in corneal nerve fiber density (CNFD), assessed by in vivo confocal microscopy.	1 year

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