Clinical trial NCT04627571: Corneal Nerves After Treatment With Cenegermin
Official title: Structural and Functional Changes of Corneal Innervation After Treatment With Cenegermin
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neurotrophic Keratitis
Keywords: cenegermin
neurotrophic keratopathy
corneal nerve
corneal sensation
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: Dompé Farmaceutici S.p.A
First posted: 2020-11-13
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients who are 18 years of age or older, who have a persistent corneal epitheliopathy due to neurotrophic keratopathy that is refractory to conventional non-surgical treatments for 2 weeks or more, and who fulfill the inclusion and exclusion criteria detailed above.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in corneal nerve fiber density (CNFD)
timeFrame: 1 year
Secondary outcomes:
measure: Duration of changes in CNFD
timeFrame: 1 year
Other outcomes:
measure: Presence/absence of Changes in Dry Eye Symptom
timeFrame: 1 year
measure: Changes in Tear Production
timeFrame: 1 year
measure: Changes in Tear Characteristics
timeFrame: 1 year
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
Study officials:
References:
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.
citation: 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.
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.
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.
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.
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.
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.