Study Objectives
The poster presented during the EuCornea Congress describes the preliminary results of the Phase I segment of the REPARO Study, a randomized, double-masked, placebo controlled Phase I/II clinical trial. The Phase II segment of the study is currently underway at 39 sites in 9 European countries, and is intended to evaluate the safety, efficacy, and dose-response of treatment with rhNGF eye drops in patients with stage 2 (persistent epithelial defect) or stage 3 (corneal ulcer) neurotrophic keratitis that did not respond to the non-surgical medical treatments currently available.
General Aspects of the Research Protocol
Eighteen subjects were involved in the Phase I segment of the study. These subjects were administered either rhNGF in the form of eye drops at two different dosages (10 or 20 µg/ml), or eye drops containing the placebo. Treatment was repeated six times per day for eight weeks. The primary endpoint of the study was the evaluation of safety and tolerability of the treatment, and secondary objectives included corneal wound closure, in addition to the improvement of visual acuity and corneal sensitivity.
The Phase II segment of the REPARO study, currently underway, provides for the recruitment of another 156 patients, divided according to the aforementioned treatment scheme. Currently, the study is in an advanced stage of the enrollment process, with over 90 patients enrolled. The primary endpoint of the trial is to evaluate the complete corneal healing.
Other objectives of the study include assessment of the level of corneal sensitivity, visual acuity, tear function, and efficacy of the treatment over time.
rhNGF recently received the designation of an orphan drug for the treatment of neurotrophic keratitis by the American regulatory agency, the FDA.
It is anticipated that rhNGF will be studied over the next few months for the same pathology in centers of excellence in the treatment of corneal pathologies in the United States.
The Main Results
Although the data is still masked (meaning that it is not yet possible to know which patients received rhNGF and which patients received the placebo), the data from the Phase I segment of the REPARO study show a good safety and tolerability profile among patients affected by neurotrophic keratitis. Administration of rhNGF or the placebo, in fact, did not lead to any significant systemic or ocular side effects.
A considerable reduction of symptoms associated with neurotrophic keratitis was observed in the VAS score, such as blurred vision (-24%), burning (-16%), foreign body sensation (-9%), itching (-8%), and photophobia (-14%).
Furthermore, in 73 percent of patients treated, complete closure of the corneal wound was observed, which in one out of three cases was associated with improvement of the sensitivity of the cornea. It took less time for the corneal wound to heal in the group that was treated with the highest concentration of rhNGF.
Finally, it was confirmed that the patients who showed a progression in the size of the corneal wound, during the Phase I segment as well as during the course of the Phase II segment of the study, had been treated with the placebo.
What Does the Available Data Reveal?
The study demonstrates the safety and tolerability of treatment with rhNGF for ophthalmic use, without significant systemic or ophthalmic complications. The first observations, although they are of a preliminary nature, also provide encouraging indications in terms of efficacy. In order to have reliable data on efficacy, however, it would be necessary to have the full results from the study currently underway, after enrollment has been completed and the data related to the patients treated has been analyzed.
About rhNGF
rhNGF, the recombinant human Nerve Growth Factor developed by Dompé, is identical to the protein naturally produced by the body, and promotes the development and survival of nerve cells, including those of the retina. NGF (Nerve Growth Factor) was discovered by Rita Levi Montalcini, who was awarded the Nobel Prize for Medicine and Physiology in 1986 for her work. The protein stimulates the growth, maintenance, and survival of nerve cells, in addition to the cells of the cornea and the retina. The cornea, in particular, has a dense innervation, approximately 400 times denser than that of the skin. Treatment with a rhNGF-based ophthalmic solution aims to restore the corneal innervation that has been compromised by the disease in order to promote recovery of visual function. In the future, rhNGF may also prove useful in treating other forms of ophthalmic diseases, as it has for retinitis pigmentosa or in the treatment of glaucoma and dry eye syndrome due to its innovative mechanism of action.Neurotrophic Keratitis
Neurotrophic keratitis is a rare, serious degenerative disease of the eye, for which there is currently no cure, characterized by progressive damage to the cornea that can lead to corneal perforation with consequent loss of vision. Neurotrophic keratitis can be caused by various clinical ocular conditions, such as herpetic corneal infections (herpes zoster and simplex), eye surgeries, misuse of topical medications, use of contact lenses, and even systemic conditions, such as diabetes or vitamin A deficiency. It affects less than 1 in 5,000 people in the world.