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Francesco Sinigaglia, ; Phase I/II Dose-Ranging, Randomized Clinical Trial of Recombinant Human Nerve Growth Factor in the Treatment of Neurotrophic Keratitis: Preliminary Results. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4690.
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Open, uncontrolled studies showed that Nerve Growth Factor (NGF) is an effective treatment in patients with neurotrophic corneal ulcers. A randomized, controlled trial evaluating the safety and efficacy of recombinant human NGF (rhNGF) eye drops in patients with neurotrophic keratitis (NK) is being conducted and preliminary results of the phase I segment of the study are presented.
A multicenter, randomized, double-masked, placebo-controlled Phase I/II study is being conducted in 174 subjects with corneal epithelial defect (PED) or corneal ulcer. Eligible NK subjects were randomized 7: 7: 2 in the phase I (18 subjects) and 1:1:1 in the phase II segment of the study to rhNGF (10 and 20 µg/ml) or vehicle eye drops administered 6 times a day for 8 weeks. Primary outcome of phase I is safety and tolerability. Efficacy endpoints include healing of PED, corneal sensitivity and tear function tests. Masked statistical analyses of phase I data were performed considering group A (7 treated with rhNGF 10 µg/ml and 2 with vehicle) and group B (7 treated with rhNGF 20 µg/ml and 2 with vehicle).
18 patients (7 males, 11 females, mean age of 62) with NK caused by diabetes (4), previous ocular surgeries (4), ocular herpes zoster (2) or simplex (3) infection, neurosurgery (3), others (2) were included in the study. No significant changes of vital signs and blood values were observed during treatment. Thirty-seven adverse events (AEs) were recorded and 3 required discontinuation of study drug (2 in group A and 1 un group B). Thirteen AEs were possibly related to the study drug. Among the 5 serious AEs observed, only 1 (enlargement of PED) was possibly related to the study drug. Visual acuity was decreased in 2 patients, and ameliorated in 11 at the end of treatment. Treatment was well tolerated according to VAS scores. Corneal lesions completely healed in 73% (71% in group A and 75% in group B), corneal sensitivity increased in 33% in both groups and Schirmer values increased in 39% of the patients (33% in group A and 44% in group B).
These initial results show that rhNGF eye drop is safe and well-tolerated. No significant systemic or ophthalmic complications were observed. Phase II results will be available to establish the efficacy and the dose response of rhNGF eye drops treatment in NK patients.
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