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Ronald Buggage, Pier Ruffini, Mauro Ferrari; Phase I, Randomized, Double-Masked, Vehicle-Controlled Study to Evaluate Safety, Tolerability and Pharmacokinetics of Recombinant Human Nerve Growth Factor Eye Drops in Healthy Volunteers. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1944.
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Nerve growth factor, an endogenous protein involved in the differentiation and maintenance of neurons, is a potential treatment for ocular neurodegenerative conditions. A clinical trial evaluating the safety of a topical ophthalmic formulation of recombinant human nerve growth factor (rhNGF) in normal subjects was conducted.
Healthy adult volunteers with no notable ocular/medical history and having normal ophthalmic and general examinations at screening and baseline were enrolled and assigned to 1 of 3 study phases. In Part 0, 1 eye received a single administration of rhNGF 0.5, 5 or 20 µg/ml. In Part A, 1 drop of rhNGF 20, 60 or 180 µg/ml or vehicle was administered to 1 eye every 4 hours for 1 day while in Part B, the same dose regimens or vehicle was administered to 1 eye daily for 5 days. In all phases treatment was randomized and the fellow eye received a matching vehicle regimen. Safety evaluations included a complete ophthalmic exam, ECG, vital signs, urinalysis and routine labs. Plasma samples for pharmacokinetics and immnogenicity were obtained in parts A and B.
Parts 0, A and Part B first cohort have been completed with 45/73 subjects treated with rhNGF. Masked review of all available safety information reveals good tolerability to the study medication with no clinically significant ocular or systemic changes observed. Ocular adverse events (AEs), generally transient and mild, included warm feeling, pressure, hazy film, increased corneal fluorescein staining, blurred vision, upper eyelid burning, headache above the eyes, photophobia, itching and loss of color distinction. In 3/8 subjects the AEs affected both eyes. 8 subjects reported non-ocular AEs not related to the study treatment. No serious adverse events were recorded.
NGF is a promising therapy for neurotrophic keratitis, retinitis pigmentosa and optic neuropathies, ocular neurodegenerative diseases for which no effective treatments currently exist. Early findings from a first in human trial evaluating a topical ophthalmic formulation of rhNGF suggest no local or systemic safety concerns. Unmasked data including pharmacokinetic analysis and immunogenicity will be presented to complete the safety profile of rhNGF in healthy volunteers.
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