Safety and Efficacy of the PAINLESS Nerve Growth Factor CHF6467 in Optic Pathway Glioma (OPG)

Infantile optic pathway glioma (OPG) is generally benign and slow-growing, but due to infiltration and compression of sensitive neuronal structures in the optical pathways, progressive visual loss is a frequent and highly debilitating complication of the condition. Recently, therapeutic strategies aimed at neuroprotection in the visual pathway rather than reducing the size of the tumor have been studied. Nerve growth factor (NGF) is a neurotrophin that acts on peripheral and central neurons by binding with high affinity to the trkANGFR receptor, which has tyrosine kinase activity, and with low affinity to the non-selective pan-neurotrophin receptor p75NTR that regulates signaling through trkANGFR. The effect of NGF on target cells depends on the ratio of these two co-distributed receptors on the cell surface. Recently, two studies have shown that murine NGF can prevent progression of visual damage in OPG patients. These successful exploratory studies (the last of which was a randomized, double-blind, placebo-controlled study) represent a significant reference point in the field of vision loss in OPG patients and provide the basis and rationale for this study using a recombinant form of mutated NGF, painless NGF (CHF6467), which is anticipated to prove devoid of adverse effects related to pain at therapeutic doses. The purpose of this randomised study is to assess the safety and efficacy of multiple doses of painless NGF CHF6467 eye drops on the visual function of children or young adults with optic pathway gliomas, whether or not associated with type 1 neurofibromatosis. This study will include serial assessments of both optical pathway functionality and morphology, using electrophysiological and magnetic resonance imaging (MRI) techniques of the brain. The comparator will be a placebo preparation based on a physiologically balanced salt solution. This comparator has no effect on retinal function and optic nerve, is painless and perfectly tolerated, as reported by numerous clinical studies including that of our group.

Sex

All

Minimum age

3 Years

Maximum age

40 Years

Inclusion Criteria:

\- 1. Paediatric or adult subjects between the ages of 3 and 40 (including extremes).

2\. Diagnosis of OPG-induced visual damage, with or without type 1 neurofibromatosis (NF-1) 3. Stable disease with two brain MRI checks, performed at least 6 months before screening.

Exclusion Criteria:

\- 1. concomitant ophthalmological disorder that may affect electrophysiological evaluation.

2\. radiotherapy or chemotherapy or any other specific antineoplastic treatment within 9 months before entry.

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