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

NCT05733572 | Active Not Recruiting Phase 2

• 1 other identifier: CHF6467-OPG
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Optic Pathway Glioma

Keywords

Optic pathway glioma, nerve growth factor; optic atrophy

Outcome Measures

Primary Outcomes (1)

• visual field

  : the largest radius (the largest) of the field of view measured in degrees of visual angle by kinetic perimetry according to Goldmann with the aim V/4e.

  6 months

Secondary Outcomes (1)

• visual evoked potentials

  6 months

Study Arms (2)

active treatment group

EXPERIMENTAL

active drug treatment group

Drug: CHF6467

placebo group

PLACEBO COMPARATOR

pacebo group

Drug: Placebo

Interventions

CHF6467 DRUG

drug eyedrops

Also known as: painless NGF

active treatment group

Placebo DRUG

placebo eyedrops

placebo group

Eligibility Criteria

• Age: 3 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• \- 1. concomitant ophthalmological disorder that may affect electrophysiological evaluation.
• \. radiotherapy or chemotherapy or any other specific antineoplastic treatment within 9 months before entry.

Sponsors & Collaborators

• Benedetto Falsini: lead

Study Sites (1)

Catholic University, Policlinico A. Gemelli (Hospital)

Rome, 00168, Italy

Location

Related Publications (4)

• Falsini B, Chiaretti A, Rizzo D, Piccardi M, Ruggiero A, Manni L, Soligo M, Dickmann A, Federici M, Salerni A, Timelli L, Guglielmi G, Lazzareschi I, Caldarelli M, Galli-Resta L, Colosimo C, Riccardi R. Nerve growth factor improves visual loss in childhood optic gliomas: a randomized, double-blind, phase II clinical trial. Brain. 2016 Feb;139(Pt 2):404-14. doi: 10.1093/brain/awv366. Epub 2016 Jan 14.

  PMID: 26767384 RESULT

• Falsini B, Chiaretti A, Barone G, Piccardi M, Pierri F, Colosimo C, Lazzareschi I, Ruggiero A, Parisi V, Fadda A, Balestrazzi E, Riccardi R. Topical nerve growth factor as a visual rescue strategy in pediatric optic gliomas: a pilot study including electrophysiology. Neurorehabil Neural Repair. 2011 Jul-Aug;25(6):512-20. doi: 10.1177/1545968310397201. Epub 2011 Mar 26.

  PMID: 21444653 RESULT

• Chiaretti A, Falsini B, Servidei S, Marangoni D, Pierri F, Riccardi R. Nerve growth factor eye drop administration improves visual function in a patient with optic glioma. Neurorehabil Neural Repair. 2011 May;25(4):386-90. doi: 10.1177/1545968310395601. Epub 2011 Feb 22.

  PMID: 21343523 RESULT

• Abed E, Corbo G, Falsini B. Neurotrophin family members as neuroprotectants in retinal degenerations. BioDrugs. 2015 Feb;29(1):1-13. doi: 10.1007/s40259-014-0110-5.

  PMID: 25408174 RESULT

MeSH Terms

Conditions

Hereditary Sensory and Autonomic Neuropathies; Optic Atrophy

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases

Study Officials

• Benedetto Falsini, MD

  universita Cattolica del S. Cuore/Fondazione policlinico A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double masking (patients and outcome assessors)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: This is a phase 2a study intended to demonstrate the superiority over placebo of 10 days' treatment with CHF6467 in significantly improving the field of vision of children and young adults with optical pathway glioma, 12 weeks after the start of treatment.

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: February 17, 2023
• Study Start: June 12, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 24 months

Locations

IT (1)