Phase I Study of Ciliary Neurotrophic Factor (CNF) Delivered by Intravitreal Implant of Encapsulated Cell Technology (ECT) Device in Patients With Retinitis Pigmentosa

Abstract

Abstract: : Purpose: To conduct a Phase I clinical trial to investigate the safety of CNTF delivered by encapsulated cell technology (ECT) through intravitreal implant in patients with retinitis pigmentosa. Methods: CNTF was delivered to the human eye by cells genetically engineered to produce CNTF and then encapsulated in a small device that is surgically implanted into the vitreous through the pars plana of one eye for each subject. ECT implant devices were provided by Neurotech USA. The current ECT device measures 6.5 mm in length and 1 mm in diameter with a titanium loop. Study design was open label, and neither subjects nor investigators were masked. The study includes 10 subjects, two CNTF dosages with 5 subjects per group. Inclusion criteria included visual acuity < 20/100, central visual field diameter of < 40 degrees, and flicker ERG amplitude < 2µV. Study duration was 6 months, and all devices were retrieved from the patients at the end of the study. The study is being monitored by an independent Data and Safety Monitoring Committee. Results: As of abstract submission, 6 of the 10 subjects have completed the study and the devices have been explanted. Results thus far indicate no concerns regarding safety of the molecule delivered in the dosages or in the devices themselves. Conclusions: In more than a decade of work by many laboratories, CNTF has been shown effective in retarding photoreceptor degeneration in 13 rodent and canine models, including naturally–occurring and laboratory–created genetic models and in environmental light–damage models. To date, the ECT method of CNTF delivery to the human eye appears safe. This first phase of a clinical study of CNTF for human retinal degeneration is nearing completion, all devices will be explanted by April 2005, and the outcome results will be discussed.

Keywords: clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled • neuroprotection • retinal degenerations: hereditary