Randomized trial of ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for retinitis pigmentosa

Am J Ophthalmol. 2013 Aug;156(2):283-292.e1. doi: 10.1016/j.ajo.2013.03.021. Epub 2013 May 10.

Abstract

Purpose: To evaluate the safety and effect on visual function of ciliary neurotrophic factor delivered via an intraocular encapsulated cell implant for the treatment of retinitis pigmentosa (RP).

Design: Ciliary neurotrophic factor for late-stage retinitis pigmentosa study 3 (CNTF3; n = 65) and ciliary neurotrophic factor for early-stage retinitis pigmentosa study 4 (CNTF4; n = 68) were multicenter, sham-controlled dose-ranging studies.

Methods: Patients were randomly assigned to receive a high- or low-dose implant in 1 eye and sham surgery in the fellow eye. The primary endpoints were change in best-corrected visual acuity (BCVA) at 12 months for CNTF3 and change in visual field sensitivity at 12 months for CNTF4. Patients had the choice of retaining or removing the implant at 12 months for CNTF3 and 24 months for CNTF4.

Results: There were no serious adverse events related to either the encapsulated cell implant or the surgical procedure. In CNTF3, there was no change in acuity in either ciliary neurotrophic factor- or sham-treated eyes at 1 year. In CNTF4, eyes treated with the high-dose implant showed a significant decrease in sensitivity while no change was seen in sham- and low dose-treated eyes at 12 months. The decrease in sensitivity was reversible upon implant removal. In both studies, ciliary neurotrophic factor treatment resulted in a dose-dependent increase in retinal thickness.

Conclusions: Long-term intraocular delivery of ciliary neurotrophic factor is achieved by the encapsulated cell implant. Neither study showed therapeutic benefit in the primary outcome variable.

Trial registration: ClinicalTrials.gov NCT00447980 NCT00447993.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Ciliary Neurotrophic Factor / administration & dosage*
  • Ciliary Neurotrophic Factor / adverse effects
  • Drug Delivery Systems*
  • Drug Implants
  • Electroretinography
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Middle Aged
  • Retina / physiopathology
  • Retinitis Pigmentosa / drug therapy*
  • Retinitis Pigmentosa / physiopathology
  • Tomography, Optical Coherence
  • Visual Acuity / physiology
  • Visual Fields / physiology
  • Young Adult

Substances

  • Ciliary Neurotrophic Factor
  • Drug Implants

Associated data

  • ClinicalTrials.gov/NCT00447980
  • ClinicalTrials.gov/NCT00447993