July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
CEP290-associated LCA due to a photoreceptor cilium defect treated with an intravitreal antisense oligonucleotide results in improved vision
Author Affiliations & Notes
  • Artur V Cideciyan
    Dept of Ophthalmology, Scheie Eye Institute, Univ of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Samuel G Jacobson
    Dept of Ophthalmology, Scheie Eye Institute, Univ of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Arlene V Drack
    Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Allen C Ho
    Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, United States
  • Alexandra Garafalo
    Dept of Ophthalmology, Scheie Eye Institute, Univ of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Alejandro J Roman
    Dept of Ophthalmology, Scheie Eye Institute, Univ of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Mike Schwartz
    ProQR Therapeutics, Netherlands
  • Patricia Biasutto
    ProQR Therapeutics, Netherlands
  • Wilma de Wit
    ProQR Therapeutics, Netherlands
  • Michael E Cheetham
    UCL Institute of Ophthalmology, London, United Kingdom
  • Peter S Adamson
    ProQR Therapeutics, Netherlands
    UCL Institute of Ophthalmology, London, United Kingdom
  • David Rodman
    ProQR Therapeutics, Netherlands
  • Julie De Zaeytijd
    Department of Ophthalmology, Ghent University and Ghent University Hospital, Ghent, Belgium
  • Caroline Van Cauwenbergh
    Department of Ophthalmology, Ghent University and Ghent University Hospital, Ghent, Belgium
  • Bart P Leroy
    Department of Ophthalmology, Ghent University and Ghent University Hospital, Ghent, Belgium
    Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium
  • Stephen R Russell
    Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Footnotes
    Commercial Relationships   Artur Cideciyan, ProQR (F); Samuel Jacobson, None; Arlene Drack, None; Allen Ho, None; Alexandra Garafalo, None; Alejandro Roman, None; Mike Schwartz, ProQR (E); Patricia Biasutto, ProQR (E); Wilma de Wit, ProQR (E); Michael Cheetham, ProQR (C); Peter Adamson, ProQR (E); David Rodman, ProQR (E); Julie De Zaeytijd, None; Caroline Van Cauwenbergh, None; Bart Leroy, ProQR (F); Stephen Russell, ProQR (F)
  • Footnotes
    Support  ProQR Therapeutics
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1834. doi:https://doi.org/
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    • Get Citation

      Artur V Cideciyan, Samuel G Jacobson, Arlene V Drack, Allen C Ho, Alexandra Garafalo, Alejandro J Roman, Mike Schwartz, Patricia Biasutto, Wilma de Wit, Michael E Cheetham, Peter S Adamson, David Rodman, Julie De Zaeytijd, Caroline Van Cauwenbergh, Bart P Leroy, Stephen R Russell; CEP290-associated LCA due to a photoreceptor cilium defect treated with an intravitreal antisense oligonucleotide results in improved vision. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1834. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To assess safety and efficacy of the antisense oligonucleotide (QR-110) in LCA10 patients carrying the c.2991+1655A>G allele in the ciliopathy gene CEP290.

Methods : In a three-center open-label clinical trial (NCT03140969), subjects received intravitreal injections of QR-110 in the worse seeing eye every three months. There were two combinations of loading/maintenance doses: 160/80 µg or 320/160 µg. Systemic and ocular safety was evaluated with standard methods. Efficacy was evaluated with visual acuity (VA), oculomotor control and instability (OCI), two-color full-field stimulus test (FST), and mobility course testing among others. In a patient with an exceptional response, additional specialized tests of visual function were performed. Study was planned for 4 injections over one year but based on exceptional results in one patient, an interim analysis was performed with the data cutoff date of Aug 2018.

Results : Ten patients received at least 1 and up to 4 injections, and were followed for at least 1 and up to 9 months. At 3 months after the first (loading) injection, treated eyes were significantly improved compared to baseline by an average of 0.67 log (7 lines) in VA (P=0.022), 0.62 log in red FST (P=1E-6), and 0.81 log in blue FST (P<2E-16). At 3 months after the second (maintenance) injection, VA and FST results remained improved, and OCI results also demonstrated greater stability. Exceptional responder showed a VA improvement from light perception to 20/400, and large improvements in FST. Removing the exceptional responder from the analyses did not change the main statistical conclusion supporting significant improvements of vision at 3 months. Adverse events included cystoid macular edema and subcapsular cataract.

Conclusions : Preliminary results with QR-110 support an acceptable safety profile and potential for improvement of visual acuity and light sensitivity. Safety of the drug, and the efficacy and durability of the effect continue to be evaluated.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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