March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Update on QLT091001 in Subjects with Leber Congenital Amaurosis (LCA) due to Lecithin:Retinol Acyltransferase (LRAT) or Retinal Pigment Epithelial 65 Protein (RPE65) mutations: Longer-term follow-up of subjects originally treated with 7-day therapy
Author Affiliations & Notes
  • Robert K. Koenekoop
    McGill Ocular Genetics Laboratory,
    McGill University Health Centre, Montreal, Quebec, Canada
  • Eunice Esteban
    Paediatric Ophthalmology,
    McGill University Health Centre, Montreal, Quebec, Canada
  • Leah Wood
    Paediatric Ophthalmology,
    McGill University Health Centre, Montreal, Quebec, Canada
  • Ruifang Sui
    Ophthalmology, Peking Union Med College Hosp, Beijing, China
  • Juliana M. Sallum
    Ophthalmology, UNIFESP, Sao Paulo, Brazil
  • Elias I. Traboulsi
    Center for Genetic Eye Diseases, Cole Eye Institute, Cleveland, Ohio
  • L I. van den Born
    Medical Retina, Rotterdam Eye Hospital, Rotterdam, The Netherlands
  • Ava K. Bittner
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland
  • Gislin Dagnelie
    Ophthal-Lions Vision Cntr, Johns Hopkins Univ, Baltimore, Maryland
  • David A. Saperstein
    Ophthalmology, Ophthalmology, Seattle, Washington
  • Footnotes
    Commercial Relationships  Robert K. Koenekoop, FFB-C, CIHR, NIH, Reseau, FRSQ (F), QLT Inc (C); Eunice Esteban, QLT In (C); Leah Wood, QLT Inc (C); Ruifang Sui, None; Juliana M. Sallum, None; Elias I. Traboulsi, None; L. I. van den Born, None; Ava K. Bittner, QLT Inc (C); Gislin Dagnelie, QLT Inc (C); David A. Saperstein, QLT Inc (C)
  • Footnotes
    Support  QLT Inc, Foundation Fighting Blindness Canada, CIHR, Reseau Vision, FRSQ
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 4642. doi:
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      Robert K. Koenekoop, Eunice Esteban, Leah Wood, Ruifang Sui, Juliana M. Sallum, Elias I. Traboulsi, L I. van den Born, Ava K. Bittner, Gislin Dagnelie, David A. Saperstein; Update on QLT091001 in Subjects with Leber Congenital Amaurosis (LCA) due to Lecithin:Retinol Acyltransferase (LRAT) or Retinal Pigment Epithelial 65 Protein (RPE65) mutations: Longer-term follow-up of subjects originally treated with 7-day therapy. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4642.

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

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Abstract

Purpose: : To assess the safety and efficacy of an oral synthetic cis-retinoid (QLT091001) in subjects with LCA due to mutations in the LRAT or RPE65 genes, a severe form of childhood visual impairment.

Methods: : This is ongoing follow-up of a Phase Ib open-label, proof-of-concept clinical trial to evaluate the safety and efficacy of 7 days of oral QLT091001 in subjects with LCA due to mutations in the RPE65 or LRAT genes. Primary visual function tests are ETDRS best-corrected visual acuity (BCVA) and Goldmann visual fields (GVFs). Complete ophthalmic and physical examinations, electrocardiograms, and laboratory blood work are completed before and after treatment at predetermined time points. Mutations were identified by Sanger sequencing, confirmed by a CLIA certified lab.

Results: : Fourteen subjects (ages 6-38 years) with LCA due to LRAT (N=7) or RPE65 (N=7) mutations have been enrolled; 8 subjects maintained longer-term improvements in one or both of GVF and BCVA after 7 days of treatment. In 12 of 17 eyes (6 of 9 subjects) with baseline GVFs up to 70° average diameter, clinically meaningful improvements in retinal area of 27%-180% were seen, averaged over time. Six subjects followed for 9-13 months showed sustained GVF improvements ranging between 40%-50% on average over time. Notable VA improvements were seen in 5 subjects, which, in 3 subjects were maintained up to ≥12 months beyond the end of treatment. Changes in fMRI in a cohort of 3 subjects suggest potential effects on the visual cortex. Some subjects reported meaningful improvements in activities of daily living (ADLs). There were no serious adverse events. Transient headache and photophobia were reported and reversible elevations in triglyceride levels and reduction in HDL were recorded.

Conclusions: : Longer-term follow-up of subjects originally treated with 7 days of oral QLT091001 showed vision improvements in 8 of 14 LCA subjects. QLT091001 was well tolerated and adverse events were transient and/or reversible. Dormant photoreceptors may be able to respond to external manipulation. Enrollment of RP subjects is ongoing and will be reported separately.

Clinical Trial: : http://www.clinicaltrials.gov NCT01014052

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