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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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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.
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.
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.
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.
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