Choroideremia Gene Therapy Phase 2 Clinical Trial: 24-Month Results.

Autor: Lam BL; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA. Electronic address: blam@med.miami.edu., Davis JL; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA., Gregori NZ; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA., MacLaren RE; Nuffield Laboratory of Ophthalmology University of Oxford, and Oxford NIHR Biomedical Research Centre, Oxford, United Kingdom., Girach A; Nightstar Therapeutics, London, United Kingdom., Verriotto JD; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA., Rodriguez B; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA., Rosa PR; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA., Zhang X; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA., Feuer WJ; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
Jazyk: angličtina
Zdroj: American journal of ophthalmology [Am J Ophthalmol] 2019 Jan; Vol. 197, pp. 65-73. Date of Electronic Publication: 2018 Sep 19.
DOI: 10.1016/j.ajo.2018.09.012
Abstrakt: Purpose: To report the final results of a phase 2 high-dose gene therapy clinical trial in choroideremia.
Methods: Design: Phase 2 clinical trial.
Participants: Six men (aged 32-72 years) with genetically-confirmed advanced choroideremia. Patients received subfoveal injection of AAV2-REP1 (10 11 genome particles in 0.1 mL) in the worse-sighted eye.
Outcome Measures: Primary measure was best-corrected visual acuity (BCVA) change from baseline in the treated eye compared to the untreated eye. Secondary endpoints included change from baseline in microperimetry, fundus autofluorescence, and spectral-domain optical coherence tomography (OCT). Safety evaluations included adverse events, viral shedding in body fluids, and vector antibody responses.
Results: Baseline mean ETDRS BCVA was 65.3 ± 8.8 (SD, range 56-77, 20/32-20/80) letters in the treated eyes and 77.0 ± 4.2 (69-81, 20/25-20/40) letters in the untreated eyes. At 2 years, 1 treated eye improved by 10 letters and another by 5 letters, while 1 untreated eye improved by 4 letters. All other eyes were within 2 letters of baseline. Baseline microperimetry sensitivities in the treated eyes were poor (1.2 ± 2.1 (0, 5.1) dB) and showed no significant change. No serious adverse event occurred. Two patients developed an atrophic retinal hole in a nonfunctioning macular area where baseline OCT showed preexisting thinning. Intraoperative microscope-integrated OCT allowed proper subretinal injection with avoidance of excessive foveal stretching and macular hole formation.
Conclusions: Sustained improvement or maintenance of BCVA is achievable in choroideremia with high-dose AAV2-REP1, indicating BCVA is a viable primary outcome in advanced choroideremia. Choroideremia gene therapy delivered with intraoperative OCT has a good safety profile.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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