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

Byron L Lam, Janet L Davis, Ninel Gregori, Robert E. MacLaren, Aniz Girach, Jennifer D. Verriotto, Belen Rodriguez, Potyra R. Rosa, Xiaojun Zhang, William J Feuer

Research output: Contribution to journalArticle

Abstract

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 (1011 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.

LanguageEnglish (US)
Pages65-73
Number of pages9
JournalAmerican journal of ophthalmology
Volume197
DOIs
StatePublished - Jan 1 2019

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Choroideremia
Genetic Therapy
Clinical Trials
Optical Coherence Tomography
Visual Acuity
Retinal Perforations
Virus Shedding
Safety
Injections
Body Fluids
Antibody Formation
Maintenance

ASJC Scopus subject areas

  • Ophthalmology

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Choroideremia Gene Therapy Phase 2 Clinical Trial : 24-Month Results. / Lam, Byron L; Davis, Janet L; Gregori, Ninel; MacLaren, Robert E.; Girach, Aniz; Verriotto, Jennifer D.; Rodriguez, Belen; Rosa, Potyra R.; Zhang, Xiaojun; Feuer, William J.

In: American journal of ophthalmology, Vol. 197, 01.01.2019, p. 65-73.

Research output: Contribution to journalArticle

Lam, Byron L ; Davis, Janet L ; Gregori, Ninel ; MacLaren, Robert E. ; Girach, Aniz ; Verriotto, Jennifer D. ; Rodriguez, Belen ; Rosa, Potyra R. ; Zhang, Xiaojun ; Feuer, William J. / Choroideremia Gene Therapy Phase 2 Clinical Trial : 24-Month Results. In: American journal of ophthalmology. 2019 ; Vol. 197. pp. 65-73.
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AU - Verriotto, Jennifer D.

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