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

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

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)65-73
Number of pages9
JournalAmerican journal of ophthalmology
StatePublished - Jan 2019

ASJC Scopus subject areas

  • Ophthalmology


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