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

Am J Ophthalmol. 2019 Jan:197:65-73. doi: 10.1016/j.ajo.2018.09.012. Epub 2018 Sep 19.


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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Choroideremia / physiopathology
  • Choroideremia / therapy*
  • Contrast Sensitivity / physiology
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Humans
  • Male
  • Middle Aged
  • Tomography, Optical Coherence
  • Visual Acuity / physiology
  • Visual Fields / physiology