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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 65-73 |
| Number of pages | 9 |
| Journal | American Journal of Ophthalmology |
| Volume | 197 |
| DOIs | |
| State | Published - Jan 1 2019 |
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ASJC Scopus subject areas
- Ophthalmology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Choroideremia Gene Therapy Phase 2 Clinical Trial
T2 - 24-Month Results
AU - Lam, Byron L
AU - Davis, Janet L
AU - Gregori, Ninel
AU - MacLaren, Robert E.
AU - Girach, Aniz
AU - Verriotto, Jennifer D.
AU - Rodriguez, Belen
AU - Rosa, Potyra R.
AU - Zhang, Xiaojun
AU - Feuer, William J
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajo.2018.09.012
DO - 10.1016/j.ajo.2018.09.012
M3 - Article
VL - 197
SP - 65
EP - 73
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
SN - 0002-9394
ER -