Table 1.
Study selection of six (6) research articles for review and meta-analysis outcomes for LCA2-RPE65 gene therapy.
|
Studies (n = 6)
(Journal) |
Trial Identifier (ClinicalTrials.gov) | Study Type/Viral Vector | Titre (vg (a))/Injection Vol. | Population (ITT (b)) | Age Range (in Years) | BCVA (c) (logMAR) | Ambulatory Navigation, Low Light Ambient Level (<4 lux) (RR (d)(e)) | FST (f) (Red Light), log10(cd.s/m2) | FST (f) (Blue Light), log10(cd.s/m2) | Retinal Thickness (OCT, µm) |
|---|---|---|---|---|---|---|---|---|---|---|
| Bainbridge et al., 2015 (NEJM) | NCT00643747 | Phase 1–2, open-label, non-randomized; rAAV 2/2. hRPE65p.hRPE65 | 1.0 × 1011 to 1.0 × 1012 vg; injection volume of 900 µL to 1 mL | 12 | 6–23 years (Median, 15y; Mean, 14.4y; CI 95%, 3.8) | Mean change BCVA of −0.008 logMAR (treated eyes) vs. −0.063 logMAR (untreated eyes), a difference of 0.06 logMAR (95% CI −0.14, 0.02) | Risk ratio of 5.00 (95% CI 0.27, 93.55) | Data unavailable | Data unavailable | Risk of ratio of 1.50 (95% CI 0.30, 7.43) |
| Jacobson et al., 2012 (Arch Ophthalmol) | NCT00481546 | Phase 1, open-label, non-randomized; rAAV2-RPE65 | 5.96 × 1010 to 17.88 × 1010 vg; injection volume of 150 µL to 450 µL | 15 | 11–30 years (Median, 20y; Mean, 19.6y; CI 95%, 3.1) | Mean change BCVA of −0.12 logMAR (treated eyes) vs. −0.05 logMAR (untreated eyes), a difference of −0.07 logMAR (95% CI −0.18, 0.04) | Risk ratio of 1.18 (95% CI 0.86, 1.61) | Mean change FST of 0.45 log10(cd.s/m2) (treated eyes) vs. −0.02 log10(cd.s/m2) (untreated eyes), a difference of 0.47 log10(cd.s/m2) (95% CI 0.24, 0.70) | Mean change FST of 1.59 log10(cd.s/m2) (treated eyes) vs. −0.05 log10(cd.s/m2) (untreated eyes), a difference of 1.64 log10(cd.s/m2) (95% CI 1.14, 2.14) | Risk of ratio of 1.00 (95% CI 0.31, 3.28) |
| Le Meur et al., 2018 (Mol Ther) | NCT01496040 | Phase 1/2, open, non-randomized; AAV2/4.-RPE65-RPE65 | 1.22 × 1010 to 4.8 × 1010 vg; injection volume of 200 µL to 800 µL | 9 | 9–42 years (Median, 22y; Mean, 24.1y; CI 95%, 7.8) | Mean change BCVA of −0.05 logMAR (treated eyes) vs. −0.02 logMAR (untreated eyes), a difference of −0.03 logMAR (95% CI −0.18, 0.12) | Data unavailable | Data unavailable | Data unavailable | Data unavailable |
| Russell et al., 2017 (Lancet) | NCT00999609 | Phase 3, open-labelled, randomised (RCT); AAV2-hRPE65v2 | 1.5 × 1011 vg; injection volume of 300 µL | 31 | 4–44 years (Median, 11y; Mean, 14.4y; CI 95%, 4.1) | Mean change BCVA of −0.163 logMAR (treated eyes) vs. −0.031 logMAR (untreated eyes), a difference of −0.13 logMAR (95% CI −0.29, 0.03) | Risk ratio of 3.6 (95% CI 1.04, 12.46) | Mean change FST of 1.29 log10(cd.s/m2) (treated eyes) vs. −0.16 log10(cd.s/m2) (untreated eyes), a difference of 1.45 log10(cd.s/m2) (95% CI 0.69, 2.21) | Mean change FST of 1.96 log10(cd.s/m2) (treated eyes) vs. −0.13 log10(cd.s/m2) (untreated eyes), a difference of 2.09 log10(cd.s/m2) (95% CI 0.61, 3.57) | Data unavailable |
| Testa et al., 2013 (Ophthalmology) | NCT00516477 | Phase 1, open-label, non-randomized (3-year study); AAV2-hRPE65v2 | 1.0 × 108 to 5.0 × 108 vg; injection volume of 150 µL to 300 µL | 5 | 11–26 years (Median, 19y; Mean, 19.8y; CI 95%, 7.9) | Mean change BCVA of −0.486 logMAR (treated eyes) vs. −0.264 logMAR (untreated eyes), a difference of −0.22 logMAR (95% CI −0.34, −0.10) | Risk ratio of 1.0 (95% CI 0.71, 1.41) | Data unavailable | Data unavailable | Data unavailable |
| Weleber et al., 2016 (Ophthalmology) | NCT00749957 | Phase 1–2, open-label, non-randomized; rAAV2-CB-hRPE65 | 1.0 × 108 to 5.0 × 108 vg | 12 | 6–39 years (Median, 31y; Mean, 24.8y; CI 95%, 8.5) | Mean change BCVA of −0.025 logMAR (treated eyes) vs. −0.046 logMAR (untreated eyes), a difference of 0.02 logMAR (95% CI −0.06, 0.11) | Data unavailable | Data unavailable | Data unavailable | Data unavailable |
| Summary meta-analyses | Phase 1, 1/2, 3; AAV2 | Range from 1.0 × 108 to 1.0 × 1012 vg; injection vol. 150 µL to 1 mL | Population n = 84 | Range 4–44 years | Summary weighted mean difference (MD) of −0.06 logMAR improvement over treated vs. untreated eye (95% CI −0.14, 0.02), p = 0.16 | RR improvement of 1.35, over treated vs. untreated eye (95% CI 0.78, 2.2.35), p = 0.29 | Summary weighted mean difference (MD) of FST (red) 0.89 log10(cd.s/m2) over treated vs. untreated eye (95% CI −0.06, 1.84), p = 0.07 | Summary weighted mean difference (MD) of FST (blue) 1.69 log10(cd.s/m2) over treated vs. untreated eye (95% CI 1.21, 2.16), p = 0.00001 | RR improvement of 1.15 (95% CI 0.45, 3.00), p = 0.77 | |
(a) vg—vector genomes; (b) ITT—intention to treat; (c) BCVA—Best corrected visual acuity, (logMAR); (d) RR—risk ratio; (e) 95% CI—95% confidence interval; (f) FST—full-field stimulus testing (red and blue wavelength), log10(cd.s/m2).