NEJM evidence · 2025
Cell-Based Ciliary Neurotrophic Factor Therapy for Macular Telangiectasia Type 2.
СтатьяРандомизированное исследованиеКлиническое исследование III фазыМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Chew Emily Y, Gillies Mark, Jaffe Glenn J, Gaudric Alain, Egan Cathy, Constable Ian, Clemons Traci, Aaberg Thomas, Manning Debora C, Hohman Thomas C, Bird Alan, Friedlander Martin, MacTel CNTF NTMT-03 Research investigators
Аннотация
BACKGROUND: Revakinagene taroretcel (NT-501) is an encapsulated cell therapy producing ciliary neurotrophic factor that slowed retinal degeneration in patients with macular telangiectasia type 2 (MacTel) in phase 2 trials.
METHODS: In NTMT-03-A and NTMT-03-B - identically designed phase 3, multicenter, randomized sham-controlled trials - we evaluated efficacy and safety of NT-501 in MacTel. The primary end point was rate of change in ellipsoid zone area (EZA) (photoreceptor) loss over 24 months (mm2/24 months). Secondary outcomes included changes in retinal sensitivity, reading speed, and National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) scores (range, 0 to 100; higher scores indicate better function). Safety end points included the proportion of participants experiencing one or more treatment-emergent serious adverse event(s) and loss of 15 or more letters in best-corrected visual acuity (BCVA). Delayed dark adaptation and miosis were among the monitored adverse events.
RESULTS: In NTMT-03-A, adjusted rates of change of EZA loss were 0.075 mm2/24 months (95% confidence interval [CI], 0.051 to 0.099) and 0.166 mm2/24 months (95% CI, 0.141 to 0.191) in the NT-501 (n=58) and sham (n=57) groups, respectively, with a difference of -0.091 mm2/24 months (95% CI, -0.125 to -0.056; P<0.001) between groups. In NTMT-03-B, rates of EZA loss were 0.111 mm2/24 months (95% CI, 0.084 to 0.139) and 0.160 mm2/24 months (95% CI, 0.131 to 0.189) in the NT-501 (n=59) and sham (n=54) groups, respectively, with a difference of -0.049 mm2/24 months (95% CI, -0.089 to -0.008; P=0.02). Retinal sensitivity and reading-speed changes between groups were inconsistent in the trials. NEI VFQ-25 scores, BCVA loss, and treatment-emergent serious adverse events did not differ between treatment groups. Miosis was experienced by 17% and 14% of participants receiving NT-501 in NTMT-03-A and NTMT-03-B, respectively, and by none of the participants in sham groups. Delayed dark adaptation was experienced by 17% and 24% of participants receiving NT-501 in NTMT-03-A and NTMT-03-B, respectively, by none in the NTMT-03-A sham group, and by 2% in the NTMT-03-B sham group.
CONCLUSIONS: NT-501 for MacTel resulted in statistically significantly reduced EZA loss compared with sham procedures. (Funded by Neurotech Pharmaceuticals; ClinicalTrials.gov numbers, NCT03316300 and NCT03319849.).
METHODS: In NTMT-03-A and NTMT-03-B - identically designed phase 3, multicenter, randomized sham-controlled trials - we evaluated efficacy and safety of NT-501 in MacTel. The primary end point was rate of change in ellipsoid zone area (EZA) (photoreceptor) loss over 24 months (mm2/24 months). Secondary outcomes included changes in retinal sensitivity, reading speed, and National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) scores (range, 0 to 100; higher scores indicate better function). Safety end points included the proportion of participants experiencing one or more treatment-emergent serious adverse event(s) and loss of 15 or more letters in best-corrected visual acuity (BCVA). Delayed dark adaptation and miosis were among the monitored adverse events.
RESULTS: In NTMT-03-A, adjusted rates of change of EZA loss were 0.075 mm2/24 months (95% confidence interval [CI], 0.051 to 0.099) and 0.166 mm2/24 months (95% CI, 0.141 to 0.191) in the NT-501 (n=58) and sham (n=57) groups, respectively, with a difference of -0.091 mm2/24 months (95% CI, -0.125 to -0.056; P<0.001) between groups. In NTMT-03-B, rates of EZA loss were 0.111 mm2/24 months (95% CI, 0.084 to 0.139) and 0.160 mm2/24 months (95% CI, 0.131 to 0.189) in the NT-501 (n=59) and sham (n=54) groups, respectively, with a difference of -0.049 mm2/24 months (95% CI, -0.089 to -0.008; P=0.02). Retinal sensitivity and reading-speed changes between groups were inconsistent in the trials. NEI VFQ-25 scores, BCVA loss, and treatment-emergent serious adverse events did not differ between treatment groups. Miosis was experienced by 17% and 14% of participants receiving NT-501 in NTMT-03-A and NTMT-03-B, respectively, and by none of the participants in sham groups. Delayed dark adaptation was experienced by 17% and 24% of participants receiving NT-501 in NTMT-03-A and NTMT-03-B, respectively, by none in the NTMT-03-A sham group, and by 2% in the NTMT-03-B sham group.
CONCLUSIONS: NT-501 for MacTel resulted in statistically significantly reduced EZA loss compared with sham procedures. (Funded by Neurotech Pharmaceuticals; ClinicalTrials.gov numbers, NCT03316300 and NCT03319849.).