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Brian B Berger, Susan E Yanni, Andreas Wenzel, Andreas Weichselberger, Jean Pierre Hubschman; Efficacy of RTH258 (ESBA1008), an Anti-VEGF Agent, Applied by Microvolume Injection or Infusion in Subjects with Neovascular AMD. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):821.
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RTH258, a humanized single-chain antibody fragment directed against VEGF-A, is being developed for the treatment of nAMD. RTH258 has optimized solubility and can be highly concentrated, allowing reduced injection volumes for intravitreal application. Here, we report data on the efficacy of RTH258 microvolume (10µL) application, via intravitreal injection or intravitreal infusion, in subjects with nAMD.
Prospective, randomized, multi-center, controlled, assessor-masked, parallel-group study. Subjects had untreated, active CNV due to AMD. Within each of two cohorts (injection and infusion), subjects were randomized 10:3 to receive RTH258 or ranibizumab (RBZ). RBZ was included for masking purposes only. In the injection cohort, subjects received a single microvolume intravitreal injection of RTH258 at d0. In the infusion cohort, subjects received a microvolume intravitreal infusion over 16 minutes. All subjects had visits on days 0, 7, 14, 28 and 42. The primary efficacy endpoint was the percentage of responders, defined as those meeting at least 3 of 4 criteria: 1) ≥ 4 letter gain in BCVA at d14; 2) ≥ 4 letter gain in BCVA at d28; 3) ≥ 80 µm decrease in CSFT at d14; 4) ≥ 80 µm decrease in CSFT at d28. Ten RTH258 subjects per cohort were sufficient to identify a 60% responder rate at a 1-sided alpha level of 0.05 with a power of 94%. A responder rate of 15% represents no relevant treatment effect (null hypothesis).
26 subjects,13 in each cohort, were randomized. RTH258 produced responder rates of 70% (7/10; 90% confidence interval, 39-91%) when injected and 60% (6/10; 90% CI, 30-85%) when infused, exceeding the 15% responder rate (p ≤ 0.0014).
Microvolumes of RTH258, delivered intravitreally by injection or infusion, are efficacious in improving BCVA and CSFT in the majority of subjects. A microvolume delivery of RTH258 may permit sustained delivery and/or simultaneous treatment with multiple drugs, while maintaining the standard injection volume of 50µl.
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