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- Title
Effect of High-Dose Intravitreal Aflibercept, 8 mg, in Patients With Neovascular Age-Related Macular Degeneration: The Phase 2 CANDELA Randomized Clinical Trial.
- Authors
Wykoff, Charles C.; Brown, David M.; Reed, Kimberly; Berliner, Alyson J.; Gerstenblith, Adam T.; Breazna, Aurora; Abraham, Prema; Fein, Jordana G.; Chu, Karen W.; Clark, W. Lloyd; Leal, Sergio; Schmelter, Thomas; Hirshberg, Boaz; Yancopoulos, George D.; Vitti, Robert
- Abstract
This randomized clinical trial assesses the safety and efficacy of aflibercept, 8 mg, in patients with neovascular age-related macular degeneration. Key Points: Question: How do the efficacy and safety of intravitreal aflibercept, 8 mg, in patients with neovascular age-related macular degeneration (nAMD) compare with aflibercept, 2 mg? Findings: In this phase 2 randomized trial of 106 patients, more eyes treated with 8-mg vs 2-mg aflibercept had no fluid in the central subfield at week 16, although the difference was not statistically significant. Safety profiles were similar for both doses. Meaning: Consistent but not statistically significant anatomic and visual gains favoring 8 mg over 2 mg of aflibercept coupled with no new safety signals suggest potential therapeutic benefit, which is being investigated in pivotal trials. Importance: Aflibercept, 8 mg, may have greater therapeutic benefits compared with aflibercept, 2 mg, in patients with neovascular age-related macular degeneration (nAMD), including potentially improved outcomes and decreased treatment burden. Objective: To assess safety and efficacy of aflibercept, 8 mg, in patients with nAMD. Design, Setting, and Participants: The CANDELA trial was a phase 2, randomized, single-masked, open-label, 44-week clinical trial conducted in the US. Treatment-naive patients with active subfoveal choroidal neovascularization secondary to nAMD and a best-corrected visual acuity score of 78 to 24 letters (approximately 20/32 to 20/320) in the study eye were enrolled between November 2019 and November 2021. Interventions: Eligible participants were randomized 1:1 to receive 3 monthly doses of 8 mg (70 μL) or 2 mg (50 μL) of aflibercept followed by doses at weeks 20 and 32. Main Outcomes and Measures: Coprimary end points were the proportion of eyes without fluid (absence of intraretinal and subretinal fluid) in the central subfield at week 16 and safety. Results: All 106 eligible eyes were randomized to receive aflibercept, 8 mg (n = 53), or aflibercept, 2 mg (n = 53). Overall, 66 participants (62.3%) were female. The proportion of eyes without fluid in the central subfield with 8-mg vs 2-mg aflibercept was 50.9% (n = 27) vs 34.0% (n = 18) (difference, 17.0 [95% CI, –1.6 to 35.5] percentage points; P =.08) at week 16 and 39.6% (n = 21) vs 28.3% (n = 15) (difference, 11.3 [95% CI, –6.6 to 29.2] percentage points; nominal P =.22) at week 44. At week 44, mean (SE) change in central retinal thickness was –159.4 (16.4) vs –137.2 (22.8) μm with 8 mg vs 2 mg of aflibercept, respectively (least squares mean difference, –9.5 [95% CI, –51.4 to 32.4]; nominal P =.65) and mean (SE) change in best-corrected visual acuity score was +7.9 (1.5) vs +5.1 (1.5) letters (least squares mean difference, +2.8 [95% CI, –1.4 to +7.0]; nominal P =.20). No differences in safety profiles between the groups were observed. Conclusions and Relevance: Although aflibercept, 8 mg, did not achieve the primary efficacy end point at week 16 at the 2-sided significance level of 5%, the observed trends in anatomic and visual improvements over 44 weeks with aflibercept, 8 mg, indicate potential additional therapeutic benefit over aflibercept, 2 mg. No new safety signals were observed over 44 weeks. These findings support further evaluation of aflibercept, 8 mg, in pivotal trials of exudative retinal diseases including nAMD and diabetic macular edema. Trial Registration: ClinicalTrials.gov Identifier: NCT04126317
- Publication
JAMA Ophthalmology, 2023, Vol 141, Issue 9, p834
- ISSN
2168-6165
- Publication type
Article
- DOI
10.1001/jamaophthalmol.2023.2421