Abstract
Purpose :
Preclinical data suggest that an 8 mg intravitreal aflibercept injection (IAI) may intensify and prolong the therapeutic effect of IAI 2 mg. CANDELA, a phase 2, randomized, single-masked, open-label, 44-week clinical trial (NCT04126317) assessed the safety and efficacy of IAI 8 mg versus IAI 2 mg in patients with neovascular age-related macular degeneration (nAMD).
Methods :
Treatment-naïve patients (≥50 years old) with active subfoveal choroidal neovascularization secondary to nAMD and a best corrected visual acuity (BCVA) of 78 to 24 letters (approximately 20/32 to 20/320) in the study eye were enrolled. A total of 106 patients were randomized 1:1 to receive 3 monthly doses of either IAI 2 mg (n=53) or IAI 8 mg (n=53) followed by doses at Week 20 and 32. The primary end points were safety and the proportion of eyes without retinal fluid in the center subfield at Week 16.
Results :
Overall, majority of the patients were female (62.3%); the mean (SD) age was 77.4 (8.0) years and mean (SD) baseline BCVA was 58.0 (12.1) letters. The incidence of ocular-related adverse events (AEs) through Week 16 was 17.0% (9/53) for the IAI 8 mg group and 22.6% (12/53) for the IAI 2 mg group. No new safety signals were identified; no AEs of intraocular inflammation, occlusive vasculitis, or anti-platelet trialists' collaboration (APTC)-defined arterial thromboembolic events were reported through Week 16. The proportion of eyes with no retinal fluid in the center subfield at Week 16 was 50.9% (27/53) for the IAI 8 mg group and 34.0% (18/53) for IAI 2 mg group (treatment difference, 17.0% [95% CI, −1.6%, 35.5%]; P=0.0770). Compared to the IAI 2 mg group, eyes in the IAI 8 mg group showed a numerically greater reduction from baseline in median central subfield thickness (−161 µm vs −96 µm), and a numerically higher increase from baseline in mean BCVA (8.4 vs 6.5 letters) at Week 16.
Conclusions :
The overall safety of IAI 8 mg was similar to that of IAI 2 mg at Week 16. The observed anatomic and functional improvements with IAI 8 mg suggest potential additional therapeutic benefit over IAI 2 mg in patients with nAMD. The data support further development of IAI 8 mg.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.