Intravitreal Combined Aflibercept + Anti-Platelet-Derived Growth Factor Receptor ß for Neovascular Age-Related Macular Degeneration: Results of the Phase 2 CAPELLA Trial.

ABSTRACT

PURPOSE: To compare the efficacy and safety of intravitreal aflibercept + anti-platelet-derived growth factor receptor ß (PDGFRß) combination with intravitreal aflibercept injection (IAI) monotherapy in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). DESIGN: Phase 2, randomized, double-masked study. PARTICIPANTS: A total of 505 patients (eyes) with nAMD. METHODS: Patients were randomized 122 to low-dose combination intravitreal anti-PDGFRß 1 mg and aflibercept 2 mg (LD combo), high-dose combination intravitreal anti-PDGFRß 3 mg and aflibercept 2 mg (HD combo), or IAI alone every 4 weeks through week 12. At week 12, patients in the HD combo and IAI groups were re-randomized to continue as assigned or switch to HD combo → IAI or IAI → HD combo and dosed every 4 weeks through week 28. During weeks 28 to 52, patients received treatment as needed per prespecified criteria. This report presents efficacy through week 28 and safety through week 52. MAIN OUTCOME MEASURES: Mean best-corrected visual acuity (BCVA) change from baseline at week 12 (primary end point). RESULTS: At week 12, mean BCVA gains from baseline were 5.8, 5.8, and 7.5 letters with LD combo, HD combo, and IAI, respectively (P = 0.21 for LD combo and P = 0.10 for HD combo vs. IAI). The corresponding proportions of eyes that gained ≥15 letters were 12%, 19%, and 22%, respectively. Mean reductions in central retinal thickness from baseline were 126.1, 127.1, and 126.9 µm, respectively. Proportions of eyes with complete resolution of fluid from baseline were 35%, 24%, and 42%, respectively. Vision and anatomic outcomes at week 28 were consistent with the week 12 results. Through week 52, the incidence of intraocular inflammation was 1.0%, 7.5%, 2.1%, 2.1%, and 0%, respectively. The incidence of Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events was 1.9%, 0.9%, 1.1%, 2.1%, and 1.9%, respectively. CONCLUSIONS: Intravitreal aflibercept + anti-PDGFRß did not improve BCVA over IAI alone. Anatomic outcomes evaluating complete fluid resolution favored IAI. Adverse events were consistent with the reported IAI safety profile, except for a higher frequency of intraocular inflammation in the HD combo group.