Safety and tolerability of avacincaptad pegol in combination with ranibizumab in treatment-naïve patients with neovascular age-related macular degeneration: results from a phase 1 and phase 2a study.

OBJECTIVE

To assess the safety and tolerability of avacincaptad pegol (ACP), a Food and Drug Administration-approved therapy for geographic atrophy, administered in combination with ranibizumab, an approved therapy for neovascular age-related macular degeneration (nAMD), in patients with nAMD.

METHODS

The phase 1 study (NCT00709527) was a two-part, ascending-dose and parallel-group, open-label trial that assessed the safety, tolerability and pharmacokinetic profile of monthly intravitreal injections of ACP (0.03, 0.3, 1, 2, 3 mg) in combination with ranibizumab (0.5 mg) on the same day in treatment-naïve patients with nAMD (n=43 patients received a maximum of 6 injections). The phase 2a study (NCT03362190) was an open-label trial assessing the 6-month safety of intravitreal injections of ACP administered in combination with ranibizumab in treatment-naïve patients with nAMD (n=64). Patients received either ACP 2 mg or 4 mg either 14 days or 1 month apart, given on the same day or 2 days after ranibizumab. Primary outcome measures were safety and tolerability.

RESULTS

During the phase 1 study, there were no dose-limiting toxicities at any dose level. In both studies, ocular treatment-emergent adverse events were mostly mild or moderate, with the most reported events related to the injection procedure. There were no clinically significant increases in intraocular pressure or cumulative increases with multiple injections over time. There were no safety issues identified through measurement of visual acuity.

CONCLUSIONS

Coadministration of ACP and ranibizumab in treatment-naïve patients with nAMD was well tolerated across different dosing regimens with no new safety issues based on results from two independent studies.