Phase I/IIa study examining the safety and tolerability of single and multiple rising intravitreal doses of BI 836880 in patients with wAMD

Abstract

Purpose : To assess the safety and tolerability of BI 836880, a dual vascular endothelial growth factor (VEGF)/angiopoietin-2 inhibitor, in a two-part single rising dose (SRD) and multiple rising dose (MRD) study in patients with wet age-related macular degeneration (wAMD).

Methods : This Phase I/IIa open-label, non-randomized study (NCT03861234) includes patients with wAMD who, in the SRD part and the first cohort of the MRD part (1.00 mg), have progressed despite ≥3 prior anti-VEGF injections. The second cohort of the MRD part (2.00 mg) will enroll treatment-naïve patients with wAMD. In the SRD part, patients received one single intravitreous injection of BI 836880 (either 0.06, 0.18, 0.50, 1.00, or 2.00 mg) and were followed for up to 43 days. Based on the highest tolerated doses identified in the SRD part, patients in the MRD part will receive three consecutive 1.00 or 2.00 mg doses of BI 836880 over a 3-month period. The primary endpoint is the number of patients with dose-limiting ocular events in the SRD part and the number of patients with drug-related adverse events (AEs) in the MRD part. Secondary endpoints in the MRD part include change from baseline in best-corrected visual acuity (BCVA) and central subfield foveal thickness.

Results : In the completed SRD part, 15 patients received BI 836880 (n=3 per dose group); all were white with a mean age of 76 years. In total, 40% of patients had an AE; all were ocular. No AEs were dose-limiting or drug-related; one patient had a serious AE of wAMD in the fellow eye. Overall, 26.7% of patients had procedure-related AEs (vitreous floaters, conjunctival hemorrhage, dry eye). The mean change in BCVA from baseline to end of study in the SRD part was +5.3, +7.3, +0.3, +6.0, and +7.0 letters (doses of 0.06, 0.18, 0.50, 1.00, and 2.00 mg, respectively). In the ongoing MRD part, four patients have been enrolled and received 1.00 mg BI 836880 to date; all are white with a mean age of 76.5 years. Two patients have had a reported AE, one of which was ocular. Neither was serious, dose-limiting, or drug-related.

Conclusions : BI 836880 was well tolerated by patients in the SRD part and has been well tolerated by patients in the MRD part to date, with no dose-limiting or drug-related AEs reported. BCVA data from the SRD part demonstrate preliminary signs of efficacy, which are being further investigated in the ongoing MRD part.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.