Abstract
Purpose :
APX3330 is a novel, small molecule inhibitor of Ref-1, a transcriptional regulator of key angiogenic (VEGF) and inflammatory signaling pathways relevant to diabetic retinopathy (DR), diabetic macular edema (DME), and neovascular age-related macular degeneration (AMD). In over 300 subjects in 11 prior Phase 1 and Phase 2 clinical trials, oral APX3330 demonstrated a favorable safety and tolerability profile with doses up to 600mg over multiple months in healthy subjects, hepatitis patients, and solid tumor patients. The most common related adverse events (AEs) were mild diarrhea or soft stool (4% with APX3330, 2% with placebo) and mild rash or pruritis (4% with APX3330, 1% with placebo). This abstract reports the masked safety and tolerability of APX3330 in the ongoing 24-week ZETA-1 Phase 2 clinical trial.
Methods :
The ZETA-1 trial is a randomized, placebo-controlled, double-masked, multi-center study designed to evaluate the efficacy and safety of oral APX3330 600mg daily dose over 24 weeks in DR patients. Safety data for 35 masked subjects who have been randomized to APX3330 or placebo has been evaluated and summarized, which represents over 1,500 total subject exposure days.
Results :
In both trial arms, there have been 28 AEs reported in 16 (46%) of subjects. No adverse events have been thought to be related to the oral study medication, aside from two episodes of diarrhea in the same subject. Five serious AEs have been reported, all designated unrelated to study medication (2 cellulitis, 1 abnormal involuntary movement; before dosing 1 CAD and 1 osteomyelitis). Only 2 subjects have withdrawn from the trial due to non-serious AEs (vasovagal near syncope and worsening diabetic macular edema). With oral administration, no significant organ toxicity (liver, heart, kidney, brain, lung), no vital sign abnormalities (blood pressure and heart rate), and no rash were observed.
Conclusions :
Similar to prior trials in healthy subjects, cancer patients, and hepatitis patients, oral administration of APX3330 and placebo have demonstrated a favorable ophthalmic and systemic safety and tolerability profile. Addition safety data from the ongoing ZETA-1 trial will be evaluated to further characterize the efficacy and safety of APX3330 for the oral treatment of diabetic eye diseases.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.