First-in-Human Study to Evaluate the Safety and Early Efficacy of a Novel Drug and Delivery System for Stabilizing Small to Medium-Sized Infrarenal Abdominal Aortic Aneurysms

Abstract

To establish that a one-time, local administration of a novel drug, 1,2,3,4,6-pentagalloyl glucose (PGG) to the abdominal aortic aneurysm (AAA) wall is safe and potentially effective in stabilizing or slowing the growth of small to medium-sized AAA in humans in a multicenter study with ≤3 years of follow-up. Patients with AAA of <5.5 cm diameter were recruited. Via transfemoral access, 25 mL of PGG solution were delivered to the aneurysm wall with a weeping balloon over 3 minutes after infrarenal occlusion. Patients were assessed with computed tomography angiography at 1, 6, 12, 24, and 36 months. Core laboratory values of aneurysm sac maximum diameter and sac volume measurements were used to determine growth. Primary endpoints were technical success and safety (major adverse events at 30 days). Secondary endpoint was growth stabilization defined as freedom from aneurysm sac enlargement (diameter >5 mm/year, or volume increase of >10% per year). Twenty-one patients (20 male), mean age 69, were treated at five centers from June 2019 to August 2022. Technical success was 100%. Four patients showed transient elevation of liver enzyme levels, which returned to normal by 30 days with no clinical symptoms. Follow-up computed tomography angiography data showed average AAA diameter change of 0.2 mm (n = 18), 1.1 mm (n = 7), 2.0 mm (n = 5), and 0.8 mm (n = 2) from baseline at 6, 12, 24, and 36 months. Average volume changes were 2.5%, 9.6%, 24.3%, and 11.6% respectively. At 12 months, none of the aneurysms showed growth >5.0 mm and three had volume growth >10%. Local delivery of PGG in small to medium-sized aneurysms is safe and early efficacy data are promising. The potential for PGG to stabilize or slow growth of small to medium-sized AAA merits further evaluation in a randomized, controlled clinical trial.