First human experience with local delivery of novel antisense AVI-4126 with Infiltrator catheter in de novo native and restenotic coronary arteries: 6-month clinical and angiographic follow-up from AVAIL study.

Background: A novel antisense phosphorodiamidate morpholino oligomer, AVI-4126, was shown to be effective in reducing neointimal formation in different animal models following delivery by pluronic gels, porous balloon catheters, and coated stents. The purpose of the AVAIL study was to investigate both the safety and the efficacy of AVI-4126 delivered locally via Infiltrator catheter after percutaneous coronary intervention in humans.

Methods: The AVAIL trial is a prospective, evaluator-blinded, randomized study including clinical follow-up at 30 days and 6 months after intervention and 6-month angiographic and intravascular ultrasound (IVUS) follow-up. An Infiltrator catheter was advanced to target lesion and either drug was delivered (Groups A and B) or catheter was advanced (Group C) after stent implantation in de novo lesions or percutaneous transluminal coronary angioplasty in restenotic lesions. Primary end points include major adverse cardiovascular events (MACE), target vessel revascularization (TVR), angiographic restenosis, and IVUS at 6 months.

Results: Forty-four patients with either de novo lesions or restenosis were randomized into three groups: (A) low dose, 3 mg (19 patients); (B) high dose, 10 mg (15 patients), and (C) control (10 patients). Baseline angiographic characteristics did not differ between the groups (reference vessel diameter, 2.5-4 mm; lesion length, <16 mm). Procedural success was 81. 82% (unable to advance Infiltrator catheter to target lesion in 8 patients, 5 from Group B and 3 from Group C). There was no in-hospital or 30-day MACE recorded in any group. Clinical follow-up was available in 25 patients. At 6 months, four patients (50%) from the control group (Group C, n=8) and 7 (100%) patients from the low-dose group (Group A, n=7) required TVR. In contrast, in the high-dose group (Group B, n=10) only 1 patient (10%) needed TVR. Angiographic follow-up in 25 patients (Group A, 8 patients; Group B, 7 patients; and Group C, 10 patients) demonstrated late loss of 1.4+ to 0.54, 0.8+ to 0.55, and 1.5+ to 0.65, respectively (P=.025). Binary restenosis was 38% in Group C (control), 29% in Group A (low dose), and 0% in Group B (high dose).

Conclusion: Local delivery of antisense is feasible. These preliminary findings from the small cohort of patients require confirmation in a larger trial utilizing more sophisticated drug-eluting technologies.