A randomized phase II study of Xilonix, a targeted therapy against interleukin 1α, for the prevention of superficial femoral artery restenosis after percutaneous revascularization

J Vasc Surg. 2016 Jan;63(1):133-41.e1. doi: 10.1016/j.jvs.2015.08.069. Epub 2015 Oct 1.

Abstract

Objective: The purpose of this study was to evaluate an anti-interleukin 1α antibody for its ability to reduce acute postprocedural inflammation, thereby reducing neointimal hyperplasia and restenosis after superficial femoral artery (SFA) angioplasty. Restenosis of the SFA after endovascular intervention is a common problem leading to 1-year primary patency as low as 40%. These failures are primarily due to the development of neointimal hyperplasia, resulting from arterial wall inflammation.

Methods: This was a randomized, phase II trial examining SFA restenosis in patients after percutaneous revascularization. Randomization occurred after successful revascularization, and patients were assigned to either the standard of care arm or the Xilonix (XBiotech USA, Inc, Austin, Tex) plus standard of care arm (N = 43). Xilonix was administered immediately after revascularization, every 2 weeks intravenously for four doses, and monthly subcutaneously until month 12. The major efficacy end points were target vessel event-free survival and incidence of major adverse cardiovascular events (MACEs).

Results: At 12 months of follow-up, MACE (43% vs 36%; P = .76) and target vessel restenosis (24% vs 27%; log-rank, P = .79) rates were not significantly different between the groups. At 3-month follow-up, which covers the intravenous dosing period, a trend toward lower incidence of restenosis (0 of 22 [0%] vs 2 of 21 [10%]; P = .14) and MACE (2 of 22 [9%] vs 5 of 21 [24%]; P = .22) was observed in the Xilonix cohort. Adverse events were equally distributed in both arms.

Conclusions: Xilonix was well tolerated. Observed tendency to improved vessel patency with intravenous dosing suggests Xilonix could potentially represent a safe and effective therapeutic approach to preserving vessel patency.

Trial registration: ClinicalTrials.gov NCT01270945.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angioplasty* / adverse effects
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / pharmacokinetics
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal, Humanized
  • Constriction, Pathologic
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Femoral Artery / drug effects*
  • Femoral Artery / pathology
  • Femoral Artery / physiopathology
  • Humans
  • Hyperplasia
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Neointima
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / physiopathology
  • Peripheral Arterial Disease / therapy*
  • Recurrence
  • Secondary Prevention / methods*
  • Time Factors
  • Treatment Outcome
  • United States
  • Vascular Patency / drug effects*

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • bermekimab

Associated data

  • ClinicalTrials.gov/NCT01270945