A phase 1 ascending dose study of a subcutaneously administered factor IXa inhibitor and its active control agent.

Journal Article


The REG2 anticoagulation system consists of pegnivacogin, a subcutaneously administered aptamer factor IXa inhibitor, and its intravenous control agent, anivamersen.


To assess the safety, tolerability and pharmacokinetic and pharmacodynamic responses of REG2.


In this phase 1a study, 36 healthy volunteers were enrolled into five cohorts and given one dose of pegnivacogin. Cohorts 1 (n = 6) and 1A (n = 4) received 0.5 mg kg(-1); cohort 2 (n = 6) received 1.0 mg kg(-1); cohort 3 (n = 6) received 3.0 mg kg(-1); and cohort 4 (n = 8) received 2.0 mg kg(-1) . In cohorts 1-3, two subjects were randomized to placebo. Cohort 4 subjects were subsequently randomized to single-dose (n = 4) or multidose (n = 4) anivamersen.


The mean maximum observed concentrations of pegnivacogin in cohorts 1, 1A, 2 and 3 at median time were 5.16 μg mL(-1) at 84 h, 5.19 μg mL(-1) at 72 h, 9.32 μg mL(-1) at 90 h, and 32.5 μg mL(-1) at 84 h, respectively. The maximum relative activated partial thromboplastin time and time needed to achieve this were 1.18 at 2 days, 1.16 at 2 days, 1.27 at 3 days, and 1.85 at 2 days, respectively. The calculated mean half-life and mean residence times of pegnivacogin were 6.12 days and 9.6 days, respectively. There was rapid reversal with intravenous anivamersen, although subsequent reaccumulation of pegnivacogin was observed.


In our first-in-human study, REG2 was well tolerated and provided dose-proportional anticoagulation for several days after a single subcutaneous dose, with complete, although transient, reversal by its control agent. This study demonstrates the first application of a subcutaneously administered aptamer, and represents a potential advance in aptamer therapeutics.

Full Text

Duke Authors

Cited Authors

  • Vavalle, JP; Rusconi, CP; Zelenkofske, S; Wargin, WA; Alexander, JH; Becker, RC

Published Date

  • July 2012

Published In

Volume / Issue

  • 10 / 7

Start / End Page

  • 1303 - 1311

PubMed ID

  • 22500821

Pubmed Central ID

  • 22500821

Electronic International Standard Serial Number (EISSN)

  • 1538-7836

International Standard Serial Number (ISSN)

  • 1538-7933

Digital Object Identifier (DOI)

  • 10.1111/j.1538-7836.2012.04742.x


  • eng