Abstract Number: PB0302
Meeting: ISTH 2020 Congress
Background: Ciraparantag is in clinical development as a reversal agent for various anticoagulants including non-vitamin K oral anticoagulants (NOACs). Ciraparantag was previously shown to reverse the anticoagulant effects of edoxaban and enoxaparin, as measured by whole blood clotting time (WBCT).
Aims: Two Phase 2 studies evaluated the efficacy (measured by WBCT) and safety of ciraparantag for reversal of anticoagulation induced by apixaban or rivaroxaban in healthy adults.
Methods: Two randomized, placebo-controlled, dose-ranging studies were conducted in healthy subjects age 50-75 years. Study 1 subjects received apixaban 10 mg orally twice daily for 3.5 days. Study 2 subjects received rivaroxaban 20 mg orally once daily for 3 days. In both studies, subjects at steady-state anticoagulation were randomized 3:1 to a single IV dose of ciraparantag (Study 1: 30, 60, or 120 mg; Study 2: 30, 60, 120 or 180 mg) or placebo. Efficacy was based on WBCT at multiple timepoints over 24 hours. Subjects and technicians performing WBCT testing were blinded to treatment.
Results: Across both studies, preliminary data are available for 80 subjects (60 ciraparantag, 20 placebo). Among subjects anticoagulated to ≥120% of baseline WBCT, reversal of WBCT to ≤110% of baseline within 1 hour post-dose and sustained through 5 hours was observed in Study 1 (apixaban) in 83%, 100%, and 0% of subjects receiving ciraparantag 60mg, 120mg, or placebo, respectively; and in Study 2 (rivaroxaban) in 92%, 92%, 100%, and 0% of subjects receiving ciraparantag 60mg, 120mg, 180mg, or placebo, respectively. The most common adverse events related to ciraparantag were mild, transient sensations of warmth (reported as hot flashes or flushing). Final results from all dose cohorts will be presented.
Conclusions: Ciraparantag single IV doses ≥60 mg showed rapid and sustained reversal of anticoagulation in high proportions of subjects anticoagulated with apixaban or rivaroxaban, and was well tolerated.
To cite this abstract in AMA style:Ansell J, Bakhru S, Villano S, Luo X. Efficacy and Safety of Ciraparantag in Reversing Apixaban and Rivaroxaban as Measured by Whole Blood Clotting Time in Healthy Adults [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/efficacy-and-safety-of-ciraparantag-in-reversing-apixaban-and-rivaroxaban-as-measured-by-whole-blood-clotting-time-in-healthy-adults/. Accessed August 5, 2020.
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