title: A randomized, partially blinded, multicenter, active-controlled, dose-ranging study assessing the safety, efficacy, and pharmacodynamics of the REG1 anticoagulation system in patients with acute coronary syndromes: design and rationale of the RADAR Phase IIb trial.
abstract: Anticoagulants are the cornerstone of current acute coronary syndrome (ACS) therapy; however, anticoagulation regimens that aggressively reduce ischemic events are almost uniformly associated with more bleeding. REG1, an anticoagulation system, consists of RB006 (pegnivacogin), an RNA oligonucleotide factor IXa inhibitor, and RB007 (anivamersen), its complementary controlling agent. Phase I and IIa studies defined predictable relationships between doses of RB006, RB007, and degree of antifactor IX activity. The efficacy and safety of REG1 for the treatment of patients with ACS managed invasively and the safety of reversing RB006 with RB007 after cardiac catheterization are unknown. Randomized, partially-blinded, multicenter, active-controlled, dose-ranging study assessing the safety, efficacy, and pharmacodynamics of the REG1 anticoagulation system compared to unfractionated heparin or low molecular heparin in subjects with acute coronary syndrome (RADAR) is designed to assess both the efficacy of the anticoagulant RB006 and the safety of a range of levels of RB006 reversal with RB007. The objectives of RADAR are (1) to determine the safety of a range of levels of RB006 reversal with RB007 after catheterization, (2) to confirm whether a dose of 1 mg/kg RB006 results in near-complete inhibition of factor IXa in patients with ACS, and (3) to assess the efficacy of RB006 as an anticoagulant in patients with ACS undergoing percutaneous coronary intervention.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. povsi001@mc.duke.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Povsic
authors.forename: Mauricio G
authors.initials: MG
authors.lastname: Cohen
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Buller
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Jan H
authors.initials: JH
authors.lastname: Cornel
authors.forename: Jarosław D
authors.initials: JD
authors.lastname: Kasprzak
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Diane
authors.initials: D
authors.lastname: Joseph
authors.forename: William A
authors.initials: WA
authors.lastname: Wargin
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Rusconi
authors.forename: Steven L
authors.initials: SL
authors.lastname: Zelenkofske
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D052157:Aptamers, Nucleotide / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods; D006801:Humans; D015337:Multicenter Studies as Topic; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016032:Randomized Controlled Trials as Topic / Q000379:methods
chemical_list: D052157:Aptamers, Nucleotide; D009841:Oligonucleotides; C515724:RB 006; C515725:RB 007