Phase 1b Randomized Study of Antidote-Controlled Modulation of Factor IXa Activity in Patients With Stable Coronary Artery Disease

Whether selective factor IXa inhibition produces an appropriate anticoagulant effect when combined with platelet-directed therapy in patients with stable coronary artery disease is unknown. REG1 consists of RB006 (drug), an injectable RNA aptamer that specifically binds and inhibits factor IXa, and RB007 (antidote), the complementary oligonucleotide that neutralizes its anti-IXa activity. We evaluated the safety, tolerability, and pharmacodynamic profile of REG1 in a randomized, double-blind, placebo-controlled study, assigning 50 subjects with coronary artery disease taking aspirin and/or clopidogrel to 4 dose levels of RB006 (15, 30, 50, and 75 mg) and RB007 (30, 60, 100, and 150 mg). The median age was 61 years (25th and 75th percentiles, 56 and 68 years), and 80% of patients were male. RB006 increased the activated partial thromboplastin time dose dependently; the median activated partial thromboplastin time at 10 minutes after a single intravenous bolus of 15, 30, 50, and 75 mg RB006 was 29.2 seconds (25th and 75th percentiles, 28.1 and 29.8 seconds), 34.6 seconds (25th and 75th percentiles, 30.9 and 40.0 seconds), 46.9 seconds (25th and 75th percentiles, 40.3 and 51.1 seconds), and 52.2 seconds (25th and 75th percentiles, 46.3 and 58.6) (P