Session: 332. Anticoagulation and Antithrombotic Therapy: Novel Agents, Reversal Drugs and Indications
Hematology Disease Topics & Pathways:
Biological, antibodies, Therapies
Methods: In this phase 2, randomized, double-blind, placebo-controlled, single-administration study, AB023 (0.25 or 0.5 mg/kg) or placebo was injected into the HD circuit of 24 ESRD patients at the start of heparin-free HD (NCT03612856). All patients underwent three pre-dose HD procedures and four monitored post-dose HD sessions. In total, the study encompassed 168 individual HD sessions, 72 of which occurred pre-dose and 96 of which occurred post-dose. Safety parameters, including time to hemostasis at HD access site, prothrombin time, physical examinations, vital signs, electrocardiograms, clinical chemistry, immunogenicity and other adverse events (AEs), were recorded. Clotting within the hemodialyzer circuit was assessed using a visual clotting scale by investigators who were blinded to treatment. The frequency of circuit clot obstructions requiring dialyzer exchange was also recorded. Pharmacokinetic and pharmacodynamic parameters, including activated partial thromboplastin times, were also assessed. The study was approved by an ethics review board and all subjects provided written informed consent.
Results: AB023 demonstrated a favorable safety profile in ESRD patients. No drug-related AEs were noted. Clinically relevant bleeding did not occur in any patient, and the time to hemostasis at the HD access site was unchanged after AB023 administration. As expected, the aPTT was prolonged after AB023 administration, reaching saturation at both dose levels (about 2-fold prolongation) immediately after dosing, and remaining prolonged for up to 9 days with the high dose. Compared with pretreatment, the frequency of occlusive events requiring circuit exchange decreased by 68% and 50% in subjects given the 0.25 and 0.5 mg/kg AB023 respectively, while the number of occlusive events was numerically unchanged in the placebo arm. Likewise, the number of saline flushes required to maintain circuit patency decreased by 44% and 85%, and the incidence of high-grade clotting in the hemodialyzer as assessed by visual scoring decreased by 15% and 43% on day 1, 8% and 35% by day 3, and 0% and 19% by day 5 in the 0.25 and 0.5 mg/kg cohorts, respectively.
Conclusions: Anticoagulation with AB023 was well-tolerated and reduced clot formation within the HD circuit of ESRD patients. These findings suggest that inhibiting contact system activation could reduce medical device-initiated blood clot formation in patients.
Disclosures: Lorentz: Aronora, Inc.: Current Employment. Verbout: Aronora, Inc.: Current Employment. Shatzel: Aronora, Inc.: Consultancy. Wallisch: Aronora, Inc.: Current Employment. Markway: Aronora, Inc.: Current Employment. Tucker: Aronora, Inc.: Current Employment. Gruber: Aronora, Inc.: Current Employment, Current equity holder in private company.
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