Publication Date
2-1-2024
Journal
Nature Medicine
DOI
10.1038/s41591-023-02794-7
PMID
38365952
PMCID
PMC10878964
PubMedCentral® Posted Date
2-16-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Male, Female, Blood Coagulation, Anticoagulants, Hemorrhage, Renal Insufficiency, Renal Dialysis, Double-Blind Method, Antibodies, Monoclonal, Humanized, Drug development, End-stage renal disease
Abstract
Individuals with kidney failure undergoing hemodialysis are at elevated risk for thromboembolic events. Factor (F) XI, which is in the intrinsic pathway of coagulation, is emerging as an attractive target for new anticoagulants that may be safer than existing agents. Osocimab-an inhibitory FXIa antibody-is a potential treatment option for such patients. We conducted a phase 2b, double-blind, placebo-controlled trial, in which 704 participants (448 male, 256 female) with kidney failure undergoing hemodialysis were randomized to receive lower- or higher-dose osocimab or placebo. In total, 686 participants (436 male, 250 female) received treatment for ≤18 months (planned minimal treatment period of 6 months). The co-primary outcomes were clinically relevant bleeding (a composite of major and clinically relevant nonmajor bleeding) and a composite of the incidence of moderate, severe or serious adverse events. Clinically relevant bleeding occurred in 16/232 (6.9%) and 11/224 (4.9%) participants who received lower- and higher-dose osocimab, respectively, and in 18/230 participants (7.8%) who received a placebo. For the composite adverse event endpoint, incidences were 51%, 47% and 43% in the lower-dose osocimab, higher-dose osocimab and placebo groups, respectively. These results suggest that osocimab is associated with a low risk of bleeding and is generally well tolerated in this population; findings that require confirmation in larger trials.
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Diseases Commons, Medical Sciences Commons, Medical Specialties Commons
Comments
ClinicalTrials.gov identifier, NCT04523220.
Associated Data