Category: Clinical Obstetrics
Poster Session IV
Severe postpartum hemorrhage (PPH) unresponsive to first- and second-line therapies is treated with massive transfusion and aggressive procedures to compensate for and control blood loss. Recombinant factor VIIa (rFVIIa) has demonstrated some efficacy in this scenario, but has limited use due to thromboembolic risks. To address this liability, CT-001, a novel next generation rFVIIa, was developed to increase safety and improve activity. CT-001 has 4 N-glycans with terminal sialic acid residues removed to promote active clearance via the asialoglycoprotein receptor for lower thrombogenicity risk, and P10Q/K32E substitutions introduced to its gamma-carboxyglutamic (Gla)-domain for enhanced activity (Fig 1). While previous in vitro and in vivo studies support the success of these efforts (Sim DS et al, Thromb Res 2022 215:58), we sought to assess the ex-vivo hemostatic activity of CT-001 in peripartum blood samples.
Study Design:
Pregnant women (n=5) from 2 study sites were enrolled in this prospective observational study. Women at higher risk of PPH were preferentially enrolled. Baseline blood samples were collected up to 3 days before delivery. Samples were obtained again 45 (+/-15) mins after delivery. The dose-response of plasma samples to CT-001 and rFVIIa were evaluated by activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin generation assay (TGA).
Results:
In all assays, CT-001 and rFVIIa shortened the clotting time of patient samples, but CT-001 was superior to rFVIIa in all assays (Table 1). In clotting assays, CT-001 had potency higher than rFVIIa by ~2-fold in PT, and 6-8 fold in APTT. In TGA assays, CT-001 had potency higher than rFVIIa by 3-4 fold in the shortening of Lag Time and Time-to-Peak (TtP) parameters.
Conclusion: The enhanced procoagulant activity of CT-001 observed in this study together with the previously reported rapid clearance and low thrombogenicity of CT-001 in pre-clinical studies suggest that CT-001 has the potential for being an efficacious therapy for severe PPH with increased safety over rFVIIa.
Derek S. Sim, PhD
Chief Scientific Officer
Coagulant Therapeutics
Berkeley, California, United States
Terry W. Hermiston, PhD
Coagulant Therapeutics
Berkeley, California, United States
Terrence K. Allen, MBBS
Duke University
Durham, North Carolina, United States
Daekyeong Bae, PhD
Coagulant Therapeutics
Seoul, Seoul-t'ukpyolsi, Republic of Korea
Jennifer Gilner, MD,PhD
Assistant Professor of Obstertics and Gynecology
Duke University
Durham, North Carolina, United States
Seung-Chul Kim, MD, PhD
Pusan National University Hospital
Pusan, Pusan-jikhalsi, Republic of Korea
Sul Lee, MD
Pusan National University Hospital
Pusan, Pusan-jikhalsi, Republic of Korea
Cornell R. Mallari, BSc
Coagulant Therapeutics
Berkeley, California, United States
Andra H. James, MD, MPH
Professor Emeritus
Duke University Medical Center
Durham, North Carolina, United States