Table 2.

Published Phase I Trial for FXI Inhibitors

Registration Number	Patient Characteristics	Study		Drug Name			N		Endpoints		Conclusion
Antibodies
NCT03097341	Healthy adult volunteers aged 18–48 yo	Lorentz et al 201939		Xisomab 3G3 (AB023)			21 N=16 active N= 5 placebo		Safety (Abnormal Vital Signs, Abnormal Electrocardiogram, Abnormal Injection Site Reaction, Abnormal Laboratory Values, Immunogenicity, death) Tolerability Pharmacokinetic parameters Pharmacodynamic parameters		There were no serious adverse events (SAEs) experienced in this study. No subjects were removed from the study due to adverse events (AEs). Overall, 10 of 21 (48%) subjects experienced a total of 20 TEAEs in this study, with 7 of 16 (44%) subjects following active treatment and 3 of 5 (60%) subjects following placebo
/	ANT-003 Healthy adult volunteers + obese patients (BMI ≥ 35 kg/m2) aged 18-60 yo ANT-004 patients with atrial fibrillation or flutter CHA2DS2-VASc of 0–1 for men and 1–2 for women aged 18–85 yo	Yi et al 202240 ANT-003 ANT-004		Abelacimab (MAA868)			32 ANT-003=24 ANT-004=8		As vital signs, adverse event assessments, laboratory tests, Pharmacokinetic parameters Pharmacodynamic parameters Anti-drug antibodies (ADA) assessment		The limitations of these studies include, by design, the single dose exposure in ANT-003 which limits the ability to detect clinically relevant safety signals. In addition, due to the COVID-19 pan -demic, enrollment in the ANT-004 study was stopped early and thus the fully planned data set of PK, PD, and immunogenicity data for monthly subcutaneous administration of abelacimab could not be collectedParenteral administration of abelacimab demonstrated a fa-vorable safety profile with no clinically relevant bleeding events
Antisens oligonucleotides or ASO
/	Healthy subjects aged 18–65 yo	Liu et al. 201157		ISIS-FXIRx			Single dose SC 50 mg/kg n=8 100 mg/kg n=8 200 mg/kg n=16 300 mg/kg n=8 8x SC injections n=12		Safety (adverse event (AE) clinical and laboratory tests safety, tolerability, pharmacokinetics and pharmacodynamics		No study drug related bleeding events were reported. No clinical or biological significant modification occured One serious AE (allergic reaction) occured
Small molecule
NCT03919890	Part A enrolled men only, Part B enrolled men or women of non-childbearing potential aged 18–55 yo	Beale et al 202158		ONO-7684			72 Part A n= 36 active n= 12 Part B n=24		Safety (adverse event (AE) reporting using the Medical Dictionary for Regulatory Activities (version 22.0), clinical laboratory tests (biochemistry, haematology and urinalysis), vital signs, electrocardiograms (ECGs), physical examination and cardiac telemetry) Tolerability Pharmacokinetic parameters Pharmacodynamic parameters		No signal on safety total of eight (16.7%) out of 48 fasted subjects and one (12.5%) out of eight fed subjects reported treatment-emergent adverse events (TEAEs) in Part A, and three (12.5%) of 24 subjects reported TEAEs in Part B (Table 2). There were no severe or serious TEAEs and no TEAEs that led to treatment discontinuation or interruption.
/	Healthy adult caucasian men Aged 18–45 yo	Thomas et al 202159		Asundexian (BAY2433334)			70 Part 1 n=56 active n=14 placebo; Part 2 n=16		Safety (symptomatic bleeding, signs of hepatobiliary dysfunction or pancreatic disorders, Tolerability Pharmacokinetic parameters Pharmacodynamic parameters		BAY 2433334 exhibited favorable safety and tolerability. BAY 2433334 dose-dependently inhibited FXIa activity and increased activated partial thromboplastin time.
/	Healthy adult caucasian men Aged 18–45 yo	Kubitza et al 202238		Asundexian (BAY2433334)			96 Parts A and B: n= 36 active; n=12 to placebo. Part C: n= 48 active plus midazolam		Safety (physical examination, vital signs, 12-lead electrocardiogram (ECG) and clinical laboratory evaluation) Tolerability Pharmacokinetic parameters Pharmacodynamic parameters Interaction with Midazolam		Multiple dosing of BAY 2433334 in healthy volunteers was well tolerated, with a predictable pharmacokinetic/pharmacodynamic profile and no clinically relevant CYP3A4 induction or inhibition.
/	Healthy adult volunteers: Aged 18–45 yo	Perera et al 202137		Milvexian (BMS-986177) (JNJ70033093)			48 part A of the study (n = 24 active, n = 8 placebo). Part B (n = 32 active, n = 8 placebo)		Safety a medical review of adverse event (AE) reports and the results of clinical laboratory tests, vital sign measurements, ECGs, and physical examinations up to 48 h postdose. Events of special interest included clinically and nonclinically significant bleeding. AEs were coded according to the Medical Dictionary for Regulatory Activities (MedDRA), version 20.0. Pharmacokinetic parameters Pharmacodynamic parameters		Administration were generally safe and well-tolerated. No deaths or other Severe AEs occurred during the study. All Treatment-emergent AEs were mild in severity.