A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CITY-FXI in Healthy Adults, Adults With FV Leiden or Prothrombin G20210A Mutation, and Adults With a History of Provoked Venous Thromboembolism

This is a first-in-human (FIH), single-center, randomized, double-blind, placebo-controlled, single ascending and multiple dose study evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CITY-FXI in healthy adults, adults with Factor V Leiden (FVL) or prothrombin G20210A mutation, and adults with a history of provoked venous thromboembolism (VTE).

Inclusion Criteria: * Males and women of non-childbearing potential (WONCBP) aged 18 to 45 years (inclusive, for Part A only) * Male and female participants aged 18 to 60 (inclusive, for Part B only), and aged 18 to 65 years (inclusive, for Part C only) * Body Mass Index (BMI) between 18 and 25 kg/m2 (inclusive, for Parts A and B only) and 18 and 35 kg/m2 (inclusive, for Part C only) and a minimum weight of 50 kg (Parts A, B, and C) * Ability and willingness to comply fully with all study procedures and lifestyle considerations * Confirmed diagnosis of FVL or prothrombin G20210A mutation via genetic testing (Part B only) * Women of childbearing potential (WOCBP) must agree to use acceptable highly effective contraceptive methods (Parts B and C only) * History of provoked venous thromboembolism (VTE) within the last 10 years and/or confirmed diagnosis of heterozygosity for FVL or prothrombin G20210A mutation via genetic testing (Part C only) Exclusion Criteria: * Any clinically significant systemic disease or disorder, including but not limited to cardiovascular, hepatic, or oncological conditions * History or evidence of any bleeding disorders * History of clinically significant spontaneous bleeding * Prior treatment with an investigational agent * Confirmed diagnosis of homozygous mutations, or combined thrombophilic defects (e.g., FVL with prothrombin G20210A mutation) (Parts B and C only)