This is a first-in-human (FIH), Phase 1/2, 3-part open-label, dose escalation, safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and efficacy study evaluating HMB-002 in participants with VWD. Part A of the study involves a single ascending dose (SAD) regimen design to establish safety, tolerability, PK, and PD effect. In Part B of the study, the safety and tolerability of repeat dosing will be established prior to cohort expansion to explore efficacy. Part C will evaluate the safety, PK, and PD of a single concomitant dose of HMB-002 and factor concentrate with Type 3 VWD or Type 1 VWD with low residual VWF and FVIII who use factor concentrate as prophylaxis.
Weight 50 to 120 kg, inclusive.
Documented diagnosis of Congenital VWD, confirmed by laboratory testing consistent with ISTH/ASH) diagnostic guidelines).
Vital signs are within normal ranges at Screening.
Renal: Estimated glomerular filtration rate (eGFR) of ≥45 mL/min/1.73m².
Personal history of venous or arterial thrombosis or thromboembolic disease, except for catheter-associated, superficial venous thrombosis.
High risk thrombophilia: Homozygous Factor V Leiden (FVL), compound heterozygous FVL/Prothrombin gene mutation, Antithrombin deficiency with activity <50%. Congenital Protein C and Protein S deficiency with levels <50%.
Body mass index (BMI) >35 kg/m² (obese, adjusted for ethnicity).
Presence of other conditions that substantially increase risk of thrombosis either individually (for participants >65 years of age) or in combination (for participants ≤65 years of age), at the discretion of the Investigator or Medical Monitor.