A Phase 1/2 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of HMB-002 in Participants With Von Willebrand Disease (Velora Pioneer)
This is a first-in-human (FIH), Phase 1/2, open-label, dose escalation, safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and efficacy study of HMB-002 in participants with VWD. Part A of the study involves a single ascending dose (SAD) 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.
• Has the ability to provide informed consent to participate in the study, in accordance with applicable regulations.
• Has an understanding, ability, and willingness to comply with study procedures and restrictions.
• ≥18 and \<65 years.
• Weight 60 to 110 kg, inclusive.
• Congenital Type 1 VWD diagnosis as documented by laboratory results for VWF antigen and activity.
• Vital signs are within the following ranges at Screening:
∙ Resting pulse rate ≤105 bpm
‣ Blood pressure (BP):
⁃ Systolic blood pressure: 90 - 140 mmHg
• Diastolic blood pressure: 40 - 90 mmHg
• Participants assigned female at birth and of child-bearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose of HMB-002.
• Women of childbearing potential (CBP) and men with sexual partners of CBP must agree to use a medically acceptable method of contraception throughout the study.
• Participants must meet the following baseline organ function, indicated by laboratory criteria as Screening:
∙ Renal: Estimated glomerular filtration rate (eGFR) of ≥45 ml/min/1.73m\^2.
‣ Hepatic: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin ≤1.5 upper limit of normal (ULN) range at Screening. For participants with a history of Gilbert's Syndrome, total bilirubin ≤2 × ULN.
‣ Hematology: Hemoglobin \>85 g/L and platelet count \>120 x 10\^9/L.
⁃ PART B ONLY- Participants must be symptomatic as defined by a history of bleeding events. They must have participated in the observational study HMB-002-101\_SCR and have recorded bleeding events within this observational study.