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, 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.
• 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) at Screening. For participants with a history of Gilbert's Syndrome, total bilirubin ≤2 × ULN.
‣ Hematology \>85 g/L and platelet count \>120 x 10\^9/L.
• Part A Only:
• Age: ≥18 and \<70 years of age at the time of informed consent.
• VWD Subtype Eligibility:
‣ Cohorts A1 and A2: Participants with Type 1 VWD, only.
⁃ Cohorts A3 and A4: Participants with Type 1 VWD (including Type 1C) and Type 2A VWD
• Residual VWF activity of ≤ 50 IU/dL and FVIII activity ≤ 70 IU/dL during screening.
• Part B Only:
• Age: ≥16 and \<70 years of age at the time of informed consent.
• VWD Subtype Eligibility: Participants with Type 1 VWD (including Type 1C) and Type 2A.
⁃ Residual VWF activity of ≤50 IU/dL and FVIII activity ≤70 IU/dL during screening.
⁃ Symptomatic Disease: Participants must be symptomatic, typically reporting bleeding events on a monthly basis.
⁃ Bleeding History (must meet one of the following):
• Prior Observational Study Participation:
• The participant must have participated in the observational study HMB-002-101\_SCR (VELORA Discover), have a minimum annualized treated bleeding event (ATBR) of 3; OR
∙ Medical Record-Documented Bleeding History:
⁃ The Investigator confirms that ≥3 treated bleeding events have been documented in the participant's medical record within the preceding 12 months.
⁃ Part C Only:
⁃ Age: ≥18 and \<70 years of age at the time of informed consent.
⁃ Participants with Type 3 VWD or Type 1 VWD with low residual VWF and FVIII activity levels (VWF activity \<5 IU/dL and FVIII activity \<10 IU/dL).
⁃ Receives regular VWF concentrate (at least 1/week) as part of their routine care (usual dose ≤50 IU/kg).