A Study Assessing HMB-002 in Participants With Von Willebrand Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Von Willebrand Disease (VWD); Von Willebrand Disease (VWD), Type 1; Von Willebrand Disease (VWD), Type 2; Von Willebrand Disease (VWD), Type 3
• Intervention / Treatment: Drug: HMB-002 (Part A); Drug: HMB-002 (Part B); Drug: HMB-002 with Concomitant Factor Concentrate (Part C) (Not Applicable in US)

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials; Phone Number: 080 8304 6409; Email: clinicaltrials@hemab.com

Study Locations

• Australia
  • Perth
    • Murdoch, Perth, Australia, WA 6150
      • Not yet recruiting
      • Fiona Stanley Hospital
  • Sydney
    • Camperdown, Sydney, Australia, NSW 2050
      • Recruiting
      • Royal Prince Alfred Hospital
  • Victoria
    • Melbourne, Victoria, Australia, VIC 3004
      • Recruiting
      • The Alfred Hospital
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Not yet recruiting
    • University Hospitals Birmingham NHS Foundation Trust
  • Cardiff, United Kingdom, CF14 4XW
    • Recruiting
    • University Hospital of Wales
  • Leeds, United Kingdom, LS9 7TF
    • Not yet recruiting
    • St James's University Hospital, Leeds Haemophilia Centre
  • Liverpool, United Kingdom, L7 8XP
    • Not yet recruiting
    • Royal Liverpool and Broadgreen University Hospitals NHS TRUST, The Roald Dahl Haemostasis and Thrombosis Centre
  • London, United Kingdom, SE1 1YR
    • Recruiting
    • Richmond Pharmacology
  • London, United Kingdom, SE1 7EH
    • Not yet recruiting
    • St Thomas' Hospital
  • Hampshire
    • Basingstoke, Hampshire, United Kingdom, RG24 9NA
      • Recruiting
      • Basingstoke and North Hampshire Hospital
  • London
    • Tooting, London, United Kingdom, SW17 0QT
      • Not yet recruiting
      • St George's Hospital
    • Whitechapel, London, United Kingdom, E1 1FR
      • Not yet recruiting
      • Royal London Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Not yet recruiting
      • Phoenix Children'S Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Not yet recruiting
      • Arkansas Children's Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Not yet recruiting
      • Children's Hospital of Los Angeles
  • Florida
    • Miami, Florida, United States, 33136
      • Not yet recruiting
      • University of Miami Hospital and Clinics, Sylvester Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Not yet recruiting
      • Emory Children's Center
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Recruiting
      • Innovative Hematology, Inc./Indiana Hemophilia and Thrombosis Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Not yet recruiting
      • Tulane University School of Medicine
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Not yet recruiting
      • University of Michigan Hospitals, Department of Hemophilia and Coagulation Disorders
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Not yet recruiting
      • Mayo Clinic - Rochester
  • Oregon
    • Portland, Oregon, United States, 97239
      • Not yet recruiting
      • Oregon Health & Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Not yet recruiting
      • Hemophilia Center of Western Pennsylvania
  • Texas
    • Dallas, Texas, United States, 75390
      • Not yet recruiting
      • The University of Texas Southwestern Medical Center
  • Washington
    • Seattle, Washington, United States, 98101
      • Not yet recruiting
      • Washington Institute For Coagulation (WIC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Weight 50 to 120 kg, inclusive.
2. Documented diagnosis of Congenital VWD, confirmed by laboratory testing consistent with ISTH/ASH) diagnostic guidelines).
3. Vital signs are within normal ranges at Screening.

4. Participants must meet the following baseline organ function, indicated by laboratory criteria as Screening:

   1. Renal: Estimated glomerular filtration rate (eGFR) of ≥45 mL/min/1.73m^2.
   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.
   3. Hematology >85 g/L and platelet count >120 x 10^9/L.

   Part A Only:

5. Age: ≥18 and <70 years of age at the time of informed consent.

6. 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

7. Residual VWF activity of ≤ 50 IU/dL and FVIII activity ≤ 70 IU/dL during screening.

   Part B Only:

8. Age: ≥16 and <70 years of age at the time of informed consent.
9. VWD Subtype Eligibility: Participants with Type 1 VWD (including Type 1C) and Type 2A.
10. Residual VWF activity of ≤50 IU/dL and FVIII activity ≤70 IU/dL during screening.
11. Symptomatic Disease: Participants must be symptomatic, typically reporting bleeding events on a monthly basis.

12. Bleeding History (must meet one of the following):

    1. 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

    2. 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:

13. Age: ≥18 and <70 years of age at the time of informed consent.
14. 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).
15. Receives regular VWF concentrate (at least 1/week) as part of their routine care (usual dose ≤50 IU/kg).

Key Exclusion Criteria:

1. Personal history of venous or arterial thrombosis or thromboembolic disease, except for catheter-associated, superficial venous thrombosis.
2. 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%.
3. Body mass index (BMI) >35 kg/m^2 (obese, adjusted for ethnicity).
4. 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.
5. Clinically significant cardiovascular disease.
6. Other known severe bleeding disorder(s) other than VWD.

7. Requirement for concomitant medications that affect hemostasis (including, but not limited to anticoagulation, antiplatelet agents, certain non-steroidal anti-inflammatory drugs) and cannot refrain from use for 14 days prior to the first dose of study drug and throughout the study.

   Exclusion Criteria for Part A and Part B Only

8. Requirement for ongoing hemostatic treatment to prevent bleeding (bleed prophylaxis). Prophylaxis administered intermittently for procedures or surgery to reduce bleeding risk is permitted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A Single Ascending Dose Design; A multicenter study to evaluate the safety, tolerability, PK, and PD effect of single dose HMB-002 in participants with Type 1 VWD.	Drug: HMB-002 (Part A); HMB-002 will be administered subcutaneously. Part A will utilize sentinel dosing. The planned duration of study participants in Part A is approximately 12 weeks.
Experimental: Part B Multiple Dose Assessment; A multicenter study to evaluate the safety, tolerability, PK, and PD effect of repeat doses of HMB-002, as well as the preliminary prophylactic effects on bleeding events.	Drug: HMB-002 (Part B); HMB-002 will be administered subcutaneously. Part B dosing intervals will be determined following evaluation of Part A results. The planned duration of study participants in Part B will be approximately 21 weeks.
Experimental: Part C HMB-002 with Concomitant Factor Concentrate; A multicenter study to evaluate the safety and tolerability of a single dose of HMB-002, administered to patients concurrently receiving regular factor concentrate as standard of care.	Drug: HMB-002 with Concomitant Factor Concentrate (Part C) (Not Applicable in US); HMB-002 will be administered as a single dose with a concomitant single dose of factor concentrate. The planned duration of study participants in Part C will be approximately 17 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Treatment emergent adverse events (TEAE)	up to Day 113

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic Parameter: Maximum observed plasma concentration (Cmax)	Day 1 to Day 113
Pharmacokinetic Parameter: Area under the curve from time zero to last quantifiable concentration (AUClast)	Day 1 to Day 113
Pharmacokinetic Parameter: Area under the curve from time zero to extrapolated infinite time (AUCinf)	Day 1 to Day 113
Pharmacokinetic Parameter: Time to reach maximum observed plasma concentration (Tmax)	Day 1 to Day 113
Pharmacodynamics Parameters: Assessment of VWF antigen (VWF:Ag)	Day 1 to Day 113
Pharmacodynamics Parameters: Assessment of VWF activity	Day 1 to Day 113
Pharmacodynamics Parameters: Assessment of FVIII activity	Day 1 to Day 113
Annualized Bleeding Rate Assessments	Day 1 to Day 113
Pharmacokinetic Parameter: Terminal elimination half-life (t1/2)	Day 1 to Day 113

Collaborators and Investigators

• Sponsor: Hemab ApS

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: December 19, 2024
• First Submitted That Met QC Criteria: December 23, 2024
• First Posted (Actual): January 1, 2025

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Von Willebrand Disease (VMD); Type 1 VWD; Von Willebrand Factor (VWF); Type 2 VWD; Type 3 VWD; Type 1 with low residual VWF and FVIII who use factor concentrate as prophylaxis
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Platelet Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; von Willebrand Diseases; von Willebrand Disease, Type 3
• Other Study ID Numbers: HMB-002-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No