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

Phase 1

Recruiting

• Conditions: Von Willebrand Disease (VWD); Von Willebrand Disease (VWD), Type 1
• Interventions: Drug: HMB-002 (Part A); Drug: HMB-002 (Part B)

• Registration Number: NCT06754852
• Lead Sponsor: Hemab ApS

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-12-19
• Study First Submitted QC: 2024-12-23
• Study First Posted: 2025-01-01
• Study Start: 2025-02-06
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-03
• Last Update Posted: 2025-03-06
• Primary Completion: 2027-07
• Study Completion: 2027-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 108

Inclusion Criteria

1. Has the ability to provide informed consent to participate in the study, in accordance with applicable regulations.

2. Has an understanding, ability, and willingness to comply with study procedures and restrictions.

3. ≥18 and <65 years.

4. Weight 60 to 110 kg, inclusive.

5. Congenital Type 1 VWD diagnosis as documented by laboratory results for VWF antigen and activity.

6. Vital signs are within the following ranges at Screening:

   1. Resting pulse rate ≤105 bpm

   2. Blood pressure (BP):

      • Systolic blood pressure: 90 - 140 mmHg
      • Diastolic blood pressure: 40 - 90 mmHg

7. 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.

8. 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.

9. 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) range at Screening. For participants with a history of Gilbert's Syndrome, total bilirubin ≤2 × ULN.
   3. Hematology: Hemoglobin >85 g/L and platelet count >120 x 10^9/L.

10. 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.

Exclusion Criteria

1. History of clinically significant hypersensitivity associated with monoclonal antibody therapies.
2. Personal history of venous or arterial thrombosis or thromboembolic disease, except for catheter-associated, superficial venous thrombosis.
3. High risk thrombophilia: Homozygous Factor V Leiden (FVL), compound heterozygous FVL/Prothrombin gene mutation, Antithrombin <50%. Congenital Protein C and Protein S deficiency with levels <50%.
4. Requires ongoing bleed prophylaxis with IV factor concentrates.
5. Has a positive test for Hepatitis B surface antigen (HbsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at Screening with RNA level above the lower limit of detection.
6. Has received any live vaccine within 28 days prior to signing of informed consent and/or is planning to have a live vaccine during the study period.
7. Planned major surgery during the course of the study.
8. Body mass index (BMI) >35 kg/m^2 (obese, adjusted for ethnicity).
9. Other conditions that substantially increase risk of thrombosis by the discretion of the Investigator.
10. Participants who are pregnant or breastfeeding.
11. Clinically significant cardiovascular disease.
12. Other conditions that substantially increase the risk of cardiovascular events by the discretion of the Investigator.
13. Congenital or acquired bleeding disorders other than Type 1 VWD.
14. Concurrent disease, treatment, medication, or abnormality in clinical laboratory tests may pose additional risk in the opinion of the investigator.
15. Hypersensitivity to study drug or any of the excipients.
16. Received investigational medication in another clinical study within 5 half-lives before administration of HMB-002.
17. PART A only: Type 1C VWD.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A Single Ascending Dose Design	HMB-002 (Part A)	A multicenter study to evaluate the safety, tolerability, PK, and PD effect of single dose HMB-002 in participants with Type 1 VWD.
Part B Multiple Dose Assessment	HMB-002 (Part B)	A multicenter study to evaluate the safety, tolerability, PK, and PD effect of 3 repeat doses of HMB-002, as well as the preliminary prophylactic effects on bleeding events.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment emergent adverse events (TEAE)	up to Day 113

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Richmond Pharmacology; 🇬🇧 London, United Kingdom