Clinical trial NCT06754852: A Study Assessing HMB-002 in Participants With Von Willebrand Disease
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Von Willebrand Disease (VWD)
Von Willebrand Disease (VWD), Type 1
Keywords: Von Willebrand Disease (VMD)
Type 1 VWD
Von Willebrand Factor (VWF)
Lead sponsor: Hemab ApS
Sponsor class: INDUSTRY
First posted: 2025-01-01
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Treatment emergent adverse events (TEAE)
timeFrame: up to Day 113
Secondary outcomes:
measure: Pharmacokinetic Parameter: Maximum observed plasma concentration (Cmax)
timeFrame: Day 1 to Day 113
measure: Pharmacokinetic Parameter: Area under the curve from time zero to last quantifiable concentration (AUClast)
timeFrame: Day 1 to Day 113
measure: Pharmacokinetic Parameter: Area under the curve from time zero to extrapolated infinite time (AUCinf)
timeFrame: Day 1 to Day 113
measure: Pharmacokinetic Parameter: Time to reach maximum observed plasma concentration (Tmax)
timeFrame: Day 1 to Day 113
measure: Pharmacodynamics Parameters: Assessment of VWF antigen (VWF:Ag)
timeFrame: Day 1 to Day 113
measure: Pharmacodynamics Parameters: Assessment of VWF activity
timeFrame: Day 1 to Day 113
measure: Pharmacodynamics Parameters: Assessment of FVIII activity
timeFrame: Day 1 to Day 113
measure: Annualized Bleeding Rate Assessments
timeFrame: Day 1 to Day 113
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Richmond Pharmacology
Study officials:
References: