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

Hemab

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Von Willebrand Disease (VWD), Type 2; Von Willebrand Disease (VWD), Type 1; Von Willebrand Disease (VWD)

Treatments: Drug: HMB-002 (Part A); Drug: HMB-002 (Part B)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06754852

HMB-002-102

Details and patient eligibility

About

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.

Enrollment: 108 estimated patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

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 50 to 110 kg, inclusive.

5. Congenital Type 1 VWD, Type 1C and Type 2A 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) must agree to use two medically acceptable methods of contraception throughout the study. Men with sexual partners of CBP must agree to use a condom please one additional method of contraception (used by their female partner) 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 (Hgb): Hemoglobin >85 g/L and platelet count >120 x 10^9/L.

10. PART B ONLY- Participants must be symptomatic (typically reporting bleeding events every month) with a minimum of 3 treated bleeding events reported in either the observational study HMB-002-101_SCR or in the participant's medical record.

11. Part B only: Participants may be enrolled if they have completed Part A follow-up.

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 hemostatic treatment to prevent bleeding, except prior to procedures/surgery.
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 either individually or in combination by the discretion of the Investigator.
10. Participants who are pregnant or breastfeeding.
11. Clinically significant cardiovascular disease.
12. Participants who are currently smoking and unable to refrain from cigarette/cigar/tobacco/vape smoking throughout the study duration.
13. Other conditions that substantially increase the risk of cardiovascular events by the discretion of the Investigator.
14. Congenital or acquired bleeding disorders other than Type 1, Type 1C, or Type 2A VWD.
15. Concurrent disease, treatment, medication (including but not limited to drugs that would affect hemostasis), or abnormality in clinical laboratory tests may pose additional risk in the opinion of the investigator.
16. Hypersensitivity to study drug or any of the excipients.
17. Received investigational medication in another clinical study within 5 half-lives before administration of HMB-002.
18. Requires the use of drugs that would 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

108 participants in 2 patient groups

Part A Single Ascending Dose Design

Experimental group

Description:

A multicenter study to evaluate the safety, tolerability, PK, and PD effect of single dose HMB-002 in participants with Type 1 VWD.

Treatment:

Drug: HMB-002 (Part A)

Part B Multiple Dose Assessment

Experimental group

Description:

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.

Treatment:

Drug: HMB-002 (Part B)