A Study of Bleeding and Treatment in Participants With Von Willebrand Disease

Recruiting

• Conditions: Von Willebrand Disease (VWD); Von Willebrand Disease, Type 3; Von Willebrand Disease, Type 2B; Von Willebrand Disease (VWD), Type 1; Von Willebrand Disease (VWD), Type 2 and Type 3
• Interventions: Other: Clinical outcomes of patients with VWD, Type 2 and Type 3; Other: Clinical outcomes of patients with VWD, Type 1 (less than 30 IU per dL); Other: Clinical outcomes of patients with VWD, Type 1 (less than 50 IU per dL)

• Registration Number: NCT06610201
• Lead Sponsor: Hemab ApS

Brief Summary

The purpose of this screening study is to accumulate information regarding bleeding events, quality of life, and the social and clinical impact of bleeds in participants with Von Willebrand Disease (VWD). Data from this study will be used to establish baseline bleeding and treatment rates in a population of participants with VWD and act as comparator data for future clinical study outcomes.

Detailed Description

This is a prospective, screening study in a minimum of 100 participants with confirmed Type 1 VWD according to diagnostic guidelines. Participants with Type 1 VWD and a residual Von Willebrand Factor (VWF) antigen and/or activity of less than 40 IU per dL will be prioritized for recruitment. After approximately 50 participants with a residual VWF antigen and/or activity of less than 40 IU per dL have been included, participants with Type 1 VWD diagnosis and a residual VWF antigen and activity of less than 50 IU per dL may be screened for inclusion. Following enrollment of 100 participants with Type 1 VWD, the study may be opened to participants with Type 2 and Type 3 VWD.

The study includes screening, a Baseline evaluation, and a 4-6 month observation period which will include every other week telemedicine check-ins (to monitor bleed diary and bleeding event treatments), and clinic visits every 12 weeks for laboratory draws. There will be an optional extension to the observation period of up to a total of 12 months for participants wishing to continue.

Study Timeline

• Study Start: 2024-08-30
• Study First Submitted: 2024-09-13
• Study First Submitted QC: 2024-09-23
• Study First Posted: 2024-09-24
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-06
• Last Update Posted: 2025-06-11
• Primary Completion: 2026-02
• Study Completion: 2026-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Has the ability to provide informed consent to participate in the study, in accordance with the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 (R2) (2016) and applicable national and international regulations, before any protocol directed interventions are carried out.

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

3. Is 16 years or older at the time of screening.

4. First approximately 50 participants: congenital Type 1 VWD with a residual VWF antigen and/or activity less than 40 IU/dL (40%)

   Next approximately 50 participants: Type 1 VWD with residual VWF antigen and activity less than 50 IU/dL (50%)

   After the first approximately 100 participants: congenital Type 1, Type 2A, Type 2M, Type 2N, or Type 3 VWD

   Note: Participants may be enrolled if they have documented laboratory results for VWF antigen and activity within their medical records confirming their diagnosis (consistent with International Society on Thrombosis and Hemostasis [ISTH]/American Society of Hematology [ASH] diagnostic guidelines or British Society for Haematology [BSH]/ United Kingdom Haemophilia Centre Doctors; Organisation [UKHCDO] diagnostic guidelines). For Type 1 VWD in the first part of the study, participants also need to have a documented laboratory result within the last 2 years showing a VWF antigen and/or activity level less than 40 IU/dL. Participants meeting eligibility criteria based on documented results will proceed with having samples collected at Screening to further characterize their antigen and activity levels. These may be repeated up to 2 further times if the results are not consistent with their documented diagnosis and levels are greater than 40 IU/dL.

   If participants do not have confirmed results in their medical records as described above, the screening assessment may be repeated up to 2 further times to establish baseline levels for inclusion.

5. Has symptomatic disease as defined by a history of bruising or bleeding events, and typically experiencing bleeding symptoms every month.

Exclusion Criteria

1. Has a personal history of venous or arterial thrombosis or thromboembolic disease, except for catheter-associated, superficial vein thrombosis events.
2. Has a significant family history of unprovoked thromboembolic events in first degree relatives.
3. Has a congenital or acquired bleeding disorder other than VWD.
4. Has planned major surgery within the next 6 months.
5. Is pregnant or plans to become pregnant within the next 6 months.
6. Has any concurrent disease, treatment (including ongoing anticoagulation, antiplatelet, or non-steroidal anti-inflammatory drugs), condition, medication, or abnormality in clinical laboratory tests which may impact on the participant's bleeding symptoms or affect their ability to complete the study, in the Investigator's opinion.
7. Has received any investigational product within 30 days prior to screening.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
VWD, Type 2 and Type 3	Clinical outcomes of patients with VWD, Type 2 and Type 3	-
VWD, Type 1 (residual VWF antigen and/or activity less than 30 IU per dL)	Clinical outcomes of patients with VWD, Type 1 (less than 30 IU per dL)	-
VWD, Type 1 (activity less than 50 IU per dL)	Clinical outcomes of patients with VWD, Type 1 (less than 50 IU per dL)	-

Primary Outcome Measures

Name	Time	Method
Annualized bleeding event rate	4.5 to 12.5 months
Annualized treated bleeding rate	4.5 to 12.5 months
Annualized heavy menstrual bleed rate	4.5 to 12.5 months
Number of overnight admissions	4.5 to 12.5 months	Hospitalization monitoring of bleeding events.

Secondary Outcome Measures

Name	Time	Method
Prophylactic and on demand treatment	4.5 to 12.5 months	Details of treatment used for bleeding events
Iron status	4.5 to 12.5 months	Blood samples will be collected for the determination of ferritin and hemoglobin.
Iron replacement use	4.5 to 12.5 months	Recording iron medication at baseline, changes in iron medication prescription and the indication for this change.
Patient-Reported Outcomes Measurement Information System (PROMIS)-29	4.5 to 12.5 months	An assessment which evaluates four items from each of the seven PROMIS domains. Each question is rated on a scale of 1 to 5. In addition, the PROMIS-29 includes one pain intensity question which is rated on a scale of 1 to 10. Higher scores on the PROMIS-29 indicate worse symptoms.
Menstrual Bleeding Questionnaire (MBQ)	4.5 to 12.5 months	Measure the effect of heavy menstrual bleeding on a self-assessment of menstrual blood loss, limitations in social and leisure activities, physical activities, and work activities.

Trial Locations

Locations (15)

Phoenix Children's Hospital; 🇺🇸 Phoenix, Arizona, United States

Innovative Hematology, Inc./Indiana Hemophilia and Thrombosis Center; 🇺🇸 Indianapolis, Indiana, United States

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

Emory Children's Center; 🇺🇸 Atlanta, Georgia, United States

The University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Washington Institute For Coagulation (WIC); 🇺🇸 Seattle, Washington, United States

Fiona Stanley Hospital; 🇦🇺 Murdoch, Perth, Australia

Royal Prince Alfred Hospital; 🇦🇺 Camperdown, Sydney, Australia

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

University of Miami Hospital and Clinics, Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

Richmond Pharmacology; 🇬🇧 London, United Kingdom

Tulane University School of Medicine; 🇺🇸 New Orleans, Louisiana, United States

University of Michigan Hospitals, Department of Hemophilia and Coagulation Disorders; 🇺🇸 Ann Arbor, Michigan, United States

Mayo Clinic - Rochester; 🇺🇸 Rochester, Minnesota, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States