Emicizumab for Severe Von Willebrand Disease (VWD) and VWD/Hemophilia A (BCDI-XII)

March 30, 2026 updated by: Jonathan Roberts, Bleeding and Clotting Disorders Institute Peoria, Illinois

Emicizumab for Severe VON Willebrand Disease (VWD) and VWD/Hemophilia A

Von Willebrand Disease (VWD) is the most common inherited bleeding disorder affecting up to 0.1% of the population, is usually characterized by mucocutaneous bleeding, HMB, surgical bleeding or other hemostatic challenges. Severe bleeding events require VWF concentrates administered solely through intravenous access. Emicizumab (Hemlibra) is a monoclonal bispecific antibody developed to bind activated FIX and FX and mimic FVIII cofactor functionality. Hemlibra is administered via subcutaneous injection rather than intravenous infusion. The hypothesis of this study is that Emicizumab is safe and efficacious for prophylaxis in severe VWD and concomitant VWD/hemophilia patients.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Von Willebrand Disease (VWD) is the most common inherited bleeding disorder affecting up to 0.1% of the population, is usually characterized by mucocutaneous bleeding, HMB, surgical bleeding or other hemostatic challenges. VWD currently has few therapies generally useful in management of bleeding events including antifibrinolytics, desmopressin (DDAVP), and VWF concentrates, which may be plasma-derived (VWF with and without FVIII) or recombinant. Minor bleeding may be successfully treated with antifibrinolytics and DDAVP; however, more severe bleeding requires VWF concentrates that are administered solely through intravenous access.

Similarly, it can be challenging to treat concomitant bleeding disorders with the existing therapeutic options available, and patients with concurrent VWD and hemophilia A primarily have VWF/FVIII concentrate or desmopressin (DDAVP) available for treatment. It has been well-recognized that patients, caregivers, and medical providers desire additional, simplified therapeutic options that are not intravenous to treat severe bleeding disorders. Therefore, a simplified, subcutaneous therapeutic that prevents bleeding would be strongly desired. Though its use in the hemophilia A population is growing, additional potential emicizumab applications for hemostatic control in other hemostatic disorders remain unknown. A recent case report highlighted the hemostatic efficacy of emicizumab off-label use in type 3 von Willebrand Disease (VWD), another severe bleeding disorder. This pediatric patient had type 3 VWD with alloantibodies and a bleeding phenotype similar to hemophilia A with inhibitor patients, requiring suboptimal bleeding management with rFVIIa and activated prothrombin complex concentrates (aPCC). Emicizumab prophylaxis was initiated and the patient no longer required aPCC prophylaxis and rare use of rFVIIa for acute bleeding events (only 1 trauma-induced soft tissue hematoma at the time of publication). The authors concluded their report suggested the bleeding phenotype in type 3 VWD is expressed mainly due to factor VIII deficiency. This study suggests a potential additional application for emicizumab in severe VWD.

A pilot multicenter, prospective open-label study of emicizumab prophylaxis in severe VWD and concomitant VWD/hemophilia A. Patients will have a one-year retrospective chart review of annualized bleed rate and hemostatic therapies collected at the time of enrollment. Patients will then be treated with emicizumab with 3mg/kg weekly for 4 weeks loading dose, followed by once weekly prophylaxis of 1.5mg/kg for 1 year. Per emicizumab FDA-approved prescribing information for hemophilia A, dose up-titration to 3 mg/kg once weekly will be allowed after 24 weeks on HEMLIBRA prophylaxis in case of suboptimal efficacy (i.e., ≥ 2 spontaneous and clinically significant bleeds) Treatment records will be maintained along with bleeding event logs. Breakthrough bleeding events may be treated with the patients usual on-demand therapy with antifibrinolytics or VWF/FVIII concentrates per clinician discretion. Patient reported outcome assessments will be collected throughout the clinical study to collect impact of the treatment on the individual patients, assessing quality of life, physical, emotional, social and general symptoms.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Megan L Woodbury, PhD
  • Phone Number: 174 309-692-5337
  • Email: meganw@ilbcdi.org

Study Contact Backup

Study Locations

  • United States
    • California
      • Orange, California, United States, 92868
        • Recruiting
        • The Center for Comprehensive Care and Diagnosis of Inherited Blood Disorders (CIBD)
        • Contact:
        • Contact:
        • Principal Investigator:
          • Vanessa Salinas, MD
      • Redwood City, California, United States, 94063
        • Recruiting
        • Stanford University: Stanford Children's Health
        • Principal Investigator:
          • May Chien, MD
        • Contact:
        • Contact:
    • Florida
      • Coral Gables, Florida, United States, 33146
        • Recruiting
        • University of Miami - Miller School of Medicine
        • Contact:
        • Contact:
        • Principal Investigator:
          • Fernando Francisco Corrales-Medina, MD
      • Tampa, Florida, United States, 33607
    • Illinois
      • Peoria, Illinois, United States, 61614
        • Recruiting
        • Bleeding and Clotting Disorders Institute (BCDI)
        • Principal Investigator:
          • Jonathan C Roberts, MD
        • Sub-Investigator:
          • Michael D Tarantino, MD
        • Contact:
        • Contact:
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Recruiting
        • Innovative Hematology, Inc. (IHI)
        • Contact:
        • Contact:
        • Principal Investigator:
          • Sweta L Gupta, MD
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
      • Mount Pleasant, Michigan, United States, 48859
        • Recruiting
        • Central Michigan University: Children's Hospital of Michigan
        • Principal Investigator:
          • Meera Chitlur, MD
        • Contact:
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • Children's Mercy Hospital
        • Contact:
        • Principal Investigator:
          • Shannon L Carpenter, MD
    • Pennsylvania
    • Washington
      • Seattle, Washington, United States, 98101
    • Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 90 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Signed informed consent
  • Age 0 and older (infants weighing ≥3 kg)
  • ability to comply with protocol in investigators judgement
  • diagnosis of: severe VWD type 3, or VWD with VWF antigen, activity or collagen binding </= 20 U/dl or variant VWD confirmed by genetic mutation and VWF ag, activity or CB < 50 U/dl based on historical medical records of study site.
  • diagnosis of VWD/hemophilia A defined as VWF:ag, activity or CB <50 U/dl, and mild moderate or severe hemophilia A(defined by ISTH criteria) based on historical medical records of the study site.
  • plan to be adherent to emicizumab prophylaxis during the study
  • Patient's bleeding phenotype necessitating prophylaxis per treating provider recommendations.
  • Patient on current prophylaxis for VWD or VWD/hemophilia A may enroll if they are currently on a non-emicizumab agent, and if it has been > 18 months since last off-label dose of emicizumab, and are willing to discontinue current prophylaxis.
  • For menstruating individuals: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the study period. A menstruating individual is considered to be of childbearing potential if they are post-menarchal, have not reached a postmenopausal state (12 continuous months of amenorrhea with no identified cause other than menopause), and have not undergone surgical sterilization (removal of ovaries and/or uterus).

Examples of highly effective contraceptive methods with a failure rate of < 1% per year include proper use of combined oral or injected hormonal contraceptive, bilateral tubal ligation, male sterilization, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

  • Patients and/or infants weighing < 3 kg.
  • Patients with low VWF or non-severe VWD (ie.not meeting the above criteria)
  • Other concomitant bleeding disorders including coagulopathy from liver cirrhosis.
  • Current treatment with emicizumab or emicizumab therapy in the previous 18 months.
  • Previous (in the past 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or current signs of thromboembolic disease
  • Other conditions (e.g., certain autoimmune diseases, including, but not limited to diseases such as systemic lupus erythematosus, inflammatory bowel disease, and antiphospholipid syndrome) that may increase the risk of bleeding or thrombosis
  • Patients who are at high risk for thrombotic microangiopathy (TMA; e.g., have a previous medical or family history of TMA), in the investigator's judgment
  • Would refuse treatment with blood or blood products, if necessary.
  • Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
  • Treatment with any of the following:

An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration before Study Day 1 A non-hemophilia-related investigational drug within the last 30 days or 5 halflives- before Study Day 1, whichever is longer An investigational drug concurrently

  • History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
  • Pregnant or lactating, or intending to become pregnant during the study
  • Women of childbearing potential must have a negative serum pregnancy test result within 7 days before Study Day 1
  • Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
  • Serious infection requiring oral or IV antibiotics within 30 days prior to screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Open Label Emicizumab
Emicizumab prophylaxis
Drug: Emicizumab
Subcutaneous injection of emicizumab for prophylaxis
Other Names:
  • Hemlibra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Emicizumab is efficacious for prophylaxis in severe VWD & concomitant VWD/hemophilia A
Time Frame: 18 months
Establish bleed occurrence during treatment evaluated through descriptive statistical analysis to determine proof of principle
18 months
Emicizumab is safe for prophylaxis in severe VWD & concomitant VWD/Hemophilia A
Time Frame: 18 months
Collection of AE's, hypersensitivity reactions, thrombotic events during treatment
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Decreased bleed occurrence
Time Frame: 12 months
Evaluate historical ABR with on demand or prophy prior to study treatment
12 months
Reduced treatment burden vs VWF/FVIII prophylaxis
Time Frame: 18 months
# of infusions and methods of infusions collected during study
18 months
Diminish bleed severity
Time Frame: 18 months
Collection of bleed data prior to study entry and throughout study treatment
18 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reduce self-reported treatment burden for HMB
Time Frame: 18 months
Bleed & treatment logs collect treatment information prior to and during study for HMB including antifibrinolytics, concentrates and hormonal therapies.
18 months
Improve health related QOL in study participants
Time Frame: 18 months
Collection of HRQOL PRO's
18 months
Reduce product use for spontaneous or traumatic bleeds
Time Frame: 18 months
Bleed & treatment logs collecting product use prior to study entry and throughout study treatment
18 months
Reduce product use during surgery
Time Frame: 18 months
Bleed & treatment logs collect information for any surgical procedure while on study, blood loss, hemostatic efficacy and concentrate consumption.
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bleeding and Clotting Disorders Institute Peoria, Illinois

Collaborators

Genentech, Inc.

Investigators

  • Principal Investigator: Jonathan C Roberts, MD, Bleeding and Clotting Disorders Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2022

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

February 1, 2028

Study Registration Dates

First Submitted

August 12, 2022

First Submitted That Met QC Criteria

August 12, 2022

First Posted (Actual)

August 15, 2022

Study Record Updates

Last Update Posted (Actual)

April 3, 2026

Last Update Submitted That Met QC Criteria

March 30, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BCDI-XII

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Von Willebrand Disease, Type 3

Clinical Trials on Emicizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bahamas

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe