Von Willebrand Disease, Type 3Phase 3WILL-EMINCT06998524
A Study to Assess the Efficacy and Safety of Emicizumab in Participants With Type 3 Von Willebrand Disease
A Phase 3 study testing Emicizumab, von Willebrand Factor (VWF) Concentrates and Factor VIII (FVIII) Concentrates in people with Von Willebrand Disease, Type 3, run by Hoffmann-La Roche at 29 sites in 14 countries.
Trial summary
This is a Phase III, multicenter, open-label clinical study designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab prophylaxis in participants aged 1 month and above, who have been diagnosed with Type 3 von Willebrand disease (VWD). Read more about this study
- Who is it for?
- Ages 1 month and older
- Conditions the study is for
- Von Willebrand Disease, Type 3
- What is being tested?
- Emicizumab, von Willebrand Factor (VWF) Concentrates and Factor VIII (FVIII) Concentrates
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 29 sitesin 14 countries
- Study dates
- 27 Jun 2025to 30 Apr 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Confirmed diagnosis of Type 3 von Willebrand disease (VWD), based on medical records
- Preexisting medical record verifying the status of von Willebrand factor (VWF) inhibitor (positive or negative, including titer if available)
- Adequate hematologic, hepatic, and renal function
- For participants of childbearing potential: agreement to remain abstinent or adhere to the contraception requirements
- Additional Inclusion Criteria for Arms A and B:
- Age ≥1 month at the time of signing Informed Consent/Assent Form
Show all 12Show fewer
- Documented previous use of on-demand therapy with intermittent (less than once a week) on-demand SOC therapy for VWD
- Having ≥2 treated bleeds (except menstrual bleeds) with factor concentrate within 24 weeks prior to enrollment
- Additional Inclusion Criteria for Arm C:
- Age ≥2 years at the time of signing Informed Consent/Assent Form
- Documented and confirmed previous use of SOC prophylactic therapy for VWD (1-3 times weekly, as per prescribed dose) as described in the eligibility of Study WP45335
- Have completed all study requirements as defined in the WP45335 protocol for at least 24 weeks
Who cannot join
- Inherited or acquired bleeding disorder other than Congenital Type 3 VWD
- History of gastrointestinal bleeding within 18 months prior to enrollment, or any previous diagnosis of angiodysplasia
- History of intracranial hemorrhage
- Previous or current treatment for thromboembolic disease or signs of thromboembolic disease
- Other conditions (e.g., certain autoimmune diseases) that may increase risk of bleeding or thrombosis
- History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
- Use of systemic immunomodulators (e.g., interferon) at enrollment or planned use during the study, with the exception of anti-retroviral therapy
Trial locations and contacts
29 sites in 14 countries. Contact the study team or a site near you to ask about taking part.
Reference Study ID Number: WP45338 https://forpatients.roche.com/ contact
Fastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry contact
29 sites in 14 countries
United States6 sites, 6 recruiting
- Recruiting
University of Florida
Gainesville, Florida, 32610
- Recruiting
University of Kentucky Children's Hospital
Lexington, Kentucky, 40536
- Recruiting
University of Minnesota Medical Center
Minneapolis, Minnesota, 55455
- Recruiting
Virginia Commonwealth University
Richmond, Virginia, 23298-0461
- Recruiting
UC Davis
Sacramento, California, 95817
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Germany3 sites, 3 recruiting
- Recruiting
Universitätsklinikum Bonn
Bonn, 53127
- Recruiting
Gerinnungszentrum Rhein-Ruhr;Gerinnungsambulanz
Duisburg, 47051
- Recruiting
Hämophiliezentrum Med. Klinik III/Institut für Transfusionsmedizin
Frankfurt/M., 60590
Italy3 sites, 3 recruiting
- Recruiting
AOU Careggi
Florence, Tuscany, 50134
- Recruiting
IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, Lombardy, 20122
- Recruiting
Universita' Degli Studi La Sapienza-Ist.Di Ematologia
Rome, Lazio, 00161
United Kingdom3 sites, 3 recruiting
- Recruiting
St Thomas' Hospital
London, SE1 7EH
- Recruiting
Great Ormond Street Hospital
London, WC1N 3JH
- Recruiting
Manchester Royal Infirmary
Manchester, M13 9WL
Canada2 sites, 2 recruiting
- Recruiting
McGill University Health Center
Montreal, Quebec, H4A 3J1
- Recruiting
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
France2 sites, 2 recruiting
- Recruiting
Hopital Claude Huriez - CHU Lille
Lille, 59037
- Recruiting
Groupe Hospitalier Necker Enfants Malades
Paris, 75015
Japan2 sites, 2 recruiting
- Recruiting
Kurume University Hospital
Fukuoka, 830-0011
- Recruiting
Nagoya University Hospital
Nagoya, 466-8560
Spain2 sites, 2 recruiting
- Recruiting
Hospital Universitario la Paz
Madrid, 28046
- Recruiting
Hospital Universitario Virgen del Rocio
Seville, 41013
Colombia1 site, 1 recruiting
- Recruiting
IPS SURA Industriales Medellín
Medellín
Poland1 site, 1 recruiting
- Recruiting
Instytut Hematologii i Transfuzjologii
Warsaw, 02-776
South Africa1 site, 1 recruiting
- Recruiting
Charlotte Maxeke Johannesburg Academic Hospital
Johannesburg, 2193
Sweden1 site, 1 recruiting
- Recruiting
Sahlgrenska Universitetssjukhuset
Gothenburg, S-413 45
About this study
Official title: A Phase III, Multicenter, Open-Label Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Emicizumab Prophylaxis in Patients With Type 3 Von Willebrand Disease
This is a Phase III, multicenter, open-label clinical study designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab prophylaxis in participants aged 1 month and above, who have been diagnosed with Type 3 von Willebrand disease (VWD). Participants on prior standard of care (SOC) on-demand therapy will be assessed via a randomized comparison (Arm A - emicizumab prophylaxis and Arm B - continuation of SOC on-demand therapy), while participants on prior SOC prophylactic therapy (Arm C - emicizumab prophylaxis) will be assessed via intra-participant analysis with data obtained from the preceding non-interventional study (NIS), WP45335 (NCT06883240).
- Conditions
- Von Willebrand Disease, Type 3
- Being tested
- Emicizumab, von Willebrand Factor (VWF) Concentrates, Factor VIII (FVIII) Concentrates, von Willebrand Factor (VWF) and Factor VIII (FVIII) Concentrates, Bypassing Agents
- Medical subject headings
- von Willebrand Disease, Type 3
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmicizumabDrug
Also called Hemlibra, RO5534262, RG6013
Participants will receive emicizumab 3 milligrams per kilogram (mg/kg) subcutaneous (SC) injections every week (QW) for the first 4 weeks as loading doses, followed by maintenance doses of emicizumab 3 mg/kg SC once every 2 weeks (Q2W).
During the extension period, participants may remain on maintenance dose of emicizumab 3 mg/kg Q2W, or change their emicizumab maintenance regimen to 1.5 mg/kg once every week (QW) or 6 mg/kg once every 4 weeks (Q4W), if they prefer and if agreed by the investigators.
von Willebrand Factor (VWF) ConcentratesDrug
Used according to local labeling or local treatment guidelines.
Factor VIII (FVIII) ConcentratesDrug
Used according to local labeling or local treatment guidelines.
von Willebrand Factor (VWF) and Factor VIII (FVIII) ConcentratesDrug
Used according to local labeling or local treatment guidelines.
Bypassing AgentsDrug
Used according to local labeling or local treatment guidelines.
| Study group | Role | What they receive |
|---|---|---|
| Arm A (Prior On-Demand SOC): Emicizumab Prophylaxis for 24 Weeks | Experimental | Participants who are randomized to Arm A, taking on-demand standard of care (SOC) treatment at the time of study entry (and for at least 24 weeks prior to enrollment), will receive emicizumab SC prophylaxis. Receives: Drug: Emicizumab |
| Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks | Active comparator | Participants who are randomized to Arm B, taking on-demand standard of care (SOC) treatment at the time of study entry (and for at least 24 weeks prior to enrollment), will continue to receive their current SOC on-demand treatment until Week 24. Receives: Drug: von Willebrand Factor (VWF) Concentrates; Drug: Factor VIII (FVIII) Concentrates; Drug: von Willebrand Factor (VWF) and Factor VIII (FVIII) Concentrates; Drug: Bypassing Agents |
| Arm C (Prior Prophylaxis SOC): Emicizumab Prophylaxis for 24 Weeks | Experimental | Participants who enroll in Arm C, taking SOC prophylactic treatment at the time of study entry and for at least 24 weeks of observation during the preceding NIS WP45335, will receive emicizumab SC prophylaxis. Receives: Drug: Emicizumab |
| Treatment Extension Period for All Arms: Emicizumab Prophylaxis | Experimental | Participants in Arms A and C who have completed 24 weeks of emicizumab prophylaxis and who derive benefit from emicizumab will have the opportunity to continue to receive emicizumab prophylaxis in the extension period. Participants in Arm B who have completed 24 weeks of SOC on-demand treatment will have the opportunity to receive emicizumab prophylaxis in the extension period. Receives: Drug: Emicizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized Bleed Rate (ABR) for Treated Bleeds in the Randomized Arms
Measured: From Baseline to at least 24 weeks
Secondary outcomes (25)
ABR for All Bleeds in the Randomized Arms
Measured: From Baseline to at least 24 weeks
ABR for Treated Spontaneous Bleeds in the Randomized Arms
Measured: From Baseline to at least 24 weeks
ABR for Treated Joint Bleeds in the Randomized Arms
Measured: From Baseline to at least 24 weeks
Intra-Participant Comparison of the ABR for Treated Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding Non-Interventional Study (NIS) WP45335
Measured: From Baseline to at least 24 weeks
Intra-Participant Comparison of the ABR for All Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335
Measured: From Baseline to at least 24 weeks
Intra-Participant Comparison of the ABR for Treated Spontaneous Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335
Measured: From Baseline to at least 24 weeks
Intra-Participant Comparison of the ABR for Treated Joint Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335
Measured: From Baseline to at least 24 weeks
Incidence and Severity of Adverse Events, with Severity Determined According to the World Health Organization (WHO) Toxicity Grading Scale
Measured: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)
Incidence and Severity of Thromboembolic Events
Measured: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)
Incidence and Severity of Thrombotic Microangiopathy Events
Measured: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)
Incidence and Severity of Injection-Site Reactions
Measured: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)
Incidence of Adverse Events Leading to Drug Discontinuation
Measured: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)
Incidence of Severe Hypersensitivity, Anaphylaxis, or Anaphylactoid Reactions
Measured: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)
Incidence of Clinical Laboratory Abnormalities
Measured: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)
Trough Plasma Concentration of Emicizumab at Prespecified Timepoints During the Treatment Period
Measured: Predose and at prespecified timepoints from first dose of emicizumab until study completion (up to 3 years, 11 months)
Percentage of Participants with Anti-Drug Antibodies (ADAs) to Emicizumab at Baseline and with ADAs to Emicizumab During the Treatment Period
Measured: Baseline and at prespecified timepoints from first dose of emicizumab until study completion (up to 3 years, 11 months)
Change from Baseline in Respiratory Rate Over Time
Measured: Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months)
Change from Baseline in Pulse Rate Over Time
Measured: Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months)
Change from Baseline in Systolic Blood Pressure Over Time
Measured: Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months)
Change from Baseline in Diastolic Blood Pressure Over Time
Measured: Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months)
Change from Baseline in Body Temperature Over Time
Measured: Baseline, Weeks 1, 2, 25, and every 12 weeks thereafter (weeks after switch to emicizumab for Arm B only) until study completion (up to 3 years, 11 months)
Change from Baseline in Electrocardiogram (ECG) Parameters Over Time: QT, QTcF, RR, PR, and QRS Intervals
Measured: Baseline and study completion (up to 3 years, 11 months)
Change from Baseline in Heart Rate Over Time, as Measured by Electrocardiogram (ECG)
Measured: Baseline and study completion (up to 3 years, 11 months)
Change from Baseline in the PROMIS-29 Questionnaire Pain Interference Domain Score Over Time
PROMIS-29 stands for Patient-Reported Outcomes Measurement Information System-29
Measured: Baseline and at prespecified timepoints until study completion (up to 3 years, 11 months)
Change from Baseline in the PROMIS-29 Questionnaire Fatigue Domain Score Over Time
PROMIS-29 stands for Patient-Reported Outcomes Measurement Information System-29
Measured: Baseline and at prespecified timepoints until study completion (up to 3 years, 11 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2025
- Study start27 Jun 2025
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Von Willebrand Disease, Type 3Studies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants on prior SOC on-demand therapy will be randomized into Arms A and B. Participants on prior SOC prophylactic therapy, who participated in the NIS WP45335 (NCT06883240) and meet the eligibility criteria for this study, will be enrolled into Arm C.
- Masking
- None (open label)
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06998524
- Sponsor's protocol ID
- WP45338
- Other IDs
- 2024-515622-80-00
- Acronym
- WILL-EMI
- Status last verified
- Oct 2026
- First submitted
- 22 May 2025
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing