A Study to Assess the Efficacy and Safety of Emicizumab in Participants With Type 3 Von Willebrand Disease

Phase 3

Recruiting

• Conditions: Von Willebrand Disease, Type 3
• Interventions: Drug: Emicizumab; Drug: von Willebrand Factor (VWF) Concentrates; Drug: Factor VIII (FVIII) Concentrates; Drug: von Willebrand Factor (VWF) and Factor VIII (FVIII) Concentrates; Drug: Bypassing Agents

• Registration Number: NCT06998524
• Lead Sponsor: Hoffmann-La Roche

Brief 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 2 years 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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-05-22
• Study First Submitted QC: 2025-05-22
• Study First Posted: 2025-05-31
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-09
• Last Update Posted: 2025-06-12
• Study Start: 2025-06-15
• Primary Completion: 2027-12-15
• Study Completion: 2029-05-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

• 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:

• 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:

• 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (Prior On-Demand SOC): Emicizumab Prophylaxis for 24 Weeks	Emicizumab	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.
Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks	von Willebrand Factor (VWF) Concentrates	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.
Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks	Factor VIII (FVIII) Concentrates	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.
Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks	von Willebrand Factor (VWF) and Factor VIII (FVIII) Concentrates	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.
Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks	Bypassing Agents	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.
Arm C (Prior Prophylaxis SOC): Emicizumab Prophylaxis for 24 Weeks	Emicizumab	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.
Treatment Extension Period for All Arms: Emicizumab Prophylaxis	Emicizumab	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.

Primary Outcome Measures

Name	Time	Method
Annualized Bleed Rate (ABR) for Treated Bleeds in the Randomized Arms	From Baseline to at least 24 weeks

Secondary Outcome Measures

Name	Time	Method
Change from Baseline in Pulse Rate Over Time	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	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	Baseline and study completion (up to 3 years, 11 months)
Change from Baseline in Heart Rate Over Time, as Measured by Electrocardiogram (ECG)	Baseline and study completion (up to 3 years, 11 months)
ABR for All Bleeds in the Randomized Arms	From Baseline to at least 24 weeks
ABR for Treated Spontaneous Bleeds in the Randomized Arms	From Baseline to at least 24 weeks
ABR for Treated Joint Bleeds in the Randomized Arms	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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)

Trial Locations

Locations (1)

UZ Leuven Gasthuisberg; 🇧🇪 Leuven, Belgium