A Study to Assess the Efficacy and Safety of Emicizumab in Participants With Type 3 Von Willebrand Disease (WILL-EMI)

Roche

Status and phase: Enrolling; Phase 3

Conditions: Von Willebrand Disease, Type 3

Treatments: Drug: von Willebrand Factor (VWF) Concentrates; Drug: von Willebrand Factor (VWF) and Factor VIII (FVIII) Concentrates; Drug: Bypassing Agents; Drug: Factor VIII (FVIII) Concentrates; Drug: Emicizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06998524

WP45338

2024-515622-80-00 (Registry Identifier)

Details and patient eligibility

About

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).

Enrollment: 75 estimated patients

Sex: All

Ages: 1+ month old

Volunteers: No Healthy Volunteers

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:

• Age ≥1 month at the time of signing Informed Consent/Assent Form
• 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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

75 participants in 4 patient groups

Arm A (Prior On-Demand SOC): Emicizumab Prophylaxis for 24 Weeks

Experimental group

Description:

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.

Treatment:

Drug: Emicizumab

Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks

Active Comparator group

Description:

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.

Treatment:

Drug: Factor VIII (FVIII) Concentrates

Drug: Bypassing Agents

Drug: von Willebrand Factor (VWF) and Factor VIII (FVIII) Concentrates

Drug: von Willebrand Factor (VWF) Concentrates

Arm C (Prior Prophylaxis SOC): Emicizumab Prophylaxis for 24 Weeks

Experimental group

Description:

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:

Drug: Emicizumab

Treatment Extension Period for All Arms: Emicizumab Prophylaxis

Experimental group

Description:

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.

Treatment:

Drug: Emicizumab