Clinical trial NCT06998524: A Study to Assess the Efficacy and Safety of Emicizumab in Participants With Type 3 Von Willebrand Disease
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Von Willebrand Disease, Type 3
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2025-05-31
Enrollment: 66
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Annualized Bleed Rate (ABR) for Treated Bleeds in the Randomized Arms
timeFrame: From Baseline to at least 24 weeks
Secondary outcomes:
measure: ABR for All Bleeds in the Randomized Arms
timeFrame: From Baseline to at least 24 weeks
measure: ABR for Treated Spontaneous Bleeds in the Randomized Arms
timeFrame: From Baseline to at least 24 weeks
measure: ABR for Treated Joint Bleeds in the Randomized Arms
timeFrame: From Baseline to at least 24 weeks
measure: Intra-Participant Comparison of the ABR for Treated Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding Non-Interventional Study (NIS) WP45335
timeFrame: From Baseline to at least 24 weeks
measure: Intra-Participant Comparison of the ABR for All Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335
timeFrame: From Baseline to at least 24 weeks
measure: Intra-Participant Comparison of the ABR for Treated Spontaneous Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335
timeFrame: From Baseline to at least 24 weeks
measure: Intra-Participant Comparison of the ABR for Treated Joint Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335
timeFrame: From Baseline to at least 24 weeks
measure: Incidence and Severity of Adverse Events, with Severity Determined According to the World Health Organization (WHO) Toxicity Grading Scale
timeFrame: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)
measure: Incidence and Severity of Thromboembolic Events
timeFrame: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)
measure: Incidence and Severity of Thrombotic Microangiopathy Events
timeFrame: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)
measure: Incidence and Severity of Injection-Site Reactions
timeFrame: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)
measure: Incidence of Adverse Events Leading to Drug Discontinuation
timeFrame: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)
measure: Incidence of Severe Hypersensitivity, Anaphylaxis, or Anaphylactoid Reactions
timeFrame: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)
measure: Incidence of Clinical Laboratory Abnormalities
timeFrame: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)
measure: Trough Plasma Concentration of Emicizumab at Prespecified Timepoints During the Treatment Period
timeFrame: Predose and at prespecified timepoints from first dose of emicizumab until study completion (up to 3 years, 11 months)
measure: Percentage of Participants with Anti-Drug Antibodies (ADAs) to Emicizumab at Baseline and with ADAs to Emicizumab During the Treatment Period
timeFrame: Baseline and at prespecified timepoints from first dose of emicizumab until study completion (up to 3 years, 11 months)
measure: Change from Baseline in Respiratory Rate Over Time
timeFrame: 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)
measure: Change from Baseline in Pulse Rate Over Time
timeFrame: 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)
measure: Change from Baseline in Systolic Blood Pressure Over Time
timeFrame: 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)
measure: Change from Baseline in Diastolic Blood Pressure Over Time
timeFrame: 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)
measure: Change from Baseline in Body Temperature Over Time
timeFrame: 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)
measure: Change from Baseline in Electrocardiogram (ECG) Parameters Over Time: QT, QTcF, RR, PR, and QRS Intervals
timeFrame: Baseline and study completion (up to 3 years, 11 months)
measure: Change from Baseline in Heart Rate Over Time, as Measured by Electrocardiogram (ECG)
timeFrame: Baseline and study completion (up to 3 years, 11 months)
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: