Von Willebrand Disease, Type 3
Conditions
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 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).
Interventions
DRUGEmicizumab
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.
DRUGvon Willebrand Factor (VWF) Concentrates
Used according to local labeling or local treatment guidelines.
DRUGFactor VIII (FVIII) Concentrates
Used according to local labeling or local treatment guidelines.
DRUGvon Willebrand Factor (VWF) and Factor VIII (FVIII) Concentrates
Used according to local labeling or local treatment guidelines.
DRUGBypassing Agents
Used according to local labeling or local treatment guidelines.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
1 Months to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Annualized Bleed Rate (ABR) for Treated Bleeds in the Randomized Arms | From Baseline to at least 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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) | — |
| 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) | — |
| Change from Baseline in the PROMIS-29 Questionnaire Pain Interference Domain Score Over Time | Baseline and at prespecified timepoints until study completion (up to 3 years, 11 months) | PROMIS-29 stands for Patient-Reported Outcomes Measurement Information System-29 |
| Change from Baseline in the PROMIS-29 Questionnaire Fatigue Domain Score Over Time | Baseline and at prespecified timepoints until study completion (up to 3 years, 11 months) | PROMIS-29 stands for Patient-Reported Outcomes Measurement Information System-29 |
| 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) | — |
| 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 | — |
| 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) | — |
| 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 | — |
Countries
Belgium, Canada, Colombia, France, Germany, Italy, Japan, Netherlands, Poland, South Africa, Spain, Sweden, United Kingdom, United States
Contacts
CONTACTReference Study ID Number: WP45338 https://forpatients.roche.com/
CONTACTFastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed