Phase 3
N=35
A Study of Recombinant Von Willebrand Factor (rVWF) in Pediatric and Adult Participants With Severe Von Willebrand Disease (VWD)
Von Willebrand Disease (VWD)
Bottom Line
View on ClinicalTrials.gov: NCT03879135 ↗Enrolled (actual)
35
Serious AEs
22.9%
Results posted
Sep 2025
Primary outcome: Primary: Spontaneous Annualized Bleeding Rate (sABR) — 1.430; 1.040; 0.000; 3.022 spontaneous bleeds per year
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- rVWF (Biological); rFVIII (Biological)
- Age
- Pediatric, Adult, Older Adult · 0+ yrs
- Sex
- All
- Sponsor
- Baxalta now part of Shire
- Primary completion
- Jan 2025
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Spontaneous Annualized Bleeding Rate (sABR) |
1.430; 1.040; 0.000; 3.022 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs |
8; 1; 1; 4; 15; 2 | — |
| SECONDARY Number of Participants Based on Severity of TEAEs |
7; 1; 1; 4; 14; 2 | — |
| SECONDARY Number of Participants Based on Causality of TEAEs |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Thromboembolic Events |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Hypersensitivity Reactions |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (VWF) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants Who Developed Neutralizing Antibodies to Factor VIII (FVIII) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants Who Developed Total Binding Antibodies to Von Willebrand Factor (VWF) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants Who Developed Total Binding Antibodies to Factor VIII (FVIII) |
0; 0; 0; 0; 1; 0 | — |
| SECONDARY Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants Who Developed Binding Antibodies to Mouse Immunoglobulin G (IgG) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants Who Develop Binding Antibodies to Recombinant Furin (rFurin) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Changes in Vital Signs |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Changes in Laboratory Parameters |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Spontaneous Annualized Bleeding Rate (sABR) Under Prophylactic Treatment |
1.122; 0.330; 0.000; 2.110 | — |
| SECONDARY Number of Participants Categorized Based on Weekly Number of Infusions |
1; 0; 0; 0; 6; 1 | — |
| SECONDARY Number of Participants Categorized Based on Spontaneous Annualized Bleeding Rate (sABR) |
5; 0; 1; 0; 3; 1 | — |
| SECONDARY Time to First Bleeding Event on Prophylaxis Treatment |
172; 141; NA; 88 | — |
| SECONDARY Spontaneous Annualized Bleeding Rate (sABR) by Location of Bleeding |
0.033; 0.000; 0.000; 0.000; 0.000; 0.000 | — |
| SECONDARY Total Number of Infusions During Prophylactic Treatment |
287.8; 157.0; 177.0; 159.2 | — |
| SECONDARY Average Number of Infusions Per Week During Prophylactic Treatment |
1.87; 1.01; 1.14; 1.38 | — |
| SECONDARY Total Weight Adjusted Consumption of Recombinant Von Willebrand Factor (rVWF) (Vonicog Alfa) Per Participant During Prophylactic Treatment |
14953.497; 9992.460; 9270.620; 9171.746 | — |
| SECONDARY Number of Participants Who Achieved Transfusion-free Maintenance of Hemoglobin Levels |
8; 1; 1; 5 | — |
| SECONDARY Change From Baseline in Ferritin Levels Over Time |
148.5; 90.8; 11.0; -31.0; 0.0; -43.8 | — |
| SECONDARY Overall Hemostatic Efficacy Rating |
74; 21; 1; 0; 0; 0 | — |
| SECONDARY Number of Infusions of Vonicog Alfa |
1.1; 1.2 | — |
| SECONDARY Number of Infusions of ADVATE |
1.1; 1.0 | — |
| SECONDARY Weight-adjusted Consumption of Vonicog Alfa Per Bleeding Episode |
56.109; 61.713 | — |
| SECONDARY Weight-adjusted Consumption of ADVATE Per Bleeding Episode |
39.217; 35.175 | — |
Summary
The main aim of the study is to check effectiveness of rVWF (vonicog alfa) prophylaxis based on the annualized bleeding rate (ABR) of spontaneous (not related to trauma) bleeding episodes in pediatric and adult participants during the first 12 months on study treatment.
The participants will be treated with rVWF for a maximum of 3 years. Their von Willebrand Disease will be treated according to Investigational product (IP) dosing directions.
Eligibility Criteria
Inclusion Criteria
The participant will not be considered eligible for the study without meeting all of the criteria below.
Participants who have completed Study 071301 or Study 071102 (or participants who have completed the surgery arm treatment in Study 071102 and want to continue to receive on-demand (OD) treatment) and are willing to immediately transition into this study, must meet the following 2 criteria to be eligible for this study:
- If female of childbearing potential, has a negative blood/urine pregnancy test at screening and agrees to employ highly effective birth control measures for the duration of the study.
- Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol.
New participants (Cohort 4) who meet the above 2 and ALL the following additional criteria are eligible for this study:
- Participant has a documented diagnosis of severe von Willebrand disease (VWD) (baseline von Willebrand factor: Ristocetin cofactor (VWF:RCo) =) 3 documented spontaneous bleeds (not including menorrhagia) requiring VWF treatment during the past 12 months.
- Participant has available records that reliably evaluate type, frequency, and treatment of bleeding episodes for at least 12 months preceding enrollment; up to 24 months of retrospective data should be collected if available.
- Participant is >=12 years old at the time of screening and has a body mass index >=15 but 1.4).
- The participant has a history or presence of a VWF inhibitor at screening.
- The participant has a history or presence of a Factor VIII (FVIII) inhibitor with a titer >=0.4 Bethesda units (BU) (by Nijmegen modified Bethesda assay) or >=0.6 BU (by Bethesda assay).
- The participant has a known hypersensitivity to any of the components of the study drugs, such as mouse or hamster proteins.
- The participant has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies, or animal allergies.
- The participant has a medical history of a thromboembolic event.
- The participant is human immunodeficiency virus (HIV) positive with an absolute Helper T cell (CD4) count =2.5 milligrams per deciliter (mg/dL).
- The participant has a platelet count <100,000/milliliter (mL) at screening.
- The participant has been treated with an immunomodulatory drug, excluding topical treatment (eg, ointments, nasal sprays), within 30 days prior to signing the informed consent (or assent, if appropriate).
- The participant is pregnant or lactating at the time of enrollment.
- The participant has cervical or uterine conditions causing menorrhagia or metrorrhagia (including infection, dysplasia).
- The participant has participated in another clinical study involving another investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
- The participant has a progressive fatal disease and/or life expectancy of less than 15 months.
- For new OD participants, the participant is scheduled for a surgical intervention.
- The participant is identified by the investigator as being unable or unwilling to cooperate with study procedures.
- The participant has a mental condition rendering him/her unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.
- The participant is member of the study team or in a dependent relationship with one of the study team members which includes close relatives (i.e., children, partner/spouse, siblings and parents) as well as employees.
Delay criteria Only for Cohort 4, if the participant presents with an acute bleeding episodes or acute illness (eg, influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, and non-seasonal asthma) the screening visit will be postponed until the participant has recove
Data sourced from ClinicalTrials.gov (NCT03879135). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.