A Study of Recombinant Von Willebrand Factor (rVWF) (TAK-577) in Children With Severe Von Willebrand Disease (vWD)
- Conditions
- Von Willebrand Disease (VWD)
- Interventions
- Biological: Recombinant von Willebrand Factor (rVWF)Biological: ADVATE
- Registration Number
- NCT05582993
- Lead Sponsor
- Takeda
- Brief Summary
The main aim of the study is to evaluate the effectiveness of prophylaxis with recombinant von Willebrand factor (rVWF) in children. This study will enroll those participants who have been previously treated with VWF product or with a plasma-derived VWF (pdVWF) product. In this study, participants will be treated with rVWF for 12 months.
During the study, participants will visit the study clinic 6 times after treatment initiation.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 24
Not provided
- The participant has been diagnosed with pseudo VWD or another hereditary or acquired coagulation disorder other than VWD (example, qualitative and quantitative platelet disorders or elevated prothrombin time/international normalized ratio 1.4).
- The participant has a history or presence of a VWF inhibitor at screening.
- The participant has a history or presence of an factor VIII (FVIII) inhibitor with a titer >=0.4 Bethesda units (BU) (by the Nijmegen-modified Bethesda assay) or >=0.6 BU (by the 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 <200 per cubic millimeter or microliter (/mm^3).
- The participant has been diagnosed with significant liver disease per the investigator's medical assessment of the participant's current condition or medical history or as evidenced by, but not limited to, any of the following: serum alanine aminotransferase (ALT) greater than 5 times the upper limit of normal (ULN), hypoalbuminemia, portal vein hypertension (example, presence of otherwise unexplained splenomegaly, history of esophageal varices), or liver cirrhosis classified as Child-Pugh class B or C.
- The participant has been diagnosed with renal disease, with a serum creatinine level >=2.5 milligram per deciliter (mg/dL).
- The participant has a platelet count <100,000 per milliliter (/mL) at screening (because participants with type 2B VWD are considered eligible for this study, for participants with type 2B VWD, platelet count[s] at screening will be evaluated in consultation with the sponsor, taking into consideration historical trends in platelet counts and the investigator's medical assessment of the participants condition).
- The participant has been treated with an immunomodulatory drug, excluding topical treatment (example, 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 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 not received OD or prophylactic treatment with a VWF product prior to this study.
- The participant has a progressive fatal disease and/or life expectancy of less than 15 months.
- The participant is already scheduled for a surgical intervention that will have to be performed while the participant is participating in the study.
- The participant is unable to complete screening procedures and/or comply with the requirements of the protocol in the opinion of the investigator, based on the joint prescreening evaluation held between the investigator and the sponsor.
- 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 (that is, children, partner/spouse, siblings, and parents) as well as employees.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 3: Participants With Age <6 years ADVATE Participants with age \<6 years who have received OD therapy of VWF product or prophylactic treatment with a pdVWF product will receive rVWF with an initial dose selected within the range of 40 to 60 IU/kg rVWF, intravenous infusions, twice-weekly for 12 months. Participants may receive rVWF with or without ADVATE intravenous infusions, when indicated (as deemed necessary for breakthrough bleeding episode treatment and perioperative bleeding management). Cohort 2: Participants With Age >=6 to <12 years ADVATE Participants with age \>=6 to \<12 years who have received OD therapy of VWF product or prophylactic treatment with a pdVWF product will receive rVWF with an initial dose selected within the range of 40 to 60 IU/kg rVWF, intravenous infusions, twice-weekly for 12 months. Participants may receive rVWF with or without ADVATE intravenous infusions, when indicated (as deemed necessary for breakthrough bleeding episode treatment and perioperative bleeding management). Cohort 2: Participants With Age >=6 to <12 years Recombinant von Willebrand Factor (rVWF) Participants with age \>=6 to \<12 years who have received OD therapy of VWF product or prophylactic treatment with a pdVWF product will receive rVWF with an initial dose selected within the range of 40 to 60 IU/kg rVWF, intravenous infusions, twice-weekly for 12 months. Participants may receive rVWF with or without ADVATE intravenous infusions, when indicated (as deemed necessary for breakthrough bleeding episode treatment and perioperative bleeding management). Cohort 1: Participants With Age >=12 to <18 years Recombinant von Willebrand Factor (rVWF) Participants with age greater than or equal to (\>=) 12 to less than (\<) 18 years who have received on-demand (OD) therapy or prophylactic treatment with a pdVWF product will receive rVWF with an initial dose selected within the range of 40 to 60 international units per kilogram (IU/kg) rVWF, intravenous infusions, twice-weekly for 12 months. Participants may receive rVWF with or without ADVATE intravenous infusions, when indicated (as deemed necessary for breakthrough bleeding episode treatment and perioperative bleeding management). Cohort 1: Participants With Age >=12 to <18 years ADVATE Participants with age greater than or equal to (\>=) 12 to less than (\<) 18 years who have received on-demand (OD) therapy or prophylactic treatment with a pdVWF product will receive rVWF with an initial dose selected within the range of 40 to 60 international units per kilogram (IU/kg) rVWF, intravenous infusions, twice-weekly for 12 months. Participants may receive rVWF with or without ADVATE intravenous infusions, when indicated (as deemed necessary for breakthrough bleeding episode treatment and perioperative bleeding management). Cohort 3: Participants With Age <6 years Recombinant von Willebrand Factor (rVWF) Participants with age \<6 years who have received OD therapy of VWF product or prophylactic treatment with a pdVWF product will receive rVWF with an initial dose selected within the range of 40 to 60 IU/kg rVWF, intravenous infusions, twice-weekly for 12 months. Participants may receive rVWF with or without ADVATE intravenous infusions, when indicated (as deemed necessary for breakthrough bleeding episode treatment and perioperative bleeding management).
- Primary Outcome Measures
Name Time Method Annualized Bleeding Rate (ABR) for Spontaneous or Traumatic Bleeding Episodes as Assessed by Investigator During Prophylactic Treatment With rVWF 12 months ABR during the study compared to historical ABR for each participant for both spontaneous and traumatic bleeding episodes as classified by the investigator during prophylactic treatment with rVWF will be reported.
- Secondary Outcome Measures
Name Time Method Number of Participants With TEAEs and SAEs by Causality 12 months Number of participants with causality related TEAEs and SAEs will be reported.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) 12 months Number of participants with TEAEs and SAEs will be reported.
Number of Participants Who Develop Neutralizing Antibodies to VWF and Factor VIII (FVIII) 12 months Number of participants who develop neutralizing antibodies to VWF and FVIII will be reported.
Number of Participants Who Develop Binding Antibodies to Chinese hamster ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG), and Recombinant Furin (rFurin) 12 months CHO, mouse IgG, and rFurin are proteins that may be potentially present in trace amount in final drug product. Number of participants who develop binding antibodies to CHO proteins, mouse IgG, and rFurin will be reported.
Number of Participants With Clinically Significant Change From Baseline Values in Vital Sign Parameters 12 months Number of participants with clinically significant change from baseline values in vital sign parameters per investigator assessment will be reported.
Plasma Level of rVWF based on Von Willebrand Factor Collagen Binding (VWF:CB) Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion Plasma level of rVWF based on VWF:CB will be reported.
Number of Participants With Thromboembolic Events, Hypersensitivity Reactions and Infusion-Related Reactions (IRR) 12 months Number of participants with thromboembolic events, hypersensitivity reactions and IRR will be reported.
Number of Participants With Clinically Significant Change From Baseline Values in Laboratory Parameters 12 months Number of participants with clinically significant change from baseline values in laboratory parameters per investigator assessment will be reported.
Number of Spontaneous ABR During Prophylactic Treatment With rVWF by Location of Bleeding 12 months Number of spontaneous ABR during prophylactic treatment with rVWF by location of bleeding will be reported.
Total Weight Adjusted Consumption of rVWF Per Month During Prophylactic Treatment 12 months Total weight adjusted consumption of rVWF per month during prophylactic treatment will be reported.
Weight-adjusted Consumption of rVWF and ADVATE per Bleeding Episode 12 months Weight-adjusted consumption of rVWF and ADVATE per bleeding episode will be reported.
Number of Participants With TEAEs by Severity 12 months Number of participants with severity of TEAE will be reported.
Number of Participants Who Develop Total Binding Antibodies to VWF and FVIII 12 months Number of participants who develop total binding antibodies to VWF and FVIII will be reported.
Number of Participants Previously Receiving On-demand Treatment who will Achieve ABR Percent Reduction Success 12 months ABR percent reduction success is defined as at least 25% reduction of ABR during rVWF prophylaxis relative to the participant's own historical ABR during OD treatment prior to enrollment in this study. Number of participants previously receiving on-demand treatment who will achieve ABR percent reduction success will be reported.
ABR for Bleeding Episodes by Bleeding Cause Historically and While on Prophylactic Treatment With rVWF 12 months ABR for bleeding episodes by bleeding cause historically and while on prophylactic treatment with rVWF will be reported.
Overall Hemostatic Efficacy Rating of Breakthrough Bleed Treatment at Resolution of the Bleeding Episode 12 months Overall hemostatic efficacy rating of breakthrough bleed treatment at resolution of the bleeding episode will be reported.
Plasma Level of rVWF based on Von Willebrand Factor Glycoprotein 1b Binding (VWF:GP1bM) Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion Plasma level of rVWF based on VWF:GP1bM will be reported.
Incremental Recovery Based on VWF:Ag 12 months Incremental recovery based on VWF:Ag will be reported.
Maximum Plasma Level During the Partial Dosing Interval at Steady State (Cmax;ss) for VWF:Rco Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion Cmax;ss for VWF:Rco will be reported.
Minimum Time to Reach the Maximum Plasma Level at Steady State (Tmax;ss) for VWF:Rco Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion Tmax;ss for VWF:Rco will be reported.
Volume of Distribution at Steady State (Vss) for VWF:Rco Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion Vss for VWF:Rco will be reported.
Area Under the Level Versus Time Curve From 0 to 96 Hours (AUC0-96; ss) for FVIII:C Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion AUC0-96; ss for FVIII:C will be reported.
Number of Participants With Categorized ABR 12 months ABR categorized as 0, 0-2, 2-5, or \>5 bleeding episodes during rVWF prophylaxis. Number of participants with categorized ABR will be reported.
Number of pdVWF Switch Participants With Spontaneous ABR Preservation Success 12 months ABR preservation success defined as achieving an ABR for spontaneous bleeding episodes during rVWF prophylaxis that is no greater than the participant's own historical ABR during prophylactic treatment with pdVWF prior to enrollment in this study. Number of pdVWF switch participants with spontaneous ABR preservation success will be reported.
ABR for Bleeding Episodes Spontaneous, or Traumatic by Treatment Given Historically and While on Prophylactic Treatment With rVWF 12 months ABR for bleeding episodes spontaneous, or traumatic by treatment given historically and while on prophylactic treatment with rVWF will be reported.
Incremental Recovery Based on VWF:GP1bM 12 months Incremental recovery based on VWF:GP1bM will be reported.
Ratio of Area Under the Plasma Level Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) and Area Under the Level Versus Time Curve From 0 to 96 Hours (AUC0-96; ss) for VWF:Rco for FVIII:C Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion Ratio of AUC0- Tau;ss and AUC0-96; ss for FVIII:C will be reported.
Total Number of Infusions Administered Per Week During Prophylactic Treatment With rVWF 12 months Total number of infusions administered per week during prophylactic treatment with rVWF will be reported.
Average Number of Infusions Per Week During Prophylactic Treatment With rVWF 12 months Average number of infusions per week during prophylactic treatment with rVWF will be reported.
Number of Infusions of rVWF and ADVATE (rFVIII, octocog alfa) per Bleeding Episode 12 months Number of infusions of rVWF and ADVATE per bleeding episode will be reported.
Plasma Level of rVWF based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion Plasma level of rVWF based on VWF:Rco will be reported.
Plasma Level of rVWF based on Von Willebrand Factor Antigen (VWF:Ag) Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion Plasma level of rVWF based on VWF:Ag will be reported.
Incremental Recovery Based on VWF:CB 12 months Incremental recovery based on VWF:CB will be reported.
Ratio of Area Under the Plasma Level Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) and Area Under the Level Versus Time Curve From 0 to 96 Hours (AUC0-96; ss) for VWF:Rco Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion Ratio of AUC0- Tau;ss/AUC0-96; ss for VWF:Rco will be reported.
Maximum Plasma Level During the Partial Dosing Interval at Steady State (Cmax;ss) for FVIII:C Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion Cmax;ss for FVIII:C will be reported.
Plasma Level of Factor VIII Clotting (FVIII:C) Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion Plasma level of FVIII:C will be reported.
Incremental Recovery Based on VWF:Rco 12 months Incremental recovery based on VWF:Rco will be reported.
Terminal Half-life (T1/2) for VWF:Rco Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion TT1/2 based on VWF:Rco will be reported.
Clearance (CL) for VWF:Rco Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion CL for VWF:Rco will be reported.
Minimum Time to Reach the Maximum Plasma Level at Steady State (Tmax;ss) for FVIII:C Within 30 minutes pre-infusion and at multiple timepoints (up to 96 hours) post-infusion Tmax;ss for FVIII:C will be reported.
Trial Locations
- Locations (4)
Children's Health Care d/b/a Children's Minnesota
🇺🇸Minneapolis, Minnesota, United States
Hemostase Clinique - Institut Coeur-Poumons
🇫🇷Lille, France
Hopital Edouard Herriot - CHU Lyon
🇫🇷Lyon, France
Azienda Ospedaliera Pediatrica Santobono Pausillipon
🇮🇹Napoli, Italy