A Study of Recombinant Von Willebrand Factor (rVWF) in Chinese Participants With Von Willebrand Disease (vWD)
- Conditions
- Von Willebrand Disease (VWD)
- Interventions
- Registration Number
- NCT07129343
- Lead Sponsor
- Takeda
- Brief Summary
The main aim of this study is to find out if VONVENDI is safe for adult Chinese participants with VWD. The study will also check how well VONVENDI helps control bleeding with or without product ADVATE in the participants who may need elective surgery or dental procedures. In addition, the study will also examine how VONVENDI is processed by the body (known as pharmacokinetic \[PK\]) and how the drug helps the body respond or improve a condition (pharmacodynamic \[PD\]).
Participants will receive an initial dose of VONVENDI of 40 to 80 international units per kilogram (IU/kg) of body weight. If a participant's baseline factor VIII (FVIII) level is not high enough to help stop bleeding, VONVENDI will be given along with 30 to 45 IU/kg of ADVATE rFVIII.
Participants will be in the study for approximately 14 months. During the study, participants will be followed up at clinics or over telephone calls.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description All Participants With VWD VONVENDI Participants will receive a single intravenous (IV) dose of VONVENDI at baseline PK assessment. During the 12-month on-demand (OD) treatment period, any bleeding episodes requiring replacement therapy with VWF will be treated with VONVENDI with or without ADVATE. Participants may also receive VONVENDI with or without ADVATE intravenous infusions, when indicated deemed necessary for perioperative bleeding management \[major, minor and oral surgery\]. Participants will receive initial dose of VONVENDI of 40 to 80 IU/kg of body weight. All Participants With VWD ADVATE Participants will receive a single intravenous (IV) dose of VONVENDI at baseline PK assessment. During the 12-month on-demand (OD) treatment period, any bleeding episodes requiring replacement therapy with VWF will be treated with VONVENDI with or without ADVATE. Participants may also receive VONVENDI with or without ADVATE intravenous infusions, when indicated deemed necessary for perioperative bleeding management \[major, minor and oral surgery\]. Participants will receive initial dose of VONVENDI of 40 to 80 IU/kg of body weight.
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Up to 14 months A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. An SAE is any untoward medical occurrence that at any dose: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event in the opinion of the healthcare provider, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. TEAEs consist of both serious and non-serious adverse events.
Number of Participants With TEAEs by Severity Up to 14 months Number of participants with severity of TEAE will be reported.
Number of Participants Who Develop Binding Antibodies to VWF and FVIII Up to 14 months Number of participants who develop total binding antibodies to VWF and FVIII will be reported.
Number of Participants With TEAEs and SAEs by Causality Up to 14 months Number of participants with causality related TEAEs and SAEs will be reported.
Number of Participants With Thromboembolic Events and Severe Hypersensitivity Reactions Up to 14 months Number of participants with thromboembolic events and severe hypersensitivity reactions will be reported.
Number of Participants Who Develop Neutralizing (Inhibitory) Antibodies to VWF and FVIII Up to 14 months Number of participants who develop neutralizing antibodies to VWF and FVIII will be reported.
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters Up to 14 months Number of participants with clinically significant abnormalities from baseline values in laboratory parameters per investigator assessment will be reported.
Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Up to 14 months Number of participants with clinically significant abnormalities from baseline values in ECG per investigator assessment will be reported.
Number of Participants With Clinically Significant Abnormalities in Vital Signs Parameters Up to 14 months Number of participants with clinically significant abnormalities from baseline values in vital sign parameters per investigator assessment will be reported.
- Secondary Outcome Measures
Name Time Method Weight-adjusted Consumption of VONVENDI and ADVATE per Bleeding Episode Up to 12 months Weight-adjusted consumption of VONVENDI and ADVATE per bleeding episode will be reported.
Time to Resolution of Bleeding Episodes Up to 12 months Time to resolution of the bleeding episodes will be calculated as the difference between the date/time of the first IP infusion for the bleeding episode to the date/time of the bleeding episode resolution.
Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-inf) for VWF: Ristocetin Cofactor (VWF:Rco), VWF: Antigen (VWF:Ag) and VWF: Collagen Binding Capacity (VWF:CB) At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion AUC0-inf parameter at the baseline PK assessment will be calculated using noncompartmental analysis (NCA) for VWF:RCo, VWF:Ag, and VWF:CB.
Dose Normalized AUC (0-inf) for VWF:RCo, VWF:Ag and VWF:CB At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Dose normalized AUC0-inf parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Number of Infusions of VONVENDI With or Without ADVATE per Bleeding Episode Up to 12 months Number of infusions of VONVENDI with or without ADVATE per bleeding episode will be reported.
Number of Infusions of ADVATE per Bleeding Episode Up to 12 months Number of infusions of ADVATE per bleeding episode will be reported.
AUC From Time 0 to 96 Hours (AUC0-96h) for VWF:RCo, VWF:Ag and VWF:CB At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion AUC0-96h parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Dose Normalized AUC(0-96h) for VWF:RCo, VWF:Ag and VWF:CB At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Dose normalized AUC0-96h parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Maximum Plasma Concentration (Cmax) for VWF:RCo, VWF:Ag and VWF:CB At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Cmax parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Dose Normalized Cmax for VWF:RCo, VWF:Ag and VWF:CB At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Dose normalized Cmax parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Time to Reach Maximum Plasma Concentration (Tmax) for VWF:RCo, VWF:Ag and VWF:CB At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Tmax parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Mean Residence Time for VWF:RCo, VWF:Ag and VWF:CB At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Mean residence time parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Clearance for VWF:RCo, VWF:Ag and VWF:CB At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Clearance parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Terminal Half-life (T1/2) for VWF:RCo, VWF:Ag and VWF:CB At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion T1/2 parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Volume of Distribution at Steady State (Vss) for VWF:RCo, VWF:Ag and VWF:CB At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Vss parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Incremental Recovery (IR) at Cmax for VWF:RCo and VWF:Ag At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion IR parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo and VWF:Ag.
AUC From Time 0 to Last time of Measurable Activity (AUC0-tlast) for Factor VIII:Coagulation Activity (FVIII:C) At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion AUC0-tlast parameter at the baseline PK assessment will be calculated using NCA for FVIII: C.
Dose Normalized AUC0-tlast for FVIII:C At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Dose Normalized AUC0-tlast parameter at the baseline PK assessment will be calculated using NCA for FVIII: C.
AUC0-96h for FVIII:C At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion AUC0-96h parameter at the baseline PK assessment will be calculated using NCA for FVIII: C.
Dose Normalized AUC0-96h for FVIII:C At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Dose normalized AUC0-96h parameter at the baseline PK assessment will be calculated using NCA for FVIII: C.
Cmax for FVIII:C At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Cmax parameter at the baseline PK assessment will be calculated using NCA for FVIII: C.
Dose Normalized Cmax for FVIII:C At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Dose Normalized Cmax parameter at the baseline PK assessment will be calculated using NCA for FVIII: C.
Tmax for FVIII:C At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Tmax parameter at the baseline PK assessment will be calculated using NCA for FVIII: C.
Plasma Level of VONVENDI based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Plasma level of VONVENDI based on VWF:Rco will be reported.
Plasma Level of VONVENDI based on Von Willebrand Factor Antigen (VWF:Ag) At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Plasma level of VONVENDI based on VWF:Ag will be reported.
Plasma Level of VONVENDI based on Von Willebrand Factor Collagen Binding (VWF:CB) At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Plasma level of VONVENDI based on VWF:CB will be reported.
Total Volume of Actual and Predicted Intraoperative Blood Loss After the Surgery as Assessed by the Operating Surgeon From Intraoperative through completion of surgery (up to Day 14) Intraoperative actual blood loss will be assessed by the operating surgeon at the completion of surgery using a predefined 4-point rating scale. 1- Excellent (intraoperative blood loss was less than or equal to the maximum expected for the type of procedure performed in a hemostatically normal individual \[\<=\]100 percent \[%\]); 2- Good (intraoperative blood loss up to 50% more than the maximum expected blood loss for the type of procedure performed in a hemostatically normal individual \[101%-150%\]); 3- Moderate (intraoperative blood loss exceeding 50% of the expected for the type of procedure performed in a hemostatically normal individual \[greater than (\>)150%\]); 4- None (uncontrolled hemorrhage due to an inadequate therapeutic response despite appropriate dosing, necessitating a change of clotting factor replacement regimen). Lower scores indicate better hemostatic efficacy. Scoring is calculated by comparing the actual blood loss versus predicted blood loss.
Intraoperative Hemostatic Efficacy Score as Assessed by Operating Surgeon at Completion of Surgery At completion of surgery (up to Day 14) The hemostasis assessment rating scale ranges from 1 to 4, where 1 = Excellent, 2 = Good, 3 = Moderate, and 4 = None. Lower scores indicate better hemostatic efficacy.
Daily Intra- and Postoperative Weight-adjusted Dose of VONVENDI With or Without ADVATE Through Postoperative Day 14 From day of surgery through postoperative Day 14 Daily intra- and postoperative weight-adjusted dose of VONVENDI with or without ADVATE through postoperative day 14 will be reported.
Plasma Level of Factor VIII Clotting (FVIII:C) At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion Plasma level of FVIII:C will be reported.
Total Hemostatic Efficacy Assessment 24 hours After Last Perioperative IP Infusion or at Day 14 Postoperative Visit At 24 hours or Day 14 The overall hemostatic efficacy of VONVENDI, with or without ADVATE, will be assessed by the investigator using the hemostatic efficacy assessment rating scale either 24 hours after the last perioperative infusion or at the Day 14 postoperative visit, whichever comes first.