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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
VONVENDI is administered by intravenous injection.
ADVATE is administered by intravenous injection.
Peking Union Medical College Hospital
Beijing, China
RECRUITINGNanfang Hospital Southern Medical University
Guangzhou, China
RECRUITINGJinan Central Hospital
Jihan, China
RECRUITINGRuijin Hospital Shanghai Jiaotong University School of Medicine
Shanghai, China
RECRUITINGThe First Affiliated Hospital of Soochow University
Suzhou, China
RECRUITINGInstitute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
Tianjin, China
RECRUITINGTongji Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, China
RECRUITINGNumber of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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.
Time frame: Up to 14 months
Number of Participants With TEAEs by Severity
Number of participants with severity of TEAE will be reported.
Time frame: Up to 14 months
Number of Participants With TEAEs and SAEs by Causality
Number of participants with causality related TEAEs and SAEs will be reported.
Time frame: Up to 14 months
Number of Participants With Thromboembolic Events and Severe Hypersensitivity Reactions
Number of participants with thromboembolic events and severe hypersensitivity reactions will be reported.
Time frame: Up to 14 months
Number of Participants Who Develop Neutralizing (Inhibitory) Antibodies to VWF and FVIII
Number of participants who develop neutralizing antibodies to VWF and FVIII will be reported.
Time frame: Up to 14 months
Number of Participants Who Develop Binding Antibodies to VWF and FVIII
Number of participants who develop total binding antibodies to VWF and FVIII will be reported.
Time frame: Up to 14 months
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
Number of participants with clinically significant abnormalities from baseline values in laboratory parameters per investigator assessment will be reported.
Time frame: Up to 14 months
Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG)
Number of participants with clinically significant abnormalities from baseline values in ECG per investigator assessment will be reported.
Time frame: Up to 14 months
Number of Participants With Clinically Significant Abnormalities in Vital Signs Parameters
Number of participants with clinically significant abnormalities from baseline values in vital sign parameters per investigator assessment will be reported.
Time frame: Up to 14 months
Number of Infusions of VONVENDI With or Without ADVATE per Bleeding Episode
Number of infusions of VONVENDI with or without ADVATE per bleeding episode will be reported.
Time frame: Up to 12 months
Number of Infusions of ADVATE per Bleeding Episode
Number of infusions of ADVATE per bleeding episode will be reported.
Time frame: Up to 12 months
Weight-adjusted Consumption of VONVENDI and ADVATE per Bleeding Episode
Weight-adjusted consumption of VONVENDI and ADVATE per bleeding episode will be reported.
Time frame: Up to 12 months
Time to Resolution of Bleeding Episodes
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.
Time frame: Up to 12 months
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)
AUC0-inf parameter at the baseline PK assessment will be calculated using noncompartmental analysis (NCA) for VWF:RCo, VWF:Ag, and VWF:CB.
Time frame: 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 AUC (0-inf) for VWF:RCo, VWF:Ag and VWF:CB
Dose normalized AUC0-inf parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Time frame: At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion
AUC From Time 0 to 96 Hours (AUC0-96h) for VWF:RCo, VWF:Ag and VWF:CB
AUC0-96h parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 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 AUC(0-96h) for VWF:RCo, VWF:Ag and VWF:CB
Dose normalized AUC0-96h parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Time frame: At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion
Maximum Plasma Concentration (Cmax) for VWF:RCo, VWF:Ag and VWF:CB
Cmax parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Time frame: 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 for VWF:RCo, VWF:Ag and VWF:CB
Dose normalized Cmax parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Time frame: At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion
Time to Reach Maximum Plasma Concentration (Tmax) for VWF:RCo, VWF:Ag and VWF:CB
Tmax parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Time frame: 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 for VWF:RCo, VWF:Ag and VWF:CB
Mean residence time parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Time frame: 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 for VWF:RCo, VWF:Ag and VWF:CB
Clearance parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Time frame: At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion
Terminal Half-life (T1/2) for VWF:RCo, VWF:Ag and VWF:CB
T1/2 parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Time frame: At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion
Volume of Distribution at Steady State (Vss) for VWF:RCo, VWF:Ag and VWF:CB
Vss parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo, VWF:Ag, and VWF:CB.
Time frame: At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion
Incremental Recovery (IR) at Cmax for VWF:RCo and VWF:Ag
IR parameter at the baseline PK assessment will be calculated using NCA for VWF:RCo and VWF:Ag.
Time frame: At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion
AUC From Time 0 to Last time of Measurable Activity (AUC0-tlast) for Factor VIII:Coagulation Activity (FVIII:C)
AUC0-tlast parameter at the baseline PK assessment will be calculated using NCA for FVIII: C.
Time frame: 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 for FVIII:C
Dose Normalized AUC0-tlast parameter at the baseline PK assessment will be calculated using NCA for FVIII: C.
Time frame: 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 for FVIII:C
AUC0-96h parameter at the baseline PK assessment will be calculated using NCA for FVIII: C.
Time frame: 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 for FVIII:C
Dose normalized AUC0-96h parameter at the baseline PK assessment will be calculated using NCA for FVIII: C.
Time frame: 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 for FVIII:C
Cmax parameter at the baseline PK assessment will be calculated using NCA for FVIII: C.
Time frame: 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 for FVIII:C
Dose Normalized Cmax parameter at the baseline PK assessment will be calculated using NCA for FVIII: C.
Time frame: 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 for FVIII:C
Tmax parameter at the baseline PK assessment will be calculated using NCA for FVIII: C.
Time frame: 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 Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco)
Plasma level of VONVENDI based on VWF:Rco will be reported.
Time frame: 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 Von Willebrand Factor Antigen (VWF:Ag)
Plasma level of VONVENDI based on VWF:Ag will be reported.
Time frame: 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 Von Willebrand Factor Collagen Binding (VWF:CB)
Plasma level of VONVENDI based on VWF:CB will be reported.
Time frame: 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 Factor VIII Clotting (FVIII:C)
Plasma level of FVIII:C will be reported.
Time frame: At baseline: Within 1 hour pre-infusion, 0.25, 0.50, 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours post-infusion
Total Hemostatic Efficacy Assessment 24 hours After Last Perioperative IP Infusion or at Day 14 Postoperative Visit
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.
Time frame: At 24 hours or Day 14
Total Volume of Actual and Predicted Intraoperative Blood Loss After the Surgery as Assessed by the Operating Surgeon
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.
Time frame: From Intraoperative through completion of surgery (up to Day 14)
Intraoperative Hemostatic Efficacy Score as Assessed by Operating Surgeon at Completion of Surgery
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.
Time frame: At completion of surgery (up to Day 14)
Daily Intra- and Postoperative Weight-adjusted Dose of VONVENDI With or Without ADVATE Through Postoperative Day 14
Daily intra- and postoperative weight-adjusted dose of VONVENDI with or without ADVATE through postoperative day 14 will be reported.
Time frame: From day of surgery through postoperative Day 14