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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All Participants With VWD | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VONVENDI | Biological | VONVENDI is administered by intravenous injection. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number 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. | Up to 14 months |
| Number of Participants With TEAEs by Severity | Number of participants with severity of TEAE will be reported. | 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. | 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. | 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. | Up to 14 months |
| Number of Participants Who Develop Binding Antibodies to VWF and FVIII |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 12 months |
| Number of Infusions of ADVATE per Bleeding Episode |
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Inclusion Criteria
Participant must voluntarily sign an institutional review board (IRB)/independent ethics committee-approved written informed consent form after all relevant aspects of the study have been explained and discussed with the participant.
Participant has a documented diagnosis of severe VWD (baseline VWF:RCo less than [<]20 international units [IU]deciliter [dL]) with a diagnosis of VWD type verified per the following recommended criteria:
Participant is at least 18 years of age at screening.
Participant is ethnic Chinese and lives in China, including those from Taiwan, Hong Kong, and Macao.
If female of childbearing potential, participant presents with a negative pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
Participant is willing and able to comply with the requirements of the protocol.
Participant has had a minimum of 3 documented bleeds that indicated the need for VWF coagulation factor replacement therapies during the previous 12 months prior to enrollment.
Exclusion Criteria
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Takeda Contact | Contact | +1-877-825-3327 | medinfoUS@takeda.com |
| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking Union Medical College Hospital | Recruiting | Beijing | 100006 | China |
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| Label | URL |
|---|---|
| Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed. | View source |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
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| ID | Term |
|---|---|
| D014842 | von Willebrand Diseases |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D005169 | Factor VIII |
| C078147 | F8 protein, human |
| ID | Term |
|---|---|
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
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| ADVATE | Biological | ADVATE is administered by intravenous injection. |
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Number of participants who develop total binding antibodies to VWF and FVIII will be reported.
| 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. | 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. | 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. | Up to 14 months |
Number of infusions of ADVATE per bleeding episode will be reported.
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | From day of surgery through postoperative Day 14 |
| Nanfang Hospital Southern Medical University | Recruiting | Guangzhou | 510515 | China |
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| Jinan Central Hospital | Recruiting | Jihan | 250013 | China |
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| Ruijin Hospital Shanghai Jiaotong University School of Medicine | Recruiting | Shanghai | 201801 | China |
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| The First Affiliated Hospital of Soochow University | Recruiting | Suzhou | 215005 | China |
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| Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences | Recruiting | Tianjin | 300052 | China |
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| Tongji Hospital Tongji Medical College Huazhong University of Science and Technology | Recruiting | Wuhan | 430032 | China |
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| D020147 | Coagulation Protein Disorders |
| D001791 | Blood Platelet Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D011498 |
| Protein Precursors |
| D001685 | Biological Factors |