A Study of Recombinant Von Willebrand Factor (rVWF) in Pediatric and Adult Participants With Severe Von Willebrand Disease (VWD)
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| ClinicalTrials.gov Identifier: NCT03879135 |
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Recruitment Status :
Recruiting
First Posted : March 18, 2019
Last Update Posted : April 21, 2022
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Sponsor:
Baxalta now part of Shire
Collaborator:
Takeda Development Center Americas, Inc.
Information provided by (Responsible Party):
Takeda ( Baxalta now part of Shire )
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Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Von Willebrand Disease (VWD) | Biological: rVWF Biological: rFVIII | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 71 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Prevention |
| Official Title: | A Phase 3b, Prospective, Open-Label, Uncontrolled, Multicenter Study on Long-Term Safety and Efficacy of rVWF in Pediatric and Adult Subjects With Severe Von Willebrand Disease (VWD) |
| Actual Study Start Date : | April 1, 2019 |
| Estimated Primary Completion Date : | December 31, 2023 |
| Estimated Study Completion Date : | December 31, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Von Willebrand disease
| Arm | Intervention/treatment |
|---|---|
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Experimental: On-Demand
Participants will receive recombinant von Willebrand factor (rVWF) (with or without ADVATE).
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Biological: rVWF
Recombinant von Willebrand factor
Other Names:
Biological: rFVIII Recombinant Factor VIII
Other Names:
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Experimental: Prophylaxis
Participants will receive recombinant von Willebrand factor (rVWF).
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Biological: rVWF
Recombinant von Willebrand factor
Other Names:
Biological: rFVIII Recombinant Factor VIII
Other Names:
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Primary Outcome Measures :
- Spontaneous Annualized Bleeding Rate (ABR) [ Time Frame: First 12 months of treatment ]Spontaneous ABR during prophylaxis treatment with rVWF (vonicog alfa)
Secondary Outcome Measures :
- Adverse Events (AEs)/Serious Adverse Events (SAEs) [ Time Frame: Throughout the study participation period, up to 3 years ]AEs/ SAEs: incidence, severity, causality
- Thromboembolic Events [ Time Frame: Throughout the study participation period, up to 3 years ]Occurrence of thromboembolic events
- Hypersensitivity Reactions [ Time Frame: Throughout the study participation period, up to 3 years ]Occurrence of hypersensitivity reactions
- Number of Participants who Develop Neutralizing Antibodies to von Willebrand factor (VWF) [ Time Frame: Throughout the study participation period, up to 3 years ]Number of participants who develop neutralizing antibodies (inhibitors) to VWF
- Number of Participants who Develop Neutralizing Antibodies to Factor VIII (FVIII) [ Time Frame: Throughout the study participation period, up to 3 years ]Number of participants who develop neutralizing antibodies (inhibitors) to FVIII
- Number of Participants who Develop Total Binding Antibodies to von Willebrand factor (VWF) [ Time Frame: Throughout the study participation period, up to 3 years ]Number of participants who develop total binding antibodies to VWF
- Number of Participants who Develop Total Binding Antibodies to Factor VIII (FVIII) [ Time Frame: Throughout the study participation period, up to 3 years ]Number of participants who develop total binding antibodies to FVIII
- Number of Participants who Develop Binding Antibodies to Chinese hamster ovary (CHO) proteins [ Time Frame: Throughout the study participation period, up to 3 years ]Number of participants who develop binding antibodies to CHO proteins
- Number of Participants who Develop Binding Antibodies to Mouse Immunoglobulin G (IgG) [ Time Frame: Throughout the study participation period, up to 3 years ]Number of participants who develop binding antibodies to mouse IgG
- Number of Participants who Develop Binding Antibodies to recombinant Furin (rFurin) [ Time Frame: Throughout the study participation period, up to 3 years ]Number of participants who develop binding antibodies to rFurin
- Number of Participants With Clinically Significant Changes in Vital Signs [ Time Frame: Throughout the study participation period, up to 3 years ]Clinically significant changes in vital signs (body temperature, blood pressure, respiration and pulse) will be assessed from baseline up to 3 years
- Number of Participants With Clinically Significant Changes in Laboratory Parameters [ Time Frame: Throughout the study participation period, up to 3 years ]Clinically significant changes in laboratory parameters (clinical chemistry, fasting lipid panel and determination of fat-soluble vitamins, bile acids and other cholestasis biochemical markers) will be assessed from baseline up to 3 years
- Spontaneous Annualized Bleeding Rate (ABR) Under Prophylactic Treatment [ Time Frame: Throughout the study participation period, up to 3 years ]Spontaneous ABR under prophylactic treatment with rVWF (vonicog alfa) while enrolled in the study
- Categorized Weekly Number of Infusions [ Time Frame: Throughout the study participation period, up to 3 years ]Categorized as 1, 2 or >=3 during prophylactic treatment with rVWF (vonicog alfa)
- Categorized Spontaneous Annualized Bleeding Rate (ABR) [ Time Frame: Throughout the study participation period, up to 3 years ]Categorized as 0, 1-2, 3-5, or >5 bleeding episodes during rVWF (vonicog alfa) prophylaxis
- Time to First Bleeding Event [ Time Frame: Throughout the study participation period, up to 3 years ]Under each prophylaxis regimen
- Spontaneous Annualized Bleeding Rate (ABR) by Location of Bleeding [ Time Frame: Throughout the study participation period, up to 3 years ]Gastrointestinal [GI], epistaxis, joint bleeding, menorrhagia, oral, muscle and soft tissue, etc. while on prophylactic treatment with rVWF (vonicog alfa)
- Total Number of Infusions [ Time Frame: Throughout the study participation period, up to 3 years ]Total number of infusions during prophylactic treatment with rVWF (vonicog alfa)
- Average Number of Infusions [ Time Frame: Throughout the study participation period, up to 3 years ]Per week during prophylactic treatment with rVWF (vonicog alfa)
- Total Weight Adjusted Consumption of recombinant von Willebrand factor (rVWF) (vonicog alfa) [ Time Frame: Throughout the study participation period, up to 3 years ]During prophylactic treatment
- Number of Participants who Achieve Transfusion-free Maintenance of Hemoglobin Levels [ Time Frame: Throughout the study participation period, up to 3 years ]Transfusion free maintenance of hemoglobin levels over time
- Ferritin Levels Over Time [ Time Frame: Throughout the study participation period, up to 3 years ]Ferritin levels over time will be reported.
- Overall Hemostatic Efficacy Rating [ Time Frame: Initial 12 months of study ]At the resolution of bleed with respect to the treatment of bleeding episodes for the initial 12 months of study
- Number of Infusions [ Time Frame: Throughout the study participation period, up to 3 years ]Number of infusions of rVWF (vonicog alfa) and ADVATE (rFVIII, octocog alfa) utilized to treat bleeding episodes while enrolled in the study
- Weight-adjusted Consumption [ Time Frame: Throughout the study participation period, up to 3 years ]Weight-adjusted consumption of rVWF (vonicog alfa) and ADVATE (rFVIII, octocog alfa) per bleeding episode while enrolled in the study
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| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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) <20 International Units per deciliter [IU/dL]) with a history of requiring substitution therapy with von Willebrand factor (vWF) concentrate to control bleeding:
- Type 1 (VWF:RCo <20 IU/dL) or,
- Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by genotype), Type 2M or,
- Type 3 (Von Willebrand factor antigen (VWF:Ag) less than or equal to (<=) 3 IU/dL).
Diagnosis is confirmed by genetic testing and multimer analysis, documented in participant history or at screening.
- Participant has been receiving OD therapy with VWF products for at least 12 months, and prophylactic treatment is recommended by the investigator.
- Participant has greater than or equal to (>=) 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 <40 kilogram per meter square (kg/m^2).
Exclusion Criteria:
The participant will be excluded from the study if any of the following exclusion criteria are met.
- The participant has been diagnosed with Type 2N VWD, pseudo VWD, or another hereditary or acquired coagulation disorder other than VWD (eg, qualitative and quantitative platelet disorders or elevated prothrombin time (PT)/international normalized ratio [INR] >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 <200/cubic millimeters (mm^3).
- The participant has been diagnosed with significant liver disease per 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; hypoalbuminemia; portal vein hypertension (eg, 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 (CR) level >=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 recovered. For all other participants, end of study (EOS) visit for 071102 or 071301 will be completed per protocol and the completed EOS in Study 071102 or 071301 will also serve as the screening visit for this continuation study (SHP677-304).
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03879135
Contacts
| Contact: Shire Contact | +1 866 842 5335 | ClinicalTransparency@takeda.com |
Locations
Show 33 study locations
Sponsors and Collaborators
Baxalta now part of Shire
Takeda Development Center Americas, Inc.
Investigators
| Study Director: | Study Director | Takeda |
Additional Information:
| Responsible Party: | Baxalta now part of Shire |
| ClinicalTrials.gov Identifier: | NCT03879135 |
| Other Study ID Numbers: |
SHP677-304 2018-003453-16 ( EudraCT Number ) |
| First Posted: | March 18, 2019 Key Record Dates |
| Last Update Posted: | April 21, 2022 |
| Last Verified: | April 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | 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. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) |
| Access Criteria: | 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. |
| URL: | https://vivli.org/ourmember/takeda/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Von Willebrand Diseases Blood Coagulation Disorders, Inherited Blood Coagulation Disorders Hematologic Diseases Coagulation Protein Disorders |
Blood Platelet Disorders Hemorrhagic Disorders Genetic Diseases, Inborn Factor VIII Coagulants |