ATHN 9: Severe VWD Natural History Study

Study Overview
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Brief Summary
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ATHN 9 is a natural history study to assess the safety of various Von Willebrand Factor (VWF) regimens for different indications (on-demand, surgery and prophylaxis) in adult and pediatric participants with clinically severe congenital VWD.

Detailed Description
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The overarching objective of this longitudinal, observational and prospective study is to characterize the safety and effectiveness of factor replacement in participants with clinically severe congenital VWD (VWF:Ag, VWF:GPlbM or VWF:RCo of ≤30% or ≤40% of normal with severe bleeding phenotype defined as requiring recurrent use of factor concentrates) enrolled in the ATHNdataset. This is a longitudinal, observational cohort study being conducted at up to 30 ATHN-affiliated sites. Participants will be followed for 2 years from time of study enrolment. The total study duration is 3 years. Safety will be measured by the number of reported events defined by the European Haemophilia Safety Surveillance (EUHASS) program. In addition, although not specifically defined by EUHASS, treatment-emergent side effects of therapy will be included as reportable events including: hypersensitivity/allergic reactions, thrombotic events, VW Factor inhibitor development, treatment-emergent side effects of therapy, transfusion-transmitted infections, malignancy, cardiovascular events, neurological events, unexpected poor efficacy and death. Secondary objectives of ATHN 9 are: to enrich and analyze the data from currently enrolled participants with clinically severe congenital VWD in the ATHNdataset via the collection of laboratory data consisting of a standardized diagnostic battery using an ELISA based VWF activity assay, and genetic sequence analysis of VWF coding regions and adjacent non-coding regions; to establish a platform for sub-studies for participants with congenital severe VWD, that are treated with VWF products on demand or have started on or switched to a particular VWF containing product for prophylaxis; to evaluate the use of factor replacement as prophylaxis in participants over 6-month time periods; to describe bleeding events, changes in overall bleeding and annualized bleeding rate (ABR) over the course of the study as measured by individual bleeding components; and to describe real-world effectiveness of VWD treatment as measured by health care utilization and quality of life.

Official Title
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ATHN 9: A Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment for People With Severe Von Willebrand Disease (VWD)

Conditions
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Von Willebrand Diseases

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with severe Von Willebrand Disease with Type 3 VWD or VWF:RCo, VWF:GPlbM or VWF:Ag ≤30% of pooled normal control plasma on more than one occasion; Participants with clinically severe VWD as defined by VWF:RCo, VWF:GPlbM or VWF:Ag ≤40% of normal with severe bleeding phenotype defined as requiring recurrent use of factor concentrates; and Co-enrollment in the ATHNdataset. Exclusion Criteria: Diagnosis of platelet-type VWD; Diagnosis of acquired VWD (clinical diagnosis based on association with hypothyroidism, lymphoproliferative and myeloproliferative disorders, malignancies and cardiovascular disease, typically aortic stenosis or LVAD).
Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reported adverse events from VWF regimens for different indications (on-demand, surgery, and prophylaxis) as measured by EUHASS. | Number of adverse events as measured by EUHASS as well as treatment-emergent side effects of therapy for various Von Willebrand Factor (VWF) regimens for different indications (on-demand, surgery and prophylaxis) in adult and pediatric participants with clinically severe congenital VWD. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Enrich and analyze data collected about AE events as defined by EUHASS using standardized diagnostic battery using an ELISA-based VWF assay. | To enrich and analyze the data from currently enrolled participants with clinically severe congenital VWD in the ATHNdataset via the collection of laboratory data consisting of a standardized diagnostic battery using an ELISA-based VWF assay. | 3 years | 
| Enrich and analyze data collected about AE events, as defined by EUHASS using genetic sequence analysis of VWF coding regions and adjacent non-coding regions. | To enrich and analyze the data from currently enrolled participants with clinically-severe congenital VWD in the ATHNdataset via the collection of laboratory data using genetic sequence analysis of VWF coding regions and adjacent non-coding regions. | 2 years | 
| Substudy modules will be developed to evaluate and report on cohorts of study participants who initiate treatment with specific product. | To measure the number of participants taking unique VWF products. | 2 years | 
| Factor replacement used as prophylaxis. | Report number of particpants using factor replacement as prophylaxis. | 3 years | 
| Capture bleeding events using the Pictorial Bleeding. Assessment Chart. | The number of participants with bleeding events analyzed over the course of the study. | 3 years | 
| Capture annualized bleeding rate (ABR) using ISTH BAT Assessment Tool. | The change in the annualized bleeding rate (ABR) for participants over the course of the study by analyzing the number of bleeding events divided by the length of time of the treatment (in years). | 3 years | 
| Calculate the effectiveness of VWD treatment as measured by health care utilization. | The number of visits/hospitalizations. | 3 years | 
| Analyze the effectivness of VWD treatment as measured by score on PROMIS questionnaire using the 7 PROMIS domains (depression; anxiety; physical function; pain; fatigue; sleep disturbance; and participation in social roles and activities). | Health-related Quality of Life measured annually by the Patient Reported Outcomes Measurement Information System (PROMIS ®) Profile. | 3 years | 
| Capture bleeding events using the Pictorial Bleeding Assessment Chart. | The number of participants with bleeding events analyzed over the course of the study. | 3 years | 
| Capture annualized bleeding rates (ABR) using the Pictorial Bleeding Assessment Chart. | The change in the annualized bleeding rate (ABR) for participants over the course of the study by analyzing the number of bleeding events divided by the length of time of the treatment (in years). | 3 years | 
| Calculate the success of VWD treatment as measured by health care utilization. | The types of visits/hospitalizations | 3 years | 
| Capture the effectiveness of VWD treatments using health-related quality of life. | Measure walking ability as part of quality of life using the V-WIQ questionnaire. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VWF, von Willebrand Disease, VWD, Factor, ATHN 9