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ATHN 9: Severe VWD Natural History Study

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ClinicalTrials.gov Identifier: NCT03853486
Recruitment Status : Enrolling by invitation
First Posted : February 25, 2019
Last Update Posted : April 18, 2019
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
American Thrombosis and Hemostasis Network

Brief Summary:
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.

Condition or disease
Von Willebrand Diseases

Detailed Description:

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.

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Study Type : Observational
Estimated Enrollment : 130 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: ATHN 9: A Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment for People With Severe Von Willebrand Disease (VWD)
Actual Study Start Date : March 18, 2019
Estimated Primary Completion Date : January 31, 2021
Estimated Study Completion Date : January 31, 2022

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Reported adverse events from VWF regimens for different indications (on-demand, surgery, and prophylaxis) as measured by EUHASS. [ Time Frame: 2 years ]
    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.


Secondary Outcome Measures :
  1. Enrich and analyze data collected about AE events as defined by EUHASS using standardized diagnostic battery using an ELISA-based VWF assay. [ Time Frame: 3 years ]
    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.

  2. 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. [ Time Frame: 2 years ]
    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.

  3. Substudy modules will be developed to evaluate and report on cohorts of study participants who initiate treatment with specific product. [ Time Frame: 2 years ]
    To measure the number of participants taking unique VWF products.

  4. Factor replacement used as prophylaxis. [ Time Frame: 3 years ]
    Report number of particpants using factor replacement as prophylaxis.

  5. Capture bleeding events using the Pictorial Bleeding. Assessment Chart. [ Time Frame: 3 years ]
    The number of participants with bleeding events analyzed over the course of the study.

  6. Capture annualized bleeding rate (ABR) using ISTH BAT Assessment Tool. [ Time Frame: 3 years ]
    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).

  7. Calculate the effectiveness of VWD treatment as measured by health care utilization. [ Time Frame: 3 years ]
    The number of visits/hospitalizations.

  8. 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). [ Time Frame: 3 years ]
    Health-related Quality of Life measured annually by the Patient Reported Outcomes Measurement Information System (PROMIS ®) Profile.

  9. Capture bleeding events using the Pictorial Bleeding Assessment Chart. [ Time Frame: 3 years ]
    The number of participants with bleeding events analyzed over the course of the study.

  10. Capture annualized bleeding rates (ABR) using the Pictorial Bleeding Assessment Chart. [ Time Frame: 3 years ]
    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).

  11. Calculate the success of VWD treatment as measured by health care utilization. [ Time Frame: 3 years ]
    The types of visits/hospitalizations

  12. Capture the effectiveness of VWD treatments using health-related quality of life. [ Time Frame: 3 years ]
    Measure walking ability as part of quality of life using the V-WIQ questionnaire.


Biospecimen Retention:   Samples With DNA

All participants will undergo laboratory evaluation. The remaining specimen volume will be stored and may be used for future research.

Specimens will be tested as follows:

  • FVIII Activity, VWF Antigen, and the VWF:GPIbM Activity Assay. Reflex testing may include: VWD Type 2B Binding, VWD Type 2N Binding, VWF Propeptide Antigen, and/or VWF Quantitative Multimers
  • Genetic sequence analysis of VWF coding regions and adjacent non-coding regions


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
This is a natural history study in which it is anticipated that approximately 130 participants will be enrolled. The study will attempt to enroll a target number of at least 30 participants who are receiving VONVENDI but will not mandate the use of VONVENDI.
Criteria

Inclusion Criteria:

  1. 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;
  2. 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
  3. Co-enrollment in the ATHNdataset.

Exclusion Criteria:

  1. Diagnosis of platelet-type VWD;
  2. Diagnosis of acquired VWD (clinical diagnosis based on association with hypothyroidism, lymphoproliferative and myeloproliferative disorders, malignancies and cardiovascular disease, typically aortic stenosis or LVAD).

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): NCT03853486


  Show 27 Study Locations
Sponsors and Collaborators
American Thrombosis and Hemostasis Network
Takeda
Investigators
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Principal Investigator: Robert Sidonio, MD Emory University / Children's Healthcare of Atlanta
Principal Investigator: Angela Weyand, MD University of Michigan Hemophilia and Coagulation Disorders

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Responsible Party: American Thrombosis and Hemostasis Network
ClinicalTrials.gov Identifier: NCT03853486     History of Changes
Other Study ID Numbers: ATHN 9
First Posted: February 25, 2019    Key Record Dates
Last Update Posted: April 18, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by American Thrombosis and Hemostasis Network:
VWF
von Willebrand Disease
VWD
Factor
ATHN 9

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