ATHN 9: Severe VWD Natural History Study

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: 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.

• Study Type: Observational
• Enrollment (Actual): 108

Contacts and Locations

• Study Contact: Name: Haduwa Momoh; Phone Number: 1-800-360-2846; Email: hmomoh@athn.org
• Study Contact Backup: Name: Jessica Callis; Email: jcallis@athn.org

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Center for Inherited Blood Disorders
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver Hemophilia and Thrombosis Center
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • Connecticut Bleeding and Clotting Disorders Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Hemophilia Treatment Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta/Emory
  • Illinois
    • Peoria, Illinois, United States, 61615
      • Bleeding and Clotting Disorders Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Indiana Hemophilia and Thrombosis Center (IHTC)
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana Center for Bleeding and Clotting Disorders
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hemophilia and Coagulation Disorders
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan Hemostasis and Thrombosis Center
    • East Lansing, Michigan, United States, 48823
      • Michigan State University Center for Bleeding and Clotting Disorders
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Comprehensive Hemophilia Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University Center for Treatment of Bleeding and Blood Clotting Disorders
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital Columbus
  • Oregon
    • Portland, Oregon, United States, 91239
      • Oregon Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Pennsylvania Comprehensive Hemophilia and Thrombophilia Program / Hospital of the University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Hemophilia Center of Western Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hemostasis & Thrombosis Center
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • University of Tennessee, University Clinical Health (Memphis)
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54311
      • Hemophilia Outreach Center
    • Milwaukee, Wisconsin, United States, 53201
      • Versiti - Blood Center of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• 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.

Description

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).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: American Thrombosis and Hemostasis Network
• Collaborators: Takeda
• Investigators: Principal Investigator: Robert Sidonio, MD, Emory University / Children's Healthcare of Atlanta; Principal Investigator: Angela Weyand, MD, University of Michigan Hemophilia and Coagulation Disorders

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2019
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: January 11, 2019
• First Submitted That Met QC Criteria: February 22, 2019
• First Posted (Actual): February 25, 2019

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: von Willebrand Disease; VWD; Factor; VWF; ATHN 9
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Blood Platelet Disorders; Von Willebrand Diseases
• Other Study ID Numbers: ATHN 9

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No