ATHN 9: Severe VWD Natural History Study

Von Willebrand Diseases Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03853486
• Other study ID #: ATHN 9
• Status: Active, not recruiting
• Start date: March 18, 2019
• Est. completion date: January 31, 2025

Study information

• Verified date: January 2024
• Source: American Thrombosis and Hemostasis Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 108
• Est. completion date: January 31, 2025
• Est. primary completion date: December 31, 2024
• Gender: All
• Age group: N/A and older

Eligibility

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).

Related Conditions & MeSH terms

• Von Willebrand Diseases

Locations

Country	Name	City	State
United States	University of Michigan Hemophilia and Coagulation Disorders	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta/Emory	Atlanta	Georgia
United States	University of Colorado Denver Hemophilia and Thrombosis Center	Aurora	Colorado
United States	Nationwide Children's Hospital Columbus	Columbus	Ohio
United States	Children's Hospital of Michigan Hemostasis and Thrombosis Center	Detroit	Michigan
United States	Michigan State University Center for Bleeding and Clotting Disorders	East Lansing	Michigan
United States	Connecticut Bleeding and Clotting Disorders Center	Farmington	Connecticut
United States	University of Florida Hemophilia Treatment Center	Gainesville	Florida
United States	Hemophilia Outreach Center	Green Bay	Wisconsin
United States	Indiana Hemophilia and Thrombosis Center (IHTC)	Indianapolis	Indiana
United States	University of Tennessee, University Clinical Health (Memphis)	Memphis	Tennessee
United States	Versiti - Blood Center of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Louisiana Center for Bleeding and Clotting Disorders	New Orleans	Louisiana
United States	Center for Inherited Blood Disorders	Orange	California
United States	Bleeding and Clotting Disorders Institute	Peoria	Illinois
United States	Pennsylvania Comprehensive Hemophilia and Thrombophilia Program / Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Hemophilia Center of Western Pennsylvania	Pittsburgh	Pennsylvania
United States	Oregon Health	Portland	Oregon
United States	Rhode Island Hemostasis & Thrombosis Center	Providence	Rhode Island
United States	Mayo Comprehensive Hemophilia Center	Rochester	Minnesota
United States	Washington University Center for Treatment of Bleeding and Blood Clotting Disorders	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
American Thrombosis and Hemostasis Network	Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Factor replacement used as prophylaxis.	Report number of particpants using factor replacement as prophylaxis.	3 years
Secondary	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
Secondary	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
Secondary	Calculate the effectiveness of VWD treatment as measured by health care utilization.	The number of visits/hospitalizations.	3 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Calculate the success of VWD treatment as measured by health care utilization.	The types of visits/hospitalizations	3 years
Secondary	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