Clinical trial NCT03853486: ATHN 9: Severe VWD Natural History Study
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)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Von Willebrand Diseases
Keywords: VWF
von Willebrand Disease
VWD
Factor
ATHN 9
Lead sponsor: American Thrombosis and Hemostasis Network
Sponsor class: NETWORK
Collaborators: name: Takeda
First posted: 2019-02-25
Enrollment: 108
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility 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).

Primary outcomes:
measure: Reported adverse events from VWF regimens for different indications (on-demand, surgery, and prophylaxis) as measured by EUHASS.
timeFrame: 2 years
Secondary outcomes:
measure: Enrich and analyze data collected about AE events as defined by EUHASS using standardized diagnostic battery using an ELISA-based VWF assay.
timeFrame: 3 years
measure: 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.
timeFrame: 2 years
measure: Substudy modules will be developed to evaluate and report on cohorts of study participants who initiate treatment with specific product.
timeFrame: 2 years
measure: Factor replacement used as prophylaxis.
timeFrame: 3 years
measure: Capture bleeding events using the Pictorial Bleeding. Assessment Chart.
timeFrame: 3 years
measure: Capture annualized bleeding rate (ABR) using ISTH BAT Assessment Tool.
timeFrame: 3 years
measure: Calculate the effectiveness of VWD treatment as measured by health care utilization.
timeFrame: 3 years
measure: 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).
timeFrame: 3 years
measure: Capture bleeding events using the Pictorial Bleeding Assessment Chart.
timeFrame: 3 years
measure: Capture annualized bleeding rates (ABR) using the Pictorial Bleeding Assessment Chart.
timeFrame: 3 years
measure: Calculate the success of VWD treatment as measured by health care utilization.
timeFrame: 3 years
measure: Capture the effectiveness of VWD treatments using health-related quality of life.
timeFrame: 3 years
Other outcomes:
Locations:
city: Orange
country: United States
facility: Center for Inherited Blood Disorders
state: California
city: Aurora
country: United States
facility: University of Colorado Denver Hemophilia and Thrombosis Center
state: Colorado
city: Farmington
country: United States
facility: Connecticut Bleeding and Clotting Disorders Center
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida Hemophilia Treatment Center
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta/Emory
state: Georgia
city: Peoria
country: United States
facility: Bleeding and Clotting Disorders Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center (IHTC)
state: Indiana
city: New Orleans
country: United States
facility: Louisiana Center for Bleeding and Clotting Disorders
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan Hemophilia and Coagulation Disorders
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan Hemostasis and Thrombosis Center
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University Center for Bleeding and Clotting Disorders
state: Michigan
city: Rochester
country: United States
facility: Mayo Comprehensive Hemophilia Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University Center for Treatment of Bleeding and Blood Clotting Disorders
state: Missouri
city: Columbus
country: United States
facility: Nationwide Children's Hospital Columbus
state: Ohio
city: Portland
country: United States
facility: Oregon Health
state: Oregon
city: Philadelphia
country: United States
facility: Pennsylvania Comprehensive Hemophilia and Thrombophilia Program / Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Hemophilia Center of Western Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hemostasis & Thrombosis Center
state: Rhode Island
city: Memphis
country: United States
facility: University of Tennessee, University Clinical Health (Memphis)
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Green Bay
country: United States
facility: Hemophilia Outreach Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Versiti - Blood Center of Wisconsin
state: Wisconsin
Study officials:
affiliation: Emory University / Children's Healthcare of Atlanta
name: Robert Sidonio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan Hemophilia and Coagulation Disorders
name: Angela Weyand, MD
role: PRINCIPAL_INVESTIGATOR
References: