ATHN Transcends: A Natural History Study of Non-Neoplastic Hematologic Disorders

In parallel with the growth of American Thrombosis and Hemostasis Network's (ATHN) clinical studies, the number of new therapies for all congenital and acquired hematologic conditions, not just those for bleeding and clotting disorders, is increasing significantly. Some of the recently FDA-approved therapies for congenital and acquired hematologic conditions have yet to demonstrate long-term safety and effectiveness beyond the pivotal trials that led to their approval. In addition, results from well-controlled, pivotal studies often cannot be replicated once a therapy has been approved for general use.(1,2,3,4) In 2019 alone, the United States Food and Drug Administration (FDA) has issued approvals for twenty-four new therapies for congenital and acquired hematologic conditions.(5) In addition, almost 10,000 new studies for hematologic diseases are currently registered on www.clinicaltrials.gov.(6) With this increase in potential new therapies on the horizon, it is imperative that clinicians and clinical researchers in the field of non-neoplastic hematology have a uniform, secure, unbiased, and enduring method to collect long-term safety and efficacy data.

ATHN Transcends is a cohort study to determine the safety, effectiveness, and practice of therapies used in the treatment of participants with congenital or acquired non-neoplastic blood disorders and connective tissue disorders with bleeding tendency. The study consists of 7 cohorts with additional study "arms" and "modules" branching off from the cohorts.

The overarching objective of this longitudinal, observational study is to characterize the safety, effectiveness and practice of treatments for all people with congenital and acquired hematologic disorders in the US.

As emphasized in a recently published review, accurate, uniform and quality national data collection is critical in clinical research, particularly for longitudinal cohort studies covering a lifetime of biologic risk.(7)

This is a longitudinal, natural history observational cohort study being conducted at approximately 150 ATHN-affiliated sites. Participants will be followed for a minimum of 15 years. Harmonized data elements will be collected at the time of enrollment, quarterly, annually, and ad hoc. Base data will be collected for all participants. Specific data will be collected for participants enrolled in cohort-specific Arms and Modules.

Each participant will be assigned to a single cohort: Hemophilia, Von Willebrand Disease, Congenital Platelet Disorders, Rare Disorders, Bleeding Not Otherwise Specified (NOS), Thrombosis/Thrombophilia, or Non-Neoplastic Hematologic Conditions.

Study Arms and study Modules may be developed to provision disease and/or disease specific insights related to stakeholders, including but not limited to pharmaceutical companies, ATHN, and Hemophilia Treatment Centers (HTCs). Arms may branch off into product-specific data collection via Modules to be collected during the study, in conjunction with planned study assessments.

ATHN Transcends Principal Investigators

Tammuella Chrisentery-Singleton, MD Ochsner Clinic Foundation American Thrombosis and Hemostasis Network

Michael Recht, MD, PhD, MBA Yale University School of Medicine National Bleeding Disorders Foundation

PUPs Arm:

Co-Principal Investigators:

Shannon Carpenter, MD, MS University of Missouri Kansas City School of Medicine Children's Mercy Hospital

Courtney Thornburg, MD, MS University of California San Diego Rady Children's Hospital San Diego

ALTUVIIO Module:

Co-Principal Investigators Shannon Carpenter, MD, MS University of Missouri Kansas City School of Medicine Children's Mercy Hospital

Co-Principal Investigator Courtney Thornburg, MD, MS University of California San Diego Rady Children's Hospital San Diego

INHIBIT Module:

Co-Principal Investigators:

Nicoletta Machin DO, MS Assistant Professor, Division of Hematology/Oncology Hemophilia Center of Western Pennsylvania University of Pittsburgh Medical Center

Margaret V. Ragni, MD, MPH Professor of Medicine and Clinical Translational Science Department of Medicine Division of Hematology/ Oncology University of Pittsburgh Medical Center

Hemophilia Natural History Arm:

Co-Principal Investigators:

Tyler Buckner, MD, MSc Hemophilia and Thrombosis Center University of Colorado Anschutz Medical Campus

Michael Recht, MD, PhD, MBA Yale University School of Medicine National Bleeding Disorders Foundation

Rebinyn Module

Co-Principal Investigators:

Lauren Amos, MD Children's Mercy Hospital, Kansas City

Guy Young, MD University of Southern California Children's Hospital Los Angeles

Hemophilia Gene Therapy Outcomes Arm:

Co-Principal Investigators:

Janice M. Staber, MD Iowa Hemophilia and Thrombosis Center University of Iowa Stead Family Children's Hospital

Ulrike M. Reiss, MD Hemophilia Treatment Center St. Jude's Children's Research Hospital

Severe VWD Natural History Arm:

Co-Principal Investigators:

Robert F. Sidonio, Jr., MD, MSc Aflac Cancer and Blood Disorders Center, Hemophilia of Georgia Center for Bleeding and Clotting Disorders A

Angela C. Weyand, MD C.S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor

Congenital Platelet Disorders Natural History Arm:

Principal Investigator Sanjay Ahuja, MD Rainbow Babies & Children's Hospital, Case Western Reserve University

Glanzmann Thrombasthenia Module:

Co-Principal Investigators:

Divya Citla-Sridhar, MD University of Arkansas for Medical Sciences Arkansas Children's Hospital

Meera Chitlur, MD Children's Hospital of Michigan

Hemophilia Cohort

This cohort includes three Arms and five Modules:

Previously Untreated Patients (PUPs) Arm This is a pediatric focused Arm of PUPs with hemophilia A or B.

ALTUVIIIO® Module The purpose is to investigate the safety and effectiveness of ALTUVIIIO® in PUPs with hemophilia A.

INHIBIT Module This is an observational study assessing inhibitor formation in children with severe hemophilia A.

Hemophilia Natural History Arm This Arm is investigating the safety, effectiveness, and practice of treatment for people with hemophilia.

Hemlibra® Module All participants treated with Hemlibra® are eligible to participate.

Rebinyn® Module The Rebinyn® Module is a prospective study in hemophilia B participants without inhibitors.

Hemophilia Gene Therapy Outcomes Arm This Arm is investigating the safety and effectiveness of gene therapy in people with hemophilia.

HEMGENIX® Module This is an observational study to characterize the effectiveness and safety of HEMGENIX® in participants with hemophilia B.

Congenital Platelet Disorders (CPD) Natural History Arm:

The CPD Arm is investigating the safety and efficacy of hemostatic therapies in the prevention or treatment of bleeding events in adult and pediatric participants with inherited congenital platelet disorders.

Glanzmann Thrombasthenia (GT) Module:

This Module is a study of bleeding symptoms, treatments, and treatment outcomes in patients with Glanzmann thrombasthenia.

Von Willebrand Disease Cohort No arms or modules open at this time.

Rare Disorders Cohort No arms or modules open at this time.

Bleeding NOS No arms or modules open at this time.

Thrombosis/Thrombophilia No arms or modules open at this time.

Non-Neoplastic Hematologic Conditions No arms or modules open at this time.