Sickle Cell Disease Clinical Trial
Official title:
ATHN Transcends: A Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment in People With 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)
Status | Recruiting |
Enrollment | 3000 |
Est. completion date | December 2035 |
Est. primary completion date | June 2035 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A and older |
Eligibility | Participants who meet the following inclusion criteria and none of the exclusion criteria are eligible for enrollment in the base study: Inclusion Criteria: 1. Any age 2. Having a congenital or acquired non-neoplastic hematologic disorder; or 3. Having a bleeding phenotype as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score with an unknown diagnosis; or 4. Connective tissue disorder with bleeding tendency as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score. Exclusion Criteria: 1. Does not qualify for inclusion in a cohort 2. Unable to give informed consent or assent 3. Unwilling to perform study procedures Cohort Participant Selection Each participant is to be enrolled in the cohort for which they qualify as defined below. Hemophilia Cohort Inclusion Criteria: Participants who meet any of the following inclusion criteria are eligible for enrollment into this cohort: 1. Factor VIII or factor IX activity < 50%, without another explanation for low clotting factor other than congenital hemophilia or being a known carrier for congenital hemophilia; OR 2. Being a known carrier for congenital hemophilia with a factor VIII or factor IX activity greater than or equal to 50% with or without a bleeding phenotype as indicated by an age-adjusted abnormal ISTH Bleeding Assessment Tool score; OR 3. Known congenital hemophilia that have a factor level >50% after receiving vector; OR 4. Acquired hemophilia Exclusion Criteria: None Von Willebrand Disease Cohort Inclusion Criteria: Participants who meet the following inclusion criteria are eligible for enrollment into this cohort: 1. Meeting the definition of VWD or low VWF per most recent international guidelines Exclusion Criteria: None Congenital Platelet Disorders Cohort Inclusion Criteria: Participants who meet the following inclusion criteria are eligible for enrollment into this cohort: 1. Abnormalities of platelet function 1. Glanzmann thrombasthenia (GPIIb or GPIIIa) 2. Bernard-Soulier syndrome (GPIbalpha, GPIbbeta, or GPIX) 2. Abnormalities of platelet granules 3. Abnormalities of platelet signal transduction 4. Abnormalities of platelet secretion 5. Collagen Receptor Defect 6. ADP Receptor Defect 7. Thromboxane Receptor Defect 8. Giant Platelet Disorder 9. Abnormalities in platelet aggregation testing due to another or unknown cause (not drug related) Exclusion Criteria: Platelet disorders secondary to medications or other substances Rare Disorders Cohort Inclusion Criteria: Participants who meet the following inclusion criteria are eligible for enrollment into this cohort: 1. Have an established Rare Coagulation Disorder (RCD) diagnosis of one of the following: 1. PAI-1 deficiency 2. Factor I, II, V, VII, X, XI, XIII deficiencies 3. Combined FV and FVIII deficiency 4. Plasminogen deficiency 5. Decreased tissue plasminogen activator 6. Afibrinogenemia/hypofibrinogenemia/dysfibrinogenemia Exclusion Criteria: None Bleeding NOS Cohort Inclusion Criteria: Participants who meet the following inclusion criteria are eligible for enrollment into this cohort: 1. Have a bleeding phenotype as indicated by an age-adjusted abnormal ISTH Bleeding Assessment Tool score with an unknown diagnosis; OR 2. Connective tissue disorder with bleeding tendency as indicated by an age-adjusted abnormal ISTH Bleeding Assessment Tool score Exclusion Criteria: None Thrombosis/Thrombophilia Cohort Inclusion Criteria Participants who meet the following inclusion criteria are eligible for enrollment into this cohort: 1. Have a prior history of arterial or venous thrombosis 2. Patients with a known congenital or acquired thrombophilia with or without a thrombosis a. Common congenital thrombophilias:: i. Protein C deficiency ii. Protein S deficiency iii. Antithrombin deficiency iv. Factor V Leiden v. Prothrombin gene mutation b. Rare genetic factors i. Hyperhomocysteinemia c. Indeterminate genetic factors i. Elevated factor VIII ii. Elevated factor IX iii. Elevated factor XI iv. Elevated lipoprotein (a) d. Acquired thrombophilias i. Lupus anticoagulant ii. Anti-cardiolipin antibodies/Beta2 glycoprotein antibodies iii. Antiphospholipid syndrome Exclusion Criteria 1. Acquired thrombophilia secondary to medications (birth control pills or hormone replacement therapy, overweight or obesity, smoking, cancer, pregnancy, surgery, injury, prolonged inactivity/bedrest, heart failure, inflammatory bowel disease, or kidney disease Non-Neoplastic Hematologic Conditions Cohort Inclusion Criteria Participants who meet the following inclusion criteria are eligible for enrollment into this cohort: 1. Having any congenital or acquired non-neoplastic hematologic disorder not included in any other cohort Exclusion Criteria None |
Country | Name | City | State |
---|---|---|---|
United States | Akron Children's Hospital - Showers Center for Cancer & Blood Disorders | Akron | Ohio |
United States | Comprehensive Bleeding Disorders Center at Emory University and Children's Healthcare of Atlanta | Atlanta | Georgia |
United States | Emory/Children's Health Care of Atlanta | Atlanta | Georgia |
United States | University of Colorado Denver Hemophilia and Thrombosis Center | Aurora | Colorado |
United States | Johns Hopkins University Hemophilia Treatment Center | Baltimore | Maryland |
United States | Massachusetts General Hospital Comprehensive Hemophilia and Thrombosis Treatment Center | Boston | Massachusetts |
United States | Montefiore Medical Center | Bronx | New York |
United States | Western New York BloodCare | Buffalo | New York |
United States | Comprehensive Hemophilia Treatment Center, University of North Carolina at Chapel Hill | Chapel Hill | North Carolina |
United States | St. Jude Affiliate Clinic at Novant Health Hemby Children's Hospital | Charlotte | North Carolina |
United States | Rush University Medical Center | Chicago | Illinois |
United States | Cincinnati Children's Hospital Medical Center, Hemophilia & Thrombosis Center | Cincinnati | Ohio |
United States | University of Cincinnati Medical Center Hemophilia Treatment Center | Cincinnati | Ohio |
United States | University Hospitals Health System Cleveland | Cleveland | Ohio |
United States | Nationwide Children's Hospital Columbus | Columbus | Ohio |
United States | North Texas Comprehensive Hemophilia Treatment Center | Dallas | Texas |
United States | North Texas Hemophilia and Thrombosis Program - Pediatric Program / Center for Cancer & Blood Disorders | Dallas | Texas |
United States | Dayton Children's Hemostasis and Thrombosis Center | Dayton | Ohio |
United States | Central Michigan Children's Hospital of Michigan | Detroit | Michigan |
United States | Henry Ford Health System Bleeding and Thrombosis Treatment Center | Detroit | Michigan |
United States | Fort Worth Bleeding Disorders Program | Fort Worth | Texas |
United States | University of Florida Hemophilia Treatment Center | Gainesville | Florida |
United States | Hemophilia Outreach Center Green Bay | Green Bay | Wisconsin |
United States | East Carolina University Hemophilia Treatment Center | Greenville | North Carolina |
United States | Gulf States Hemophilia and Thrombophilia Center | Houston | Texas |
United States | Texas Children's Hemophilia & Thrombosis Center/Baylor College of Medicine | Houston | Texas |
United States | Northwell Health Hemostasis and Thrombosis Center at Long Island Jewish and Cohen Children's Medical Center | Hyde Park | New York |
United States | Indiana Hemophilia and Thrombosis Center | Indianapolis | Indiana |
United States | Iowa Hemophilia and Thrombosis Center | Iowa City | Iowa |
United States | Children's Mercy Hospital - Kansas City | Kansas City | Missouri |
United States | Cure 4 The Kids Foundation | Las Vegas | Nevada |
United States | Arkansas Center for Bleeding Disorders | Little Rock | Arkansas |
United States | Orthopaedic Institute for Children HTC | Los Angeles | California |
United States | Mississippi Center for Advanced Medicine | Madison | Mississippi |
United States | St. Jude Children's Research Hospital | Memphis | Tennessee |
United States | Comprehensive Center for Bleeding Disorders | Milwaukee | Wisconsin |
United States | Vanderbilt University Medical Center | Nashville | Tennessee |
United States | Yale Hemophilia Treatment Center | New Haven | Connecticut |
United States | Louisiana Center for Bleeding and Clotting Disorders, Tulane University | New Orleans | Louisiana |
United States | Weill Cornell Medical College - New York Presbyterian Hospital | New York | New York |
United States | Newark Beth Israel Medical Center - Hemophilia Center | Newark | New Jersey |
United States | Arnold Palmer Hospital for Children - The Haley Center for Children's Cancer and Blood Disorders | Orlando | Florida |
United States | Bleeding and Clotting Disorders Institute | Peoria | Illinois |
United States | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
United States | Penn Comprehensive Hemophilia and Thrombophilia Program/Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania |
United States | Arizona Hemophilia and Thrombosis Treatment Center at Phoenix Children's Hospital | Phoenix | Arizona |
United States | Hemophilia Center of Western Pennsylvania | Pittsburgh | Pennsylvania |
United States | Rhode Island Hospital Hemostasis and Thrombosis Center | Providence | Rhode Island |
United States | Hemostasis and Thrombosis Center of Nevada | Reno | Nevada |
United States | American Thrombosis and Hemostasis Network | Rochester | New York |
United States | Mayo Comprehensive Hemophilia Center | Rochester | Minnesota |
United States | University of California at Davis Hemophilia Treatment Center | Sacramento | California |
United States | The John Bouhasin Center for Children with Bleeding Disorders | Saint Louis | Missouri |
United States | Johns Hopkins All Children's Hospital | Saint Petersburg | Florida |
United States | South Texas Comprehensive Hemophilia and Thrombophilia Treatment Center | San Antonio | Texas |
United States | Loma Linda Hemoglobinopathy and Inherited Bleeding Disorder Program | San Bernardino | California |
United States | Hemophilia & Thrombosis Treatment Center at UC San Diego Health | San Diego | California |
United States | Rady Children's Hospital San Diego | San Diego | California |
United States | Willett Children's Hemophilia Treatment Center at Memorial Health | Savannah | Georgia |
United States | Maine Hemophilia and Thrombosis Center | Scarborough | Maine |
United States | Washington Center for Bleeding Disorders | Seattle | Washington |
United States | Louisiana Center for Advanced Medicine | Slidell | Louisiana |
United States | St. Joseph's Hospital Center for Bleeding & Clotting Disorders | Tampa | Florida |
United States | Northwest Ohio Hemophilia Treatment Center at the Toledo Hospital | Toledo | Ohio |
United States | Children's National Hemophilia Center | Washington | District of Columbia |
United States | Georgetown University | Washington | District of Columbia |
United States | Wake Forest University Health Sciences | Winston-Salem | North Carolina |
Lead Sponsor | Collaborator |
---|---|
American Thrombosis and Hemostasis Network | CSL Behring, Genentech, Inc., Hemab Therapeutics, Hemophilia of Georgia, Inc., Pfizer, Sanofi |
United States,
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Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | To describe real-world effectiveness of therapies by evaluating for Goal attainment | Measured by GOAL-Hem for those participants that opt into this measurement | 15 years | |
Other | To describe real-world effectiveness of therapies by evaluating for Patient Reported Outcomes (PROs) | Measured by the Patient Reported Outcomes Measurement Information System (PROMIS) Profile 29/25/Parent Proxy | 15 years | |
Other | To describe real-world effectiveness of therapies by evaluating treatment adherence | Measured by the Global Adherence Rating (GAR) | 15 years | |
Other | To describe real-world effectiveness of therapies by evaluating health utility | Measured by the EQ-5D-5L | 15 years | |
Primary | To determine the safety of therapies used in the treatment of participants with congenital or acquired non-neoplastic blood disorders and connective tissue disorders with bleeding tendency. | Safety will be measured by those events in the European Safety Surveillance (EUHASS). Allergic or other acute events Treatment-emergent side effects of therapy Transfusion transmitted infections Inhibitor development Thrombosis Cardiovascular events Malignancies Neurological events Death In addition to the modified EUHASS endpoints, the following events will be collected as adverse events of special interest (AESI): The occurrence of thrombotic microangiopathies, injection site reactions and cases of potential drug-induced liver injury The development of anti-drug antibodies, to be measured and confirmed, if feasible Severe, unanticipated bleeding Hospitalizations Glomerulonephritis Additional safety events of interest (TBD) may be collected. These may be chosen from drug development profiles based on investigational studies, package inserts, and emerging clinical and scientific observations. |
15 years | |
Primary | To describe the safety and tolerability of efanesoctocog alfa in previously untreated patients (PUPs) with hemophilia A without a history of inhibitors. | Safety and tolerability will be measured by Annualized Bleed Rate (ABR), number of doses to treat a bleed, doses during perioperative surgery, and clinical patient reported outcomes (PROs) in this population. | 7 years | |
Secondary | To establish a platform to support study Arms and Modules for participants with bleeding, clotting, other non-neoplastic blood disorders, and connective tissue disorders with bleeding tendency. | For each Arm, a brief set of data elements of interests will be developed and reported for study participants. | 15 years | |
Secondary | To describe medication dosing regimens in the above conditions. | This objective will be evaluated by: Determining the number of participants who initiate and/or switch treatment with non-factor products and participants' reasons for initiating and/or switching treatment with non-factor products Determining the number of participants who do not initiate treatment with non-factor products Determining the number of participants who switch between different non-factor products and the participants' reasons for switching non-factor products Determining the number of participants who discontinue treatment with non-factor products and participants' reasons for discontinuing treatment with non-factor products |
15 years | |
Secondary | To grow and evolve a biorepository for current and future research through the collection of biospecimens from every person enrolled on this protocol. | All participants will have the option of having specimens drawn (about 5mL each) at baseline to be stored in the ATHN Research Biorepository (ARB). | 15 years | |
Secondary | To describe real-world effectiveness of therapies by evaluating for Health care utilization | Measured by number and type of visits and hospitalizations per year. | 15 years | |
Secondary | To describe bleeding events, changes in overall bleeding, and annualized bleeding rate (ABR) as measured by individual bleeding components. | This objective will be calculated per ISTH Bleeding Assessment Tool (ISTH BAT), and if applicable, a Pictorial Bleeding Assessment Chart (PBAC), for applicable diagnoses. | 15 years |
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