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

Recruiting

• Conditions: Hematologic Disorder; Bleeding Disorder; Connective Tissue Disorder; Hemophilia; Thrombosis; Von Willebrand Diseases; Thrombophilia; Rare Bleeding Disorder; Platelet Disorder; Factor IX Deficiency

• Registration Number: NCT04398628
• Lead Sponsor: American Thrombosis and Hemostasis Network

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-5-11
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Participants who meet the following inclusion criteria and none of the exclusion criteria<br>are eligible for enrollment in the base study:<br><br>Inclusion Criteria:<br><br> 1. Any age<br><br> 2. Having a congenital or acquired non-neoplastic hematologic disorder; or<br><br> 3. Having a bleeding phenotype as indicated by an age adjusted abnormal ISTH Bleeding<br> Assessment Tool score with an unknown diagnosis; or<br><br> 4. Connective tissue disorder with bleeding tendency as indicated by an age adjusted<br> abnormal ISTH Bleeding Assessment Tool score.<br><br>Exclusion Criteria:<br><br> 1. Does not qualify for inclusion in a cohort 2. Unable to give informed consent or<br> assent 3. Unwilling to perform study procedures<br><br>Cohort Participant Selection<br><br>Each participant is to be enrolled in the cohort for which they qualify as defined below.<br><br>Hemophilia Cohort<br><br>Inclusion Criteria:<br><br>Participants who meet any of the following inclusion criteria are eligible for enrollment<br>into this cohort:<br><br> 1. Factor VIII or factor IX activity < 50%, without another explanation for low<br> clotting factor other than congenital hemophilia or being a known carrier for<br> congenital hemophilia; OR<br><br> 2. Being a known carrier for congenital hemophilia with a factor VIII or factor IX<br> activity greater than or equal to 50% with or without a bleeding phenotype as<br> indicated by an age-adjusted abnormal ISTH Bleeding Assessment Tool score; OR<br><br> 3. Known congenital hemophilia that have a factor level >50% after receiving vector; OR<br><br> 4. Acquired hemophilia<br><br>Exclusion Criteria:<br><br>None<br><br>Von Willebrand Disease Cohort<br><br>Inclusion Criteria:<br><br>Participants who meet the following inclusion criteria are eligible for enrollment into<br>this cohort:<br><br> 1. Meeting the definition of VWD or low VWF per most recent international guidelines<br><br>Exclusion Criteria:<br><br>None<br><br>Congenital Platelet Disorders Cohort<br><br>Inclusion Criteria:<br><br>Participants who meet the following inclusion criteria are eligible for enrollment into<br>this cohort:<br><br> 1. Abnormalities of platelet function<br><br> 1. Glanzmann thrombasthenia (GPIIb or GPIIIa)<br><br> 2. Bernard-Soulier syndrome (GPIbalpha, GPIbbeta, or GPIX)<br><br> 2. Abnormalities of platelet granules<br><br> 3. Abnormalities of platelet signal transduction<br><br> 4. Abnormalities of platelet secretion<br><br> 5. Collagen Receptor Defect<br><br> 6. ADP Receptor Defect<br><br> 7. Thromboxane Receptor Defect<br><br> 8. Giant Platelet Disorder<br><br> 9. Abnormalities in platelet aggregation testing due to another or unknown cause (not<br> drug related)<br><br>Exclusion Criteria:<br><br>Platelet disorders secondary to medications or other substances<br><br>Rare Disorders Cohort<br><br>Inclusion Criteria:<br><br>Participants who meet the following inclusion criteria are eligible for enrollment into<br>this cohort:<br><br> 1. Have an established Rare Coagulation Disorder (RCD) diagnosis of one of the<br> following:<br><br> 1. PAI-1 deficiency<br><br> 2. Factor I, II, V, VII, X, XI, XIII deficiencies<br><br> 3. Combined FV and FVIII deficiency<br><br> 4. Plasminogen deficiency<br><br> 5. Decreased tissue plasminogen activator<br><br> 6. Afibrinogenemia/hypofibrinogenemia/dysfibrinogenemia<br><br>Exclusion Criteria:<br><br>None<br><br>Bleeding NOS Cohort<br><br>Inclusion Criteria:<br><br>Participants who meet the following inclusion criteria are eligible for enrollment into<br>this cohort:<br><br> 1. Have a bleeding phenotype as indicated by an age-adjusted abnormal ISTH Bleeding<br> Assessment Tool score with an unknown diagnosis; OR<br><br> 2. Connective tissue disorder with bleeding tendency as indicated by an age-adjusted<br> abnormal ISTH Bleeding Assessment Tool score<br><br>Exclusion Criteria:<br><br>None<br><br>Thrombosis/Thrombophilia Cohort<br><br>Inclusion Criteria<br><br>Participants who meet the following inclusion criteria are eligible for enrollment into<br>this cohort:<br><br> 1. Have a prior history of arterial or venous thrombosis<br><br> 2. Patients with a known congenital or acquired thrombophilia with or without a<br> thrombosis a. Common congenital thrombophilias:: i. Protein C deficiency ii. Protein<br> S deficiency iii. Antithrombin deficiency iv. Factor V Leiden v. Prothrombin gene<br> mutation b. Rare genetic factors i. Hyperhomocysteinemia c. Indeterminate genetic<br> factors i. Elevated factor VIII ii. Elevated factor IX iii. Elevated factor XI iv.<br> Elevated lipoprotein (a) d. Acquired thrombophilias i. Lupus anticoagulant ii.<br> Anti-cardiolipin antibodies/Beta2 glycoprotein antibodies iii. Antiphospholipid<br> syndrome<br><br>Exclusion Criteria<br><br> 1. Acquired thrombophilia secondary to medications (birth control pills or hormone<br> replacement therapy, overweight or obesity, smoking, cancer, pregnancy, surgery,<br> injury, prolonged inactivity/bedrest, heart failure, inflammatory bowel disease, or<br> kidney disease<br><br>Non-Neoplastic Hematologic Conditions Cohort<br><br>Inclusion Criteria<br><br>Participants who meet the following inclusion criteria are eligible for enrollment into<br>this cohort:<br><br> 1. Having any congenital or acquired non-neoplastic hematologic disorder not included<br> in any other cohort<br><br>Exclusion Criteria<br><br>None<br><br>Previously Untreated Patients Arm Eligibility Criteria<br><br>Inclusion Criteria Diagnosis of congenital hemophilia A (FVIII <40%) or hemophilia B (FIX<br><40% or below lower limit for age)<br><br> 1. Age <18 years at time of enrollment<br><br> 2. Parent or authorized guardian or legally authorized representative (LAR) can provide<br> informed consent<br><br> 3. Care established at one of the participating HTCs<br><br>Exclusion Criteria<br><br> 1. CFC exposure, fresh frozen plasma (FFP), cryoprecipitate, and single donor platelets<br> >3 EDs<br><br> 2. Concomitant diagnosis with another bleeding disorder<br><br> 3. History of confirmed inhibitor<br><br>INHIBIT Module Eligibility Criteria:<br><br>Inclusion Criteria<br><br> 1. Diagnosis of severe factor VIII deficiency with baseline factor VIII level <1%<br><br> 2. Initiating or plan to initiate prophylaxis with emicizumab or factor replacement<br><br> 3. Factor exposure, plasma/FFP, cryo, and single donor platelets =3 EDs<br><br> 4. =5 years of age<br><br>Exclusion Criteria<br><br> 1. Concomitant diagnosis with bleeding disorder other than hemophilia A<br><br> 2. Immune disorder<br><br> 3. Factor exposure, plasma/FFP, cryo, and single donor platelets >3 EDs<br><br> 4. Previous history or presence of factor VIII inhibitor<br><br>ALTUVIIIO® Module Eligibility Criteria:<br><br><br><br> - People with severe HA with a baseline FVIII activity of less than 1%. (While<br> inclusion for participation in ATHN Transcends lists <5% FVIII activity, this<br> proposed module will limit enrollment to people with FVIII activity levels of <1%)<br><br> - <18 years of age<br><br> - No history of FVIII inhibitor<br><br> - Sex at birth of male, female, or intersex<br><br> - Participants may be exposed to unfractionated blood components, no more than one<br> dose of FVIII concentrate other than efanesoctocog alfa and up to three doses of<br> efanesoctocog alfa prior to enrollment<br><br> - Potential participants who have a history of bleeding will be eligible for<br> participation if they meet all other inclusion criteria<br><br>Exclusion criteria:<br><br> - Not meeting all t

Exclusion Criteria

Not provided

Study & Design

• Study Type: Observational
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.;To describe the safety and tolerability of efanesoctocog alfa in previously untreated patients (PUPs) with hemophilia A without a history of inhibitors.

Secondary Outcome Measures

Name	Time	Method
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.;To describe medication dosing regimens in the above conditions.;To grow and evolve a biorepository for current and future research through the collection of biospecimens from every person enrolled on this protocol.;To describe real-world effectiveness of therapies by evaluating for Health care utilization;To describe bleeding events, changes in overall bleeding, and annualized bleeding rate (ABR) as measured by individual bleeding components.