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

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04398628
• Other study ID #: ATHN Transcends
• Status: Recruiting
• Start date: September 30, 2020
• Est. completion date: December 2035

Study information

• Verified date: June 2024
• Source: American Thrombosis and Hemostasis Network
• Contact: Carol Fedor, ND, RN, CCRC
• Phone: 800-360-2846
• Email: cfedor[@]athn.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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)

Description:

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

Julie Jaffray, MD 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 Julie Jaffray, MD 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

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

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.

Recruitment information / eligibility

• 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

Previously Untreated Patients Arm Eligibility Criteria

Inclusion Criteria Diagnosis of congenital hemophilia A (FVIII <40%) or hemophilia B (FIX <40% or below lower limit for age)

1. Age <18 years at time of enrollment

2. Parent or authorized guardian or legally authorized representative (LAR) can provide informed consent

3. Care established at one of the participating HTCs

Exclusion Criteria

1. CFC exposure, fresh frozen plasma (FFP), cryoprecipitate, and single donor platelets >3 EDs

2. Concomitant diagnosis with another bleeding disorder

3. History of confirmed inhibitor

INHIBIT Module Eligibility Criteria:

Inclusion Criteria

1. Diagnosis of severe factor VIII deficiency with baseline factor VIII level <1%

2. Initiating or plan to initiate prophylaxis with emicizumab or factor replacement

3. Factor exposure, plasma/FFP, cryo, and single donor platelets =3 EDs

4. =5 years of age

Exclusion Criteria

1. Concomitant diagnosis with bleeding disorder other than hemophilia A

2. Immune disorder

3. Factor exposure, plasma/FFP, cryo, and single donor platelets >3 EDs

4. Previous history or presence of factor VIII inhibitor

ALTUVIIIO® Module Eligibility Criteria:

Inclusion criteria:

• People with severe HA with a baseline FVIII activity of less than 1%. (While inclusion for participation in ATHN Transcends lists <5% FVIII activity, this proposed module will limit enrollment to people with FVIII activity levels of <1%)

• <18 years of age

• No history of FVIII inhibitor

• Sex at birth of male, female, or intersex

• Participants may be exposed to unfractionated blood components, no more than one dose of FVIII concentrate other than efanesoctocog alfa and up to three doses of efanesoctocog alfa prior to enrollment

• Potential participants who have a history of bleeding will be eligible for participation if they meet all other inclusion criteria

Exclusion criteria:

• Not meeting all the inclusion criteria

• Any exposure to blood components or FVIII replacement products except as described in the inclusion criteria

• History of positive inhibitor testing

• History of hypersensitivity reactions associated with efanesoctocog alfa administration

• Any concurrent clinically significant major disease that, in the investigator's opinion, would make the participant unsuitable for enrollment.

• The presence of any additional inherited bleeding disorder diagnosis

• Enrollment in a concurrent clinical interventional drug study

• Intake of an Investigational Medicinal Product within three months prior to inclusion in this study

• Inability to comply with study requirements

• Other, unspecified reasons that, in the investigator's opinion, make the participant unsuitable for enrollment.

Hemophilia Natural History Arm Eligibility Criteria:

Inclusion Criteria

1. Congenital hemophilia A or B of any severity with or without inhibitors receiving a current therapy, a non-factor product, or for whom use of a non-factor product is a possibility.

Exclusion Criteria

1. Presence of any known bleeding disorder other than congenital hemophilia A or B

2. Presence of concurrent hemophilia and a second hemostatic defect (low Von Willebrand Factor (VWF) without VWD diagnosis is not excluded)

3. Unable or unwilling to comply with the study arm protocol.

Rebinyn® Module Eligibility Criteria

Inclusion Criteria:

Participants who meet the following inclusion criteria at the time of screening are eligible to enroll in the study module.

Rebinyn® Cohort

1. Has provided signed written consent for the Rebinyn® Module before any study-related activities.

2. Male participants, at any age with hemophilia B, naïve or minimally exposed (up to 3 EDs) to nonacog beta pegol treatment at time of study enrollment.

3. Decision to initiate treatment with commercially available nonacog beta pegol has been made by the participant(s)/Legally Authorized Representative(s) (LAR(s)) and the treating physician before and independently from the decision to include the participant in this study.

Rebinyn® RWE Cohort

1. Has provided signed written consent for ATHN Transcends Study before any study-related activities.

2. Currently treated with nonacog beta pegol

3. Any age

Exclusion Criteria:

Participants who fall into any of the following exclusion criteria at the time of screening are not eligible for enrollment into the study module:

Rebinyn® Cohort

1. Previous participation in this study. Participation is defined as having given informed consent in this study.

2. Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation, including a diagnosis or suspicion of attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) per the discretion of the Principal Investigator.

3. Known or suspected hypersensitivity to nonacog beta pegol or related products.

4. Clinical suspicion or presence of FIX inhibitor at time of inclusion.

5. Inability or unwillingness to undergo the neurological assessment/ structured developmental history.

Rebinyn® RWE Cohort 1. None

Hemophilia Gene Therapy Outcomes Arm Eligibility Criteria:

Inclusion Criteria

1. Hemophilia A or B of any severity with or without inhibitors having received or will receive a hemophilia gene transfer product in the next 6 months.

2. Age 18 years and older

3. Able to give informed consent.

Exclusion Criteria None

HEMGENIX® Module Eligibility Criteria

Inclusion Criteria:

HEMGENIX Cohort • Age 18 years of age or older

• Treatment with commercial HEMGENIX

• Have provided signed written informed consent within 3 months before or within 6 months after HEMGENIX treatment, or within 6 months of when the study is initiated at the treating site.

Exclusion Criteria, both cohorts:

• Have been treated with etranacogene dezaparvovec in a clinical trial.

Congenital Platelet Disorders Arm Eligibility Criteria:

Inclusion Criteria

1. Platelet adhesion defect

1. Bernard Soulier syndrome (Defective GPIb-IX-V receptor, impaired adhesion to VWF)

2. Velocardio-facial syndrome/DiGeorge syndrome (Defective GPIb-IX-V receptor)

3. Platelet type vWD (Defective GPIb-IX-V, gain of function interaction between VWF-GP1ba)

2. Platelet aggregation defect

1. Glanzmann thrombasthenia (Defective integrin aIIbß3 (GPIIb/IIIa)

2. Platelet aggregation defect, NOS

3. Agonist receptor defects

1. Epinephrine

2. ADP

3. Collagen

4. Thromboxane A2

4. Platelet signaling defects

1. Cyclooxygenase deficiency (PTGS1 mutation)

2. Phospholipase A2 deficiency

3. Thromboxane synthase deficiency (TBXAS1 mutation)

4. G protein activation defect (GNAS mutation)

5. Scott syndrome (defect in phosphatidyl serine translocation)

5. Platelet Granule disorders

1. Dense granule storage pool disorder • Hermansky Pudlak syndrome

• Chediak Higashi syndrome

• Griscelli syndrome

2. Alpha granule storage pool disorder

• Grey platelet syndrome

• Arthrogryposis-Renal Dysfunction-Cholestasis (ARC) syndrome

• Quebec platelet disorder

• Paris-Trousseau syndrome

3. Combined alpha delta granule deficiency

6. Platelet cytoskeletal structure defects

1. Wiskott Aldrich syndrome

2. MYH9 associated disorders (myosin heavy chain)

• May Hegglin syndrome

• Fechtner syndrome

• Sebastian syndrome

• Epstein syndrome

3. Other mutations • FLNA mutations (Filamin) • DIAPH1 (Actin and microtubules) • ACTN1 (alpha actinin) • TPM4 (tropomyosin)

• TUBB1 (beta tubulin)

7. Other Congenital thrombocytopenias

1. Familial platelet disorders and predisposition to AML (RUNX1)

2. X linked thrombocytopenia with dyserythropoiesis (GATA1)

3. Congenital amegakaryocytic thrombocytopenia (MPL)

Exclusion Criteria

1. Diagnosis of von Willebrand disease (Meeting the definition of VWD or low VWF per most recent international guidelines)

2. Diagnosis of Hemophilia A or Hemophilia B (Factor VIII or IX = 40%)

FIX Prophylaxis Cohort

• Age 18 years of age or older

• Treatment with FIX prophylaxis therapy

• Has provided signed written consent at any time for ATHN Transcends Study

Glanzmann Thrombasthenia (GT) Module Eligibility Criteria:

Inclusion Criteria

1. Participant has signed the informed consent/assent form 2. Participant has flow cytometry or aggregometry or genetics confirmed GT 3. Participant is willing to perform study procedures, including daily bleed tracking for 3 months

Exclusion Criteria None

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Bleeding Disorder
• Blood Coagulation Disorders
• Blood Platelet Disorders
• Connective Tissue Diseases
• Connective Tissue Disorder
• Factor IX Deficiency
• Factor VIII Deficiency
• Hematologic Diseases
• Hematologic Disorder
• Hemophilia
• Hemophilia A
• Hemophilia B
• Hemorrhage
• Hemorrhagic Disorders
• Hemostatic Disorders
• Platelet Disorder
• Rare Bleeding Disorder
• Sickle Cell Disease
• Thalassemia
• Thrombophilia
• Thrombosis
• Von Willebrand Diseases

Locations

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	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

Sponsors (8)

Lead Sponsor	Collaborator
American Thrombosis and Hemostasis Network	CSL Behring, Genentech, Inc., Hemab Therapeutics, Hemophilia of Georgia, Inc., Novo Nordisk A/S, Pfizer, Sanofi

Country where clinical trial is conducted

United States, 

References & Publications (8)

Braunholtz DA, Edwards SJ, Lilford RJ. Are randomized clinical trials good for us (in the short term)? Evidence for a "trial effect". J Clin Epidemiol. 2001 Mar;54(3):217-24. doi: 10.1016/s0895-4356(00)00305-x. — View Citation

https://www.clinicaltrials.gov/ct2/results?cond=Hematologic+Diseases&term=&cntry=&state=&city=&dist=. Accessed 04 Jul 2019

https://www.fda.gov/drugs/resources-information-approved-drugs/hematologyoncology-cancer-approvals-safety-notifications. Accessed 04 Jul 2019

Iorio A, Keepanasseril A, Foster G, Navarro-Ruan T, McEneny-King A, Edginton AN, Thabane L; WAPPS-Hemo co-investigator network. Development of a Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo): Study Protocol. JMIR Res Protoc. 2016 Dec 15;5(4):e239. doi: 10.2196/resprot.6558. — View Citation

Konkle BA, Recht M; members of Working Group 2, the NHLBI State of the Science Workshop on factor VIII inhibitors: Generating a national blueprint for future research. The national blueprint for 21st century data and specimen collection and observational cohort studies: NHLBI State of the Science Workshop on factor VIII inhibitors. Haemophilia. 2019 Jul;25(4):590-594. doi: 10.1111/hae.13772. — View Citation

Unger JM, Barlow WE, Martin DP, Ramsey SD, Leblanc M, Etzioni R, Hershman DL. Comparison of survival outcomes among cancer patients treated in and out of clinical trials. J Natl Cancer Inst. 2014 Mar;106(3):dju002. doi: 10.1093/jnci/dju002. Epub 2014 Mar 13. — View Citation

Weijer C, Freedman B, Fuks A, Robbins J, Shapiro S, Skrutkowska M. What difference does it make to be treated in a clinical trial? A pilot study. Clin Invest Med. 1996 Jun;19(3):179-83. — View Citation

West J, Wright J, Tuffnell D, Jankowicz D, West R. Do clinical trials improve quality of care? A comparison of clinical processes and outcomes in patients in a clinical trial and similar patients outside a trial where both groups are managed according to a strict protocol. Qual Saf Health Care. 2005 Jun;14(3):175-8. doi: 10.1136/qshc.2004.011478. — View Citation

Outcome

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