ATHN Transcends: A Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment in People With Non-Neoplastic Hematologic Disorders
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 3,000
- 试验地点
- 138
- 主要终点
- To determine the safety of therapies used in the treatment of participants with congenital or acquired non-neoplastic, bleeding and clotting disorders and connective tissue disorders with bleeding tendency (blood disorders).
研究概览
简要总结
In parallel with the growth of ATHN's clinical studies, the number of new therapies for all blood disorders is increasing significantly. Some of the recently FDA-approved therapies for congenital and acquired hematologic conditions have not yet demonstrated 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.2,3,4,5
In 2019 alone, the FDA has issued approvals for 24 new therapies for congenital and acquired hematologic conditions.6 In addition, almost 10,000 new studies for hematologic diseases are currently registered on www.clinicaltrials.gov.7
With this increase in potential new therapies possible, 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. 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.8
详细描述
This is a longitudinal, natural history observational cohort study being conducted at approximately 150 ATHN-affiliated sites with a target accrual of 3,000 participants. Participants will be followed for a minimum of 15 years on an assigned arm within a cohort; however, arm or module participation may last longer, and participants will continue participation in the arm or module for its duration. Harmonized data elements will be collected at the time of enrollment, semi-annually (every 6 months), annually, ad hoc, and as defined by the terms of individual arms and modules. 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 are developed to advance the exploration of blood disorders disease specific insights by ATHN and its partners. 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
Co- Principal Investigators:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who meet the following inclusion criteria and none of the
排除标准
- •are eligible for enrollment in one of the open disease-specific arms.
- •Inclusion Criteria:
- •Having a congenital or acquired blood disorder; or
- •Having a bleeding phenotype as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score with an unknown diagnosis; or
- •Connective tissue disorder with bleeding tendency as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score.
- •Eligible for a currently active disease-specific arm.
- •Concurrent enrollment in the ATHNdataset or current ATHNdataset participant.
- •Exclusion Criteria:
- •1. Does not qualify for inclusion in a currently activedisease-specific arm; participants may be eligible to enroll as future cohorts and arms are activated;
- •Unable to give informed consent or assent
- •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:
- •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
- •Carrier for congenital hemophilia with a factor VIII >=50% or factor IX activity >=50% with or without a bleeding phenotype as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years OR
- •Known congenital hemophilia that have a factor level >50% after receiving vector, OR
- •Acquired hemophilia.
- •Exclusion Criteria:
- •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:
- •Congenital Platelet Disorders Cohort
- •Inclusion Criteria:
- •Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:
- •Abnormalities of platelet function a. Glanzmann thrombasthenia (GPIIb or GPIIIa) b. Bernard-Soulier syndrome (GPIbalpha, GPIbbeta, or GPIX)
- •Abnormalities of platelet granules
- •Abnormalities of platelet signal transduction
- •Abnormalities of platelet secretion
- •Collagen Receptor Defect
- •ADP Receptor Defect
- •Thromboxane Receptor Defect
- •Giant Platelet Disorder
- •Abnormalities in platelet aggregation testing due to another or unknown cause (not drug related)
- •Exclusion Criteria:
- •1. 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:
- •PAI-1 deficiency
- •Factor I, II, V, VII, X, XI, XIII deficiencies
- •Combined FV and FVIII deficiency
- •Plasminogen deficiency
- •Decreased tissue plasminogen activator
- •Afibrinogenemia/hypofibrinogenemia/dysfibrinogenemia
- 另有 172 项未显示
研究组 & 干预措施
Congenital Platelet Disorders
This cohort includes one Arm and Module:
Congenital Platelet Disorders (CPD) Natural History Arm Glanzmann Thrombasthenia (GT) Module
Rare Disorders
No arms or modules
Bleeding NOS
No arms or modules
Thrombosis/Thrombophilia
No arms or modules
Non-Neoplastic Hematologic Conditions
No arms or modules
Hemophilia
This cohort includes three Arms and six Modules:
Previously Untreated Patients (PUPs) Arm
Efanestoctocog alfa (ALTUVIIIO®) Module
INHIBIT Module
Hemophilia Natural History Arm
Emicizumab (Hemlibra®) Module
Nonacog beta pegol (Rebinyn®)Module
Distress Module
Hemophilia Gene Therapy Outcomes Arm
Etranacogene dezaparvovec (HEMGENIX®) Module
Von Willebrand Disease
No arms or modules
结局指标
主要结局
To determine the safety of therapies used in the treatment of participants with congenital or acquired non-neoplastic, bleeding and clotting disorders and connective tissue disorders with bleeding tendency (blood disorders).
时间窗: 15 years
Safety will be measured by those events in the European Safety Surveillance (EUHASS)1: 1. Allergic or other acute events 2. Treatment-emergent side effects of therapy 3. Transfusion transmitted infections 4. Inhibitor development 5. Thrombosis 6. Cardiovascular events 7. Malignancies 8. Neurological events 9. Death In addition to the modified EUHASS endpoints, the following events will be collected as adverse events of special interest (AESI): 1. The occurrence of thrombotic microangiopathies, injection site reactions and cases of potential drug-induced liver injury 2. The development of anti-drug antibodies, to be measured and confirmed, if feasible 3. Severe, unanticipated bleeding 4. Hospitalizations 5. Glomerulonephritis 6. Any arm or module-specific AESI as stated in their corresponding Safety Assessment section Additional safety events of interest may be collected.
To determine the safety of therapies used in the treatment of participants with congenital or acquired non-neoplastic, bleeding and clotting disorders and connective tissue disorders with bleeding tendency (blood disorders).
时间窗: 15 years
Safety will be measured by those events in the European Safety Surveillance (EUHASS)1: 1. Allergic or other acute events 2. Treatment-emergent side effects of therapy 3. Transfusion transmitted infections 4. Inhibitor development 5. Thrombosis 6. Cardiovascular events 7. Malignancies 8. Neurological events 9. Death In addition to the modified EUHASS endpoints, the following events will be collected as adverse events of special interest (AESI): 1. The occurrence of thrombotic microangiopathies, injection site reactions and cases of potential drug-induced liver injury 2. The development of anti-drug antibodies, to be measured and confirmed, if feasible 3. Severe, unanticipated bleeding 4. Hospitalizations 5. Glomerulonephritis 6. Any arm or module-specific AESI as stated in their corresponding Safety Assessment section Additional safety events of interest may be collected.
次要结局
- To establish a platform to support study arms and modules for participants with blood disorders.(15 years)
- To establish a platform to support study arms and modules for participants with blood disorders.(15 years)
- To describe medication dosing regimens in participants with blood disorders.(15 years)
- To describe real-world effectiveness of therapies used for participants with blood disorders.(15 years)
- To grow and evolve the ATHN Transcends Biorepository for current and future research through the collection of biospecimens from participants enrolled on this protocol(15 years)
- To describe bleeding events, changes in overall bleeding, and annualized bleeding rate (ABR) as measured by individual bleeding components.(15 years)