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ATHN 8: PUPs Matter Study

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ClinicalTrials.gov Identifier: NCT03818529
Recruitment Status : Recruiting
First Posted : January 28, 2019
Last Update Posted : August 19, 2020
Sponsor:
Collaborators:
CSL Behring
Octapharma
Takeda
Information provided by (Responsible Party):
American Thrombosis and Hemostasis Network

Tracking Information
First Submitted Date January 23, 2019
First Posted Date January 28, 2019
Last Update Posted Date August 19, 2020
Actual Study Start Date October 3, 2018
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 24, 2019)
Determine percentage of patients with confirmed inhibitors [ Time Frame: 6 years ]
Participants will be followed to assess inhibitor development (per CDC laboratory criteria; >0.5 Nijmegen Bethesda Units for hemophilia A and >0.3 Nijmegen Bethesda Units for hemophilia B) within 50 exposure days. Blood specimens will be submitted to the CDC for inhibitor testing at various time points outlined in the protocol.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: February 1, 2019)
  • Determine risk factors including genetic variants associated with inhibitor development in PUPs [ Time Frame: 6 years ]
    The study will provide a systematic approach to data collection by using the ATHN System to provide database infrastructure and data collection methods to evaluate determinants of inhibitor formation.
  • Determine percentage of eligible participants enrolled at each site [ Time Frame: 6 years ]
    Sites will report number of eligible participants and number of participants enrolled to determine the percentage of enrollment.
  • Determine mean age of diagnosis and first exposure to factor treatment product [ Time Frame: 6 years ]
    Sites will document the date of diagnosis and the date of first exposure to clotting factor treatment product.
  • Determine the number of exposure days prior to inhibitor development [ Time Frame: 6 years ]
    Sites and participants will work together to provide detailed records of exposure days to clotting factor replacement products. The CDC will act as the central laboratory for the study and provide inhibitor testing.
  • Report bleeding complications that occur within the first 50 ED [ Time Frame: 6 years ]
    The documentation of bleeding events in the study records will be based on the review of bleeding and infusion records provided by the participant or the from medical chart review during the first 50 exposure days to clotting factor replacement product.
  • Summarize factor replacement dosing regimen prescribed to this study population within the first 50 ED [ Time Frame: 6 years ]
    A summary of the prescribed clotting factor replacement regimen will provide data on evolving treatment practices, including specific clotting factor replacement and non-factor products.
  • Report on the number of transient inhibitor, e.g., those which resolve without change in therapy [ Time Frame: 6 years ]
    The CDC is acting as the central laboratory for inhibitor testing. The CDC will report results to the participating HTC. If a blood specimen from a participant has an elevated result; potentially indicating the development of an inhibitor, a new blood specimen from the participant will be tested within 10 days of the first elevated result to determine if an inhibitor has developed. A transient inhibitor is defined as a positive inhibitor which is not confirmed on a consecutive repeat testing. Inhibitor testing results on all participants will be documented and reported by the HTC.
  • Report on targeted post-approval safety data for events related to clotting factor replacement products used by prospectively enroll participants [ Time Frame: 6 years ]
    Documentation of adverse events experienced by prospectively enrolled participants during the study period of first 50 exposure days to clotting factor replacement product will be reported. The types of adverse events to be reported are limited to Serious Adverse Events as defined by the European Union Haemophilia Safety Surveillance System (EUHASS).
  • Sub-study modules will be developed to evaluate and report on cohorts of study participants who initiated treatment with a specific product [ Time Frame: 6 years ]
    Measure the number of participants who initiate treatment with a specific treatment product
Original Secondary Outcome Measures
 (submitted: January 24, 2019)
  • Determine risk factors of inhibitor development in PUPs [ Time Frame: 6 years ]
    Data collection on all participants will include demographics, medical history, family history, birth history, detailed treatment history, and genetic testing result (if known).
  • Determine percentage of eligible participants enrolled at each site [ Time Frame: 6 years ]
    Sites will report number of eligible participants and number of participants enrolled to determine the percentage of enrollment.
  • Determine mean age of diagnosis and first exposure to factor treatment product [ Time Frame: 6 years ]
    Sites will document the date of diagnosis and the date of first exposure to clotting factor treatment product.
  • Determine the number of exposure days prior to inhibitor development [ Time Frame: 6 years ]
    Sites and participants will work together to provide detailed records of exposure days to clotting factor replacement products. The CDC will act as the central laboratory for the study and provide inhibitor testing.
  • Report bleeding complications that occur within the first 50 ED [ Time Frame: 6 years ]
    The documentation of bleeding events in the study records will be based on the review of bleeding and infusion records provided by the participant or the from medical chart review during the first 50 exposure days to clotting factor replacement product.
  • Summarize factor replacement dosing regimen prescribed to this study population within the first 50 ED [ Time Frame: 6 years ]
    A summary of the prescribed clotting factor replacement regimen will provide data on evolving treatment practices, including specific clotting factor replacement and non-factor products.
  • Determine the number of transient inhibitor, e.g., those which resolve without change in therapy [ Time Frame: 6 years ]
    The CDC will provide the inhibitor testing and report the results to the participating HTC. A transient inhibitor is defined as a positive inhibitor which is not confirmed on a consecutive repeat testing. All inhibitor testing results will be documented by the HTC on all participants.
  • Report on targeted post-approval safety data for events related to clotting factor replacement products used by prospectively enroll participants [ Time Frame: 6 years ]
    Documentation of adverse events experienced by prospectively enrolled participants during the study period of first 50 exposure days to clotting factor replacement product will be reported. The types of adverse events to be reported are limited to Serious Adverse Events as defined by the European Union Haemophilia Safety Surveillance System (EUHASS).
  • Sub-study modules will be developed to evaluate and report on cohorts of study participants who initiated treatment with a specific product [ Time Frame: 6 years ]
    Based on the main ATHN 8 Study, sub-studies on specific factor replacement products or non-factor products may be developed to report on specific areas of interest. Sub-studies may include a longer duration of follow-up (up to 100 ED), collect additional data element on specific product, and may require additional laboratory testing. Institutional Review Board (IRB) approval and consent will be obtained as appropriate to collect any additional data or measures not specified within this protocol.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title ATHN 8: PUPs Matter Study
Official Title US Cohort Study of Previously Untreated Patients (PUPs) With Congenital Hemophilia
Brief Summary This is a multi-center cohort study of approximately 250 previously untreated patients (PUPs) with congenital moderate to severe hemophilia A or B in a network of up to 50 US Hemophilia Treatment Centers (HTCs). Participants will be followed as they receive their first 50 exposure days (ED) to clotting factor replacement product, both prospectively and retrospectively. The data collected on evolving treatment practices will define the incidence and risk factors for inhibitor development during the high risk period of first 50 ED and improve the outcomes of this vulnerable population.
Detailed Description

This multi-center, longitudinal, observational, prospective and retrospective study of previously untreated patients (PUPs) with moderate to severe hemophilia A or B during the initial 50 exposure days (ED) to clotting factor replacement product or until the development of a confirmed inhibitor. The Primary Investigators have designed the study to utilize the American Thrombosis and Hemostasis Network (ATHN) electronic infrastructure to leverage existing data and enable the collection of more in-depth clinical and laboratory data on PUPs. The study aligns with the National Hemophilia Foundation Medical and Scientific Advisory Council (MASAC) recently issued Recommendation #243 which includes: "Regardless of which option is chosen, all PUPs should be enrolled in the ATHN data collection system or a clinical trial to assess outcomes." Co-enrollment in the ATHNdataset by participants is required. The total study duration is planned for 6 years.

The primary objective is to determine the percentage of patients with confirmed inhibitors within the first 50 ED. Confirmed inhibitors are defined as two consecutive positive inhibitor titers (per CDC laboratory criteria; >0.5 Nijmegen Bethesda Units for hemophilia A and >0.3 Nijmegen Bethesda Units for hemophilia B) on different blood samples which result in change in treatment recommendations.

Please note - the treatment regimen will be at the discretion of the participants' hemophilia caregivers. No treatment products are being provided by the study nor will the participants be paid. However, inhibitor titer testing will be provided at no cost to participants by the Centers for Disease Control and Prevention (CDC).

All study procedures and follow-up will be timed to coincide with scheduled hemophilia care whenever possible. Ad hoc, quarterly follow-up, annual and final visits are for participants who have not met study endpoints (50 ED or inhibitor development) prior to enrollment.

Data collected will include eligibility, demographics, medical history (co-morbidities, surgery/procedures, immunizations and allergies), hemophilia history (severity, genotype and family history), birth history, inhibitor testing results, detailed treatment product(s) usage, bleeding events, bleeding disorder related medical visits during the study, and EUHASS adverse events.

Sub-studies

A number of sub-studies are planned with pharmaceutical sponsors to collect information from patients about their specific product use. Participation in these product specific sub-studies is optional and sub-study visits will be planned to coincide with HTC visits. The sub-study will collect information from patients about their perception and use of treatment products, physical activity levels and other general health questions. This data will be collected via questionnaire.

Data Collection System

All data collected will be entered into electronic case report forms (eCRFs) within the secure ATHN System by HTC site personnel. All participating study sites will have in place a current, executed Data Use and Business Associate Agreement (DUBAA) with ATHN.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Other
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population The study will enroll a cohort of 250 participants born with hemophilia on or after January 1, 2010 who meet the eligibility criteria and are receiving care from one of the participating HTCs.
Condition
  • Hemophilia
  • Hemophilia A
  • Hemophilia B
  • Hemophilia A With Inhibitor
  • Hemophilia B With Inhibitor
  • Haemophilia B Without Inhibitor
  • Haemophilia A Without Inhibitor
  • Haemophilia
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: January 24, 2019)
250
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Congenital hemophilia A; FVIII </=5% or congenital hemophilia B; FIX </=5%;
  • Birth date on or after January 1, 2010;
  • Care established at one of the participating HTCs;
  • Co-enrollment in the ATHNdataset; and
  • Parent or authorized guardian can provide informed consent

Exclusion Criteria:

  • Patients who are referred to the HTC with no record of bleed and factor utilization data
Sex/Gender
Sexes Eligible for Study: All
Ages up to 13 Years   (Child)
Accepts Healthy Volunteers No
Contacts
Contact: Carol Fedor (800)-360-2846 ext 122 cfedor@athn.org
Contact: Carrie O'Neill (800)-360-2846 ext 124 coneill@athn.org
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03818529
Other Study ID Numbers ATHN 8
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party American Thrombosis and Hemostasis Network
Study Sponsor American Thrombosis and Hemostasis Network
Collaborators
  • CSL Behring
  • Octapharma
  • Takeda
Investigators
Principal Investigator: Shannon Carpenter, MD, MS Children's Mercy Hospital Kansas City
Principal Investigator: Courtney Thornburg, MD, MS University of California San Diego, Rady Children's Hospital San Diego
Principal Investigator: Marijke van den Berg, MD, PhD Versiti
PRS Account American Thrombosis and Hemostasis Network
Verification Date August 2020