ATHN 8: Previously Untreated Patients (PUPs) Matter Study

Hemophilia A Clinical Trial

Official title:

US Cohort Study of Previously Untreated Patients (PUPs) With Congenital Hemophilia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03818529
• Other study ID #: ATHN 8
• Status: Completed
• Start date: October 3, 2018
• Est. completion date: December 31, 2022

Study information

• Verified date: January 2023
• Source: American Thrombosis and Hemostasis Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 237
• Est. completion date: December 31, 2022
• Est. primary completion date: January 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 13 Years

Eligibility

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

Related Conditions & MeSH terms

• Haemophilia
• Haemophilia A Without Inhibitor
• Haemophilia B Without Inhibitor
• Hemophilia
• Hemophilia A
• Hemophilia A With Inhibitor
• Hemophilia B
• Hemophilia B With Inhibitor

Locations

Country	Name	City	State
United States	University of Michigan Hemophilia and Coagulation Disorders	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta/Emory	Atlanta	Georgia
United States	Augusta University Hemophilia Treatment Center	Augusta	Georgia
United States	University of Colorado Denver Hemophilia and Thrombosis Center	Aurora	Colorado
United States	Boston Hemophilia Center at Children's Hospital of Boston	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center, Hemophilia & Thrombosis Center	Cincinnati	Ohio
United States	UHHS Cleveland	Cleveland	Ohio
United States	Connecticut Bleeding and Clotting Disorders Center	Farmington	Connecticut
United States	Hemophilia Outreach Center	Green Bay	Wisconsin
United States	Indiana Hemophilia and Thrombosis Center (IHTC)	Indianapolis	Indiana
United States	Kansas City Regional Hemophilia Center	Kansas City	Kansas
United States	Valley Children's Hospital	Madera	California
United States	St Jude Children's Research Hospital	Memphis	Tennessee
United States	Blood Center of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Oklahoma Center for Bleeding and Clotting Disorders	Oklahoma City	Oklahoma
United States	Arizona Hemophilia and Thrombosis Center at Phoenix Children's Hospital	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	Mayo Comprehensive Hemophilia Center	Rochester	Minnesota
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida
United States	Utah Center for Bleeding & Clotting Disorders at Primary Children's Hospital	Salt Lake City	Utah
United States	Rady Children's Hospital San Diego	San Diego	California
United States	UCSF Pediatric Hemophilia Treatment Center at Mission Bay	San Francisco	California
United States	Maine Hemophilia and Thrombosis Center	Scarborough	Maine
United States	Northwest Ohio Hemophilia Treatment Center at the Toledo Hospital	Toledo	Ohio
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (4)

Lead Sponsor	Collaborator
American Thrombosis and Hemostasis Network	CSL Behring, Octapharma, Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine percentage of patients with confirmed inhibitors	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.	6 years
Secondary	Determine risk factors including genetic variants associated with inhibitor development in PUPs	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.	6 years
Secondary	Determine percentage of eligible participants enrolled at each site	Sites will report number of eligible participants and number of participants enrolled to determine the percentage of enrollment.	6 years
Secondary	Determine mean age of diagnosis and first exposure to factor treatment product	Sites will document the date of diagnosis and the date of first exposure to clotting factor treatment product.	6 years
Secondary	Determine the number of exposure days prior to inhibitor development	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.	6 years
Secondary	Report bleeding complications that occur within the first 50 ED	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.	6 years
Secondary	Summarize factor replacement dosing regimen prescribed to this study population within the first 50 ED	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.	6 years
Secondary	Report on the number of transient inhibitor, e.g., those which resolve without change in therapy	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.	6 years
Secondary	Report on targeted post-approval safety data for events related to clotting factor replacement products used by prospectively enroll participants	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).	6 years
Secondary	Sub-study modules will be developed to evaluate and report on cohorts of study participants who initiated treatment with a specific product	Measure the number of participants who initiate treatment with a specific treatment product	6 years