Clinical trial NCT03818529: ATHN 8: Previously Untreated Patients (PUPs) Matter Study
Official title: US Cohort Study of Previously Untreated Patients (PUPs) With Congenital Hemophilia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemophilia
Hemophilia A
Hemophilia B
Hemophilia A With Inhibitor
Hemophilia B With Inhibitor
Haemophilia B Without Inhibitor
Haemophilia A Without Inhibitor
Haemophilia
Keywords: Hemophilia
Previously Untreated Patients (PUPs)
Clotting Factor Replacement Products
Haemophilia
Lead sponsor: American Thrombosis and Hemostasis Network
Sponsor class: NETWORK
Collaborators: name: CSL Behring
name: Octapharma
name: Takeda
First posted: 2019-01-28
Enrollment: 237
Sex: ALL
Minimum age (years): 0
Maximum age (years): 13
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
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.

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.

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

Primary outcomes:
measure: Determine percentage of patients with confirmed inhibitors
timeFrame: 6 years
Secondary outcomes:
measure: Determine risk factors including genetic variants associated with inhibitor development in PUPs
timeFrame: 6 years
measure: Determine percentage of eligible participants enrolled at each site
timeFrame: 6 years
measure: Determine mean age of diagnosis and first exposure to factor treatment product
timeFrame: 6 years
measure: Determine the number of exposure days prior to inhibitor development
timeFrame: 6 years
measure: Report bleeding complications that occur within the first 50 ED
timeFrame: 6 years
measure: Summarize factor replacement dosing regimen prescribed to this study population within the first 50 ED
timeFrame: 6 years
measure: Report on the number of transient inhibitor, e.g., those which resolve without change in therapy
timeFrame: 6 years
measure: Report on targeted post-approval safety data for events related to clotting factor replacement products used by prospectively enroll participants
timeFrame: 6 years
measure: Sub-study modules will be developed to evaluate and report on cohorts of study participants who initiated treatment with a specific product
timeFrame: 6 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Hemophilia and Thrombosis Center at Phoenix Children's Hospital
state: Arizona
city: Madera
country: United States
facility: Valley Children's Hospital
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Pediatric Hemophilia Treatment Center at Mission Bay
state: California
city: Aurora
country: United States
facility: University of Colorado Denver Hemophilia and Thrombosis Center
state: Colorado
city: Farmington
country: United States
facility: Connecticut Bleeding and Clotting Disorders Center
state: Connecticut
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta/Emory
state: Georgia
city: Augusta
country: United States
facility: Augusta University Hemophilia Treatment Center
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center (IHTC)
state: Indiana
city: Kansas City
country: United States
facility: Kansas City Regional Hemophilia Center
state: Kansas
city: Scarborough
country: United States
facility: Maine Hemophilia and Thrombosis Center
state: Maine
city: Boston
country: United States
facility: Boston Hemophilia Center at Children's Hospital of Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hemophilia and Coagulation Disorders
state: Michigan
city: Rochester
country: United States
facility: Mayo Comprehensive Hemophilia Center
state: Minnesota
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center, Hemophilia & Thrombosis Center
state: Ohio
city: Cleveland
country: United States
facility: UHHS Cleveland
state: Ohio
city: Toledo
country: United States
facility: Northwest Ohio Hemophilia Treatment Center at the Toledo Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Center for Bleeding and Clotting Disorders
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Memphis
country: United States
facility: St Jude Children's Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Salt Lake City
country: United States
facility: Utah Center for Bleeding & Clotting Disorders at Primary Children's Hospital
state: Utah
city: Green Bay
country: United States
facility: Hemophilia Outreach Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Blood Center of Wisconsin
state: Wisconsin
Study officials:
affiliation: Children's Mercy Hospital Kansas City
name: Shannon Carpenter, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California San Diego, Rady Children's Hospital San Diego
name: Courtney Thornburg, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Versiti
name: Marijke van den Berg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: