Clinical trial NCT03619863: ATHN 7: Hemophilia Natural History Study
Official title: A Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment for People With Hemophilia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemophilia A With Inhibitor
Haemophilia A Without Inhibitor
Hemophilia B With Inhibitor
Haemophilia B Without Inhibitor
Keywords: Hemophilia
Non-Factor Products
Bypassing Agents
Clotting Factor Replacement Products
Lead sponsor: American Thrombosis and Hemostasis Network
Sponsor class: NETWORK
Collaborators: name: Genentech, Inc.
First posted: 2018-08-08
Enrollment: 395
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will enroll approximately 280 patients with hemophilia who meet the eligibility criteria and receiving care from one of the ATHN-affiliated Hemophilia Treatment Centers (HTC).

Brief summary: This is a real-world study of the safety of the treatments used for people with hemophilia. The study will follow people with hemophilia A or B from across the country for about 4 years as they receive treatment. The hemophilia treatment center (HTC) physician and participant will decide on the FDA-approved treatment to be used which may include non-factor products, bypassing agents, or clotting factor replacement products. The goal of this research is to study the use of hemophilia treatment products and their outcomes.

Detailed description: This non-interventional, minimal risk cohort study will enroll and follow patients with hemophilia A or B as they receive hemophilia treatment for 4 years. This is a pragmatic study of real-world practices across a wide range of patients which will be ongoing as new treatment products receive FDA approval and will be advantageous to the entire hemophilia community. The total study duration is planned for 6 years.

The patients are seen at baseline, annually, and at study exit. Patients will also receive routine quarterly follow-up phone calls from HTC staff to review medical history, bleed events, and product treatment history. Other visits for unplanned events or for the change of treatment product will be scheduled as necessary. All required study visits will be planned to coincide with routine clinical care whenever possible. Co-enrollment in the ATHNdataset by patients is required to participate in the study.

Please note - the treatment regimen will be at the discretion of the patients' 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 patients by the Center for Disease Control and Prevention (CDC).

The primary objective is to determine the safety of non-factor products, bypassing agents or clotting factor replacement products when used for people with hemophilia with or without inhibitors. Safety will be measured by those events listed in the European Haemophilia Safety Surveillance (EUHASS).

Data collected will include eligibility, demographics, medical history, hemophilia history (genotype and family history), inhibitor history and immune tolerance induction (ITI) treatment regimen (if applicable), co-morbidities at baseline (i.e., HIV, Hepatitis C), detailed treatment product(s) usage, bleeding events, surgical procedures, and EUHASS adverse events and other adverse events of special interest. Data collection will also include patient-reported outcome questionnaires regarding health-related quality of life, treatment use and patient perceptions of treatment products.

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 sub-studies (Product Specific Modules) is optional and sub-study visits will be planned to coincide with HTC visits. The modules 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:

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;
2. Able to give informed consent (by patient or parent/authorized guardian); and
3. Co-enrollment in the ATHNdataset.

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 Von Willebrand disease (VWD) diagnosis is not excluded); and
3. Unable or unwilling to comply with the study protocol.

Primary outcomes:
measure: Safety of treatment products used for hemophilia care will be assessed based on the number of reportable European Haemophilia Safety Surveillance (EUHASS) events documented on the ATHN Adverse Event Module Form.
timeFrame: 6 years
Secondary outcomes:
measure: Effectiveness of non-factor products, bypassing agents and clotting factor replacement products will be evaluated based on the participant's number of bleeding events reported as the annualized bleeding rate (ABR).
timeFrame: 6 years
measure: Dosing regimens for hemophilia treatment products and total amount utilized by the study participant for prophylaxis and treatment of bleeds will be assessed.
timeFrame: 6 years
measure: Target joint monitoring
timeFrame: 6 years
measure: Efficacy of treatment is rated by health-related outcomes tools: EQ-5D-5L, Patient-Reported Outcomes Measurement Information System (PROMIS), Global Adherence Rating (GAR), and Treatment Satisfaction with Medicines Questionnaire (SATMED-Q).
timeFrame: 6 years
measure: Real world effectiveness of treatment products assessed by the healthcare providers as measure by the number and types of medical visits and/or hospitalizations per year.
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: Los Angeles
country: United States
facility: Orthopaedic Institute for Children HTC
state: California
city: Los Angeles
country: United States
facility: Orthopedic Institute for Children Hemophilia Program
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: Aurora
country: United States
facility: Hemophilia and Thrombosis Center/ University of Colorado Anschutz Medical Campus
state: Colorado
city: Gainesville
country: United States
facility: University of Florida Hemophilia Treatment Center
state: Florida
city: Atlanta
country: United States
facility: Comprehensive Bleeding Disorders Center at Emory University and Children's Healthcare of Atlanta
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: New Orleans
country: United States
facility: Louisiana Center for Bleeding and Clotting Disorders, Tulane University
state: Louisiana
city: New Orleans
country: United States
facility: Louisiana Center for Bleeding and Clotting Disorders
state: Louisiana
city: Scarborough
country: United States
facility: Maine Hemophilia and Thrombosis Center
state: Maine
city: Boston
country: United States
facility: Massachusetts General Hospital Comprehensive Hemophilia and Thrombosis Treatment Center
state: Massachusetts
city: East Lansing
country: United States
facility: Michigan State University Center for Bleeding and Clotting Disorders
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: The John Bouhasin Center for Children with Bleeding Disorders
state: Missouri
city: Las Vegas
country: United States
facility: Hemostasis and Thrombosis Center of Nevada
state: Nevada
city: Reno
country: United States
facility: Hemostasis and Thrombosis Center of Nevada
state: Nevada
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Science
state: North Carolina
city: Toledo
country: United States
facility: Northwest Ohio Hemophilia Treatment Center at the Toledo Hospital
state: Ohio
city: Portland
country: United States
facility: The Hemophilia Center at Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia (CHOP)
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Comprehensive Hemophilia and Thrombophilia Program/Hospital of the University of Pennsylvania
state: Pennsylvania
city: Memphis
country: United States
facility: St Jude Children's Research Hospital
state: Tennessee
city: Dallas
country: United States
facility: The Center for Cancer and Blood Disorders, Children's Medical Center of Dallas
state: Texas
city: Houston
country: United States
facility: Gulf States Hemophilia and Thrombosis Center
state: Texas
city: Milwaukee
country: United States
facility: Comprehensive Center for Bleeding Disorders
state: Wisconsin
Study officials:
affiliation: Hemophilia and Thrombosis Center/ University of Colorado Anschutz Medical Campus
name: Tyler Buckner, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: The Hemophilia Center at Oregon Health & Science University
name: Michael Recht, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ragni MV. Targeting Antithrombin to Treat Hemophilia. N Engl J Med. 2015 Jul 23;373(4):389-91. doi: 10.1056/NEJMcibr1505657. No abstract available.
citation: Gouw SC, van den Berg HM, Fischer K, Auerswald G, Carcao M, Chalmers E, Chambost H, Kurnik K, Liesner R, Petrini P, Platokouki H, Altisent C, Oldenburg J, Nolan B, Garrido RP, Mancuso ME, Rafowicz A, Williams M, Clausen N, Middelburg RA, Ljung R, van der Bom JG; PedNet and Research of Determinants of INhibitor development (RODIN) Study Group. Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study. Blood. 2013 May 16;121(20):4046-55. doi: 10.1182/blood-2012-09-457036. Epub 2013 Apr 3.
citation: Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, Fukazawa N, Yoneyama K, Yoshida H, Nogami K. Factor VIII-Mimetic Function of Humanized Bispecific Antibody in Hemophilia A. N Engl J Med. 2016 May 26;374(21):2044-53. doi: 10.1056/NEJMoa1511769.
citation: Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, Santagostino E, Kruse-Jarres R, Negrier C, Kessler C, Valente N, Asikanius E, Levy GG, Windyga J, Shima M. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med. 2017 Aug 31;377(9):809-818. doi: 10.1056/NEJMoa1703068. Epub 2017 Jul 10.
citation: Carr ME, Tortella BJ. Emerging and future therapies for hemophilia. J Blood Med. 2015 Sep 3;6:245-55. doi: 10.2147/JBM.S42669. eCollection 2015.
citation: Sehgal A, Barros S, Ivanciu L, Cooley B, Qin J, Racie T, Hettinger J, Carioto M, Jiang Y, Brodsky J, Prabhala H, Zhang X, Attarwala H, Hutabarat R, Foster D, Milstein S, Charisse K, Kuchimanchi S, Maier MA, Nechev L, Kandasamy P, Kel'in AV, Nair JK, Rajeev KG, Manoharan M, Meyers R, Sorensen B, Simon AR, Dargaud Y, Negrier C, Camire RM, Akinc A. An RNAi therapeutic targeting antithrombin to rebalance the coagulation system and promote hemostasis in hemophilia. Nat Med. 2015 May;21(5):492-7. doi: 10.1038/nm.3847. Epub 2015 Apr 13.