ATHN 2: Factor Switching Study
A Longitudinal, Observational Study of Previously Treated Hemophilia Patients Switching Factor Replacement Products
1 other identifier
observational
310
1 country
27
Brief Summary
This is a longitudinal, observational study of patients with Hemophilia A or B who are planning to switch to a newly approved coagulation factor replacement product, or who have recently switched factor products. The study will follow each patient for up to 1 year. Patients will be recruited at Hemophilia Treatment Centers (HTC) which are ATHN-affiliates. The primary outcome being studied is the development of inhibitor (i.e., antibodies to factor) at 1 year or 50 exposure days, whichever comes first. The study will be conducted at approximately 30 HTCs, with a planned enrollment of 600 patients.The entire study duration is projected to be approximately 6 years. In addition, optional substudies will be included for some products, as "Product-Specific Modules". These will be questionnaires to collect data for subjects receiving selected Factor products. For example, subjects receiving Kovaltry will be approached to participate in the 'Kovaltry Product-Specific Module'; subjects receiving Adynovate will be approached to participate in the 'Adynovate Product-Specific Module'. Questions will be related to product use, perceptions of product use, and other post-marketing consumer data.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Sep 2015
Longer than P75 for all trials
27 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2015
CompletedFirst Submitted
Initial submission to the registry
September 9, 2015
CompletedFirst Posted
Study publicly available on registry
September 11, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2020
CompletedDecember 9, 2021
August 1, 2020
4.8 years
September 9, 2015
December 7, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Inhibitor Development
Inhibitor development is the primary outcome. Subjects will be followed closely and tested at baseline, after 10 Exposure Days and 50 Exposure Days, and/or at 1 year. Specimens will be submitted to local laboratories and evaluated for inhibitor titers, and inhibitors will be confirmed by local laboratories and CDC.
After 50 Exposure Days or 1 Year, whichever comes first
Secondary Outcomes (4)
Inhibitor Development
10 days
Prevalence of risk factors for inhibitor development
1 year
Targeted post-marketing approval safety and efficacy data
1 year
Platform for additional substudies
1 year
Study Arms (2)
Arm A Prospective
Patients who are switching to a new Factor VIII and Factor IX Replacement Product for Hemophilia A and B which was FDA approved after January 1, 2013. These patients will be followed prospectively for up to 1 year.
Arm B Retrospective
Patients who have recently switched to a new Factor VIII and Factor IX Replacement Product for Hemophilia A and B which was FDA approved after January 1, 2013. Patients must have switched products within the past 50 weeks at the time of enrollment. These patients will be assessed retrospectively and/or followed prospectively for up to 1 year.
Interventions
Prophylaxis for prevention of bleeding, various regimens.
Prophylaxis for prevention of bleeding, various regimens.
Eligibility Criteria
The study will enroll approximately 600 patients with hemophilia who meet the eligibility criteria and are receiving care from one of the ATHN-affiliated Hemophilia Treatment Centers (HTC). There will be 2 arms: Arm A (Prospective) will include patients who are switching factor replacement products and will be followed prospectively for up to 1 year. Arm B (Retrospective) will include patients who have switched factor replacement products previously (within the past 50 weeks at the time of enrollment). These patients will be assessed retrospectively and/or followed prospectively for up to 1 year.
You may qualify if:
- Moderate or Severe Congenital Hemophilia A or B (FVIII or FIX clotting activity less than or equal to 5% of normal).
- Able to give informed consent (by patient or parent/authorized guardian).
- Previously treated with plasma-derived or recombinant clotting factor replacement products with at least 50 exposure days (as assessed either from direct clinical records in children under age 5, or by clinical history of dosing in older patients). For Arm B being enrolled retrospectively, this previous treatment must be prior to product switch under study.
- Planning to switch, or recently switched within the previous 50 weeks, to a new brand or type of replacement factor VIII or IX, FDA approved after January 1, 2013.
- Arm B only: Negative inhibitor screen within the last 6 months prior to switching.
- Note: History of prior transient inhibitor or inhibitor eradicated by immune tolerance induction (ITI) are eligible.
You may not qualify if:
- Presence of any known bleeding disorder other than hemophilia A or B (i.e., patients with concurrent hemophilia and a second hemostatic defect are NOT eligible). Low Von Willebrand Factor (VWF) without VWF diagnosis are not excluded.
- Presence of an active inhibitor \>0.6 BU for factor VIII, \> 0.4 BU for factor IX at the time of eligibility assessment. Detection of such an inhibitor at the baseline visit prior to dosing with the new product (Arm A), or after dosing with new factor dosing (Arm B), would result in early termination without other study assessments.
- Currently undergoing ITI.
- Immunosuppressive therapy (cyclophosphamide, mycophenolate, IVIG) within 90 days and Rituximab within 6 months; topical steroid treatments and short course steroids for asthma or allergy allowed.
- Previous participation in Phase I, II or III interventional trials of the factor product being switched to.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- American Thrombosis and Hemostasis Networklead
- Shirecollaborator
- CSL Behringcollaborator
- Bioverativ Therapeutics Inc.collaborator
- Bayercollaborator
Study Sites (27)
University of California San Diego (UCSD)
San Diego, California, 92122, United States
University of Colorado Denver Hemophilia and Thrombosis Center
Aurora, Colorado, 80045, United States
Yale Hemophilia Treatment Center
New Haven, Connecticut, 06520, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701, United States
St. Joseph's Children's Hospital
Tampa, Florida, 33607, United States
Children's Healthcare of Atlanta/Emory
Atlanta, Georgia, 30322, United States
Bleeding and Clotting Disorders Institute
Peoria, Illinois, 61615, United States
Indiana Hemophilia and Thrombosis Center (IHTC)
Indianapolis, Indiana, 46260, United States
Louisiana Center for Bleeding and Clotting Disorders
New Orleans, Louisiana, 70112, United States
Maine Hemophilia and Thrombosis Center
Scarborough, Maine, 04074, United States
Johns Hopkins University Medical Center
Baltimore, Maryland, 21205, United States
Boston Hemophilia Center at Children's Hospital of Boston
Boston, Massachusetts, 02115, United States
University of Michigan Hemophilia and Coagulation Disorders Program
Ann Arbor, Michigan, 48109, United States
Michigan State University Center for Bleeding and Clotting Disorders
East Lansing, Michigan, 48823, United States
Children's Mercy Hospital
Kansas City, Missouri, 64108, United States
Dartmouth-Hitchcock Comprehensive Hemophilia and Thrombosis Center
Lebanon, New Hampshire, 03756, United States
Weill Cornell Medicine
New York, New York, 10065, United States
Mary M. Gooley Hemophilia Center
Rochester, New York, 14621, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, 19104, United States
Pennsylvania Comprehensive Hemophilia and Thrombophilia Program / Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
The Hemophilia Center of Western Pennsylvania
Pittsburgh, Pennsylvania, 15213, United States
St Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
UTSW Medical Center at Dallas/Children's Medical Center
Dallas, Texas, 75235, United States
Washington Center for Bleeding Disorders Bloodworks Northwest d/b/a Puget Sound Blood Center
Seattle, Washington, 98104, United States
Blood Center of Wisconsin
Milwaukee, Wisconsin, 53201, United States
Related Publications (5)
Josephson CD, Abshire T. The new albumin-free recombinant factor VIII concentrates for treatment of hemophilia: do they represent an actual incremental improvement? Clin Adv Hematol Oncol. 2004 Jul;2(7):441-6.
PMID: 16163220BACKGROUNDPowell JS. Lasting power of new clotting proteins. Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):355-63. doi: 10.1182/asheducation-2014.1.355. Epub 2014 Nov 18.
PMID: 25696879BACKGROUNDRagni, MV, Kessler, CM, and Lozier, JN (2009). Clinical aspects and therapy for hemophilia, in Hoffman R, Benz EJ, Shattil, SJ et al eds, Hematology, Basic Principles and Practice, 5th Edition, Churchill Livingstone, Philadelphia, pp 1911-1930.
BACKGROUNDAbshire TC, Brackmann HH, Scharrer I, Hoots K, Gazengel C, Powell JS, Gorina E, Kellermann E, Vosburgh E. Sucrose formulated recombinant human antihemophilic factor VIII is safe and efficacious for treatment of hemophilia A in home therapy--International Kogenate-FS Study Group. Thromb Haemost. 2000 Jun;83(6):811-6.
PMID: 10896230BACKGROUNDMahlangu J, Powell JS, Ragni MV, Chowdary P, Josephson NC, Pabinger I, Hanabusa H, Gupta N, Kulkarni R, Fogarty P, Perry D, Shapiro A, Pasi KJ, Apte S, Nestorov I, Jiang H, Li S, Neelakantan S, Cristiano LM, Goyal J, Sommer JM, Dumont JA, Dodd N, Nugent K, Vigliani G, Luk A, Brennan A, Pierce GF; A-LONG Investigators. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood. 2014 Jan 16;123(3):317-25. doi: 10.1182/blood-2013-10-529974. Epub 2013 Nov 13.
PMID: 24227821BACKGROUND
Biospecimen
Plasma drawn at baseline, after 10 Exposure Days, after 50 Exposure Days, and at study end (1 year). If inhibitor suspected, sample will be drawn and tested locally, and within 2 weeks of first positive inhibitor, a confirmatory sample will be drawn and sent to CDC. Patients may be co-enrolled in other ATHN studies such as My Life Our Future, will performs genotype Samples may be linked in patient who have authorized
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ellis J Neufeld, MD, PhD
St. Jude Children's Research Hospital
- PRINCIPAL INVESTIGATOR
Janna Journeycake, MD
Oklahoma Center for Bleeding and Clotting Disorders
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- OTHER
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 9, 2015
First Posted
September 11, 2015
Study Start
September 1, 2015
Primary Completion
June 30, 2020
Study Completion
June 30, 2020
Last Updated
December 9, 2021
Record last verified: 2020-08
Data Sharing
- IPD Sharing
- Will share
Product-Specific Module data for subjects enrolled in each module will be shared with each sponsor, as appropriate.