Clinical trial NCT01652027: Hemophilia Inhibitor Previously Untreated Patient Study
Official title: Study of Immunologic Determinants of Inhibitor Development in Previously Untreated Patients With Hemophilia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemophilia A
Keywords: FVIII inhibitors
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: Rho, Inc.
name: Baxter Healthcare Corporation
First posted: 2012-07-27
Enrollment: 25
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: Patients with severe hemophilia A who have not previously been treated with Factor VIII concentrates.

Brief summary: Hemophilia A is a congenital bleeding disorder caused by deficiency of factor VIII (FVIII) and is treated by replacement therapy with FVIII concentrate. Approximately 30% of people with severe hemophilia A develop neutralizing antibodies, called FVIII inhibitors, which interfere with the function of FVIII concentrates. The reason that some, but not all, people with severe hemophilia A develop inhibitors is incompletely understood. Understanding individual and environmental risk factors is important to be able to prevent and possibly treat inhibitors. This study will look at individual and treatment characteristics in babies with severe hemophilia A who have not yet received treatment with FVIII (called Previously Untreated Patients, or PUPS). Subjects in the study will be asked to provide diaries of treatments, medications, and illnesses. Treatment will be directed by the subjects' physician, but all subjects will receive Advate, a third-generation recombinant FVIII product. Subjects will have blood drawn for laboratory tests, which include studies of the immune system and genetic studies of the FVIII mutation, before and 7-9 days after the first treatment with FVIII, and 5 days (+/-2 days) after the 5th, 10th, 20th, 30th, 40th, and 50th days of treatment with FVIII (exposure days). The duration of the study will be first 50 treatments or 3 years, whichever comes first.


Eligibility criteria: Inclusion Criteria:

* Severe hemophilia A with FVIII activity \< 1% normal
* Weight \> 3.5 kg at the time of baseline study evaluation
* Informed consent, approved by appropriate Institutional Review Board/Independent Ethics Committee, has been administered, signed, and dated

Exclusion Criteria:

* Prior exposure to clotting factor concentrates or blood products
* Other chronic disease
* Currently participating in another investigational drug study.

Primary outcomes:
measure: Total number of FOXP3-positive T regulatory cells in the circulation
timeFrame: 50 exposure days to FVIII or 3 years, whichever comes first
Secondary outcomes:
measure: FVIII-specific T-cells
timeFrame: 50 exposure days to FVIII or 3 years, whichever comes first
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: New York
country: United States
facility: Cornell University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Portland
country: United States
facility: University of Oregon
state: Oregon
city: Pittsburgh
country: United States
facility: Hemophilia Center of Western Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: North Texas Comprehensive Hemophilia Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center-Houston
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain Hemophilia and Thrombosis Center
state: Utah
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Milan
country: Italy
facility: Angelo Bianchi Bonomi Hemophilia & Thrombosis Center
city: Amsterdam
country: Netherlands
facility: Emma Children's Hospital AMC
city: Malmo
country: Sweden
facility: Malmo Centre for Thrombosis and Haemostasis
Study officials:
affiliation: Maggiore Hospital and University of Milan
name: Elena Santagostino, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Paul H, Berg V, Gangadharan B, Bowen J, LeBeau P, Blatny J, Male C, Radulescu VC, Diaz R, Mancuso ME, Brown DL, Reipert BM. Prospective Hemophilia Inhibitor PUP Study reveals distinct antibody signatures during FVIII inhibitor eradication. Blood Adv. 2023 May 9;7(9):1831-1848. doi: 10.1182/bloodadvances.2022007267.
citation: Reipert BM, Gangadharan B, Hofbauer CJ, Berg V, Schweiger H, Bowen J, Blatny J, Fijnvandraat K, Mullins ES, Klintman J, Male C, McGuinn C, Meeks SL, Radulescu VC, Ragni MV, Recht M, Shapiro AD, Staber JM, Yaish HM, Santagostino E, Brown DL. The prospective Hemophilia Inhibitor PUP Study reveals distinct antibody signatures prior to FVIII inhibitor development. Blood Adv. 2020 Nov 24;4(22):5785-5796. doi: 10.1182/bloodadvances.2020002731.