Clinical trial NCT02502409: Natural History Study of Factor IX Treatment and Complications
Official title: Natural History Study of Factor IX Treatment and Complications
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Factor IX Deficiency
Keywords: Hemophilia B
Hemophilia B with Inhibitors
Lead sponsor: Skane University Hospital
Sponsor class: OTHER
Collaborators: name: Indiana Hemophilia &Thrombosis Center, Inc.
name: Bioverativ Therapeutics Inc.
name: Swedish Orphan Biovitrum
First posted: 2015-07-20
Enrollment: 550
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The population includes groups of two or more affected brothers, with or without a history of inhibitors, who share(d) one or both biological parents; and individuals with a history of an inhibitor. Most affected brother pairs will be concordant for no inhibitor and will serve as a control group for those with inhibitors. The study is open to subjects with mild (0.05-0.40 IU/mL), moderate (0.01-\<0.05 IU/mL), or severe (\<0.01 IU/mL) FIX deficiency. Females meeting the eligibility criteria may participate. There are no lower or upper age limits. Type of treatment, regimen, dosing and product(s) used are at the discretion of the investigator.

Brief summary: This study will examine two groups of subjects with factor IX (FIX) deficiency: 1) those with a current or history of inhibitors to FIX, and; 2) groups of two or more affected brothers, with or without inhibitors. The overall goal is to characterize the study groups in terms of their medical history, their patterns of bleeding, their care, quality of life, and complications including the development of joint disease, inhibitory antibodies to FIX, use of immune tolerance induction (ITI) and outcome.

Detailed description: Hemophilia B, FIX deficiency, is the second most common type of hemophilia, occurring in about one in 25,000 male births. This disease is in some ways more complex than hemophilia A, and is less well understood. Differences include a lower incidence and a greater risk of side effects to treatment, for example, allergic reactions and kidney disease. This study will examine two groups of subjects with FIX deficiency - those with a current or history of inhibitors to FIX, and groups of two or more affected brothers, with or without inhibitors. The overall goal is to characterize the study group in terms of their medical history, their patterns of bleeding, their care, quality of life, and complications including the development of inhibitory antibodies to FIX, allergies, kidney, and joint disease.

Eligibility criteria: Inclusion Criteria:

1. A consent approved by the appropriate Institutional Review Board (IRB)/Independent Ethics Committee (IEC) has been obtained from the subject or his legally acceptable representative
2. Subject has FIX deficiency AND

   * Is part of an affected brother pair/group that will also enroll; AND/OR
   * Has a current or history of inhibitor, defined as \>0.6 Bethesda units (BU)

Exclusion Criteria:

1. Subject has another congenital bleeding disorder
2. Subject is a carrier of hemophilia B with factor level \>0.40 IU/mL

Primary outcomes:
measure: Inhibitory antibodies
timeFrame: Baseline
measure: Annualized bleeding rate
timeFrame: 6 months
measure: Joint assessment
timeFrame: Baseline
measure: Renal disorders
timeFrame: 6 months
measure: Hemophilia treatment adherence
timeFrame: Baseline
measure: Health related quality of life
timeFrame: Baseline
measure: Non-inhibitory antibodies
timeFrame: Baseline
Secondary outcomes:
measure: Factor IX usage
timeFrame: 6 months
measure: Number of hospitalizations
timeFrame: 6 months
measure: Number of surgical procedures
timeFrame: 6 months
measure: number of days missed from school or work
timeFrame: 6 months
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana Hemophilia & Thrombosis Center
state: Indiana
Study officials:
affiliation: Skåne University Hospital, Malmö
name: Erik Berntorp, MD, PhD
role: STUDY_DIRECTOR
affiliation: Indiana Hemophilia &Thrombosis Center, Inc.
name: Amy D Shapiro, MD
role: STUDY_DIRECTOR
affiliation: Skåne University Hospital, Malmö
name: Jan Astermark, MD, PhD
role: STUDY_DIRECTOR
affiliation: Phoenix Children's Hospital, Phoenix, AZ
name: Christine Knoll, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina Hemophilia Treatment Center, Chapel Hill, NC
name: Yasmina Abajas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Weill Cornell Medical College, New York, NY
name: Catherine McGuinn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, Pakistan
name: Munira Borhany, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Henry Ford Health System, Detroit, MI
name: Philip Kuriakose, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National University Hospital Copenhagen, Copenhagen, Denmark
name: Eva Funding, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Hemophilia Center, Boston, MA
name: Stacy Croteau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University, Atlanta, Georgia
name: Christine Kempton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospitals and Clinics of Minnesota, Minneapolis, MN
name: Susan Kearney, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cohen Children's Medical Center, New Hyde Park, NY
name: Suchitra Acharya, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Michigan State University, East Lansing, MI
name: Roshni Kulkarni, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Great Ormond Street Hospital for Children, London, UK
name: Raina Liesner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr. v Hauner Children's University Hospital, Munich, Germany
name: Christoph Bidlingmaier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Newark Beth Israel Medical Center, Newark, NJ
name: Alice J. Cohen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro Hospitalar de São João, Porto, Portugal
name: Manuela Carvalho, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh and Hemophilia Center of Western Pennsylvania, Pittburgh, PA US
name: Margaret Ragni, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Jude Children's Research Hospital, Memphis, TN US
name: Ulrike Reiss, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Munson Medical Center, Traverse City, MI, US
name: Michelle Witkop, DNP, FNP-BC
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
name: Katharina Holstein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH US
name: Cristina Tarango, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Bleeding and Clotting Disorders Institute, Peoria, IL US
name: Michael D Tarantino, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Clinic, Bonn
name: Johannes Oldenburg, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shapiro AD, Ragni MV, Borhany M, Abajas YL, Tarantino MD, Holstein K, Croteau SE, Liesner R, Tarango C, Carvalho M, McGuinn C, Funding E, Kempton CL, Bidlingmaier C, Cohen A, Oldenburg J, Kearney S, Knoll C, Kuriakose P, Acharya S, Reiss UM, Kulkarni R, Witkop M, Lethagen S, Donfield S, LeBeau P, Berntorp E, Astermark J. Natural history study of factor IX deficiency with focus on treatment and complications (B-Natural). Haemophilia. 2021 Jan;27(1):49-59. doi: 10.1111/hae.14139. Epub 2020 Dec 5.