A Study of Factor XIII Concentrate in Subjects With Congenital Factor XIII Deficiency

A Prospective, Multicenter, Open-label, Phase 3b Study of Human Plasma-Derived Factor XIII Concentrate in Subjects With Congenital Factor XIII Deficiency

Congenital deficiency of factor XIII (FXIII) is an extremely rare inherited disorder associated with potentially life-threatening bleeding. Factor XIII Concentrate is given to patients whose blood is lacking factor XIII. Factor XIII Concentrate works by assisting blood in the usual clotting process, thereby preventing bleeding.

In this study, patients will be treated with FXIII Concentrate (Human) and followed closely to determine that they receive the dose that will best minimize the chance of bruising and bleeding.

Study Overview

• Status: Completed
• Conditions: Factor XIII Deficiency
• Intervention / Treatment: Biological: FXIII Concentrate (Human)

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Santa Cruz de Tenerife, Spain, 38009
    • Study Site
• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
      • Study Site
  • California
    • Oakland, California, United States, 94610
      • Study Site
    • Orange, California, United States, 92868
      • Study Site
    • San Francisco, California, United States, 94115
      • Study Site
    • Stockton, California, United States, 95204
      • Study Site
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Study Site
  • Florida
    • Fort Meyers, Florida, United States, 33908
      • Study Site
    • Miami, Florida, United States, 33136
      • study
  • Idaho
    • Boise, Idaho, United States, 83712
      • Study Site
  • Indiana
    • South Bend, Indiana, United States, 46601
      • Study Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Study Site
  • Minnesota
    • St. Paul, Minnesota, United States, 55102
      • Study Site
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Study Site
  • Nevada
    • Las Vegas, Nevada, United States, 89015
      • Study Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Study Site
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Study Site
  • New York
    • Albany, New York, United States, 12208
      • Study Site
    • New York, New York, United States, 10021
      • Study Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Study Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Study Site
  • Texas
    • Dallas, Texas, United States, 75390
      • Study Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53233
      • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent/assent for study participation obtained before undergoing any study-specific procedures
• Documented congenital FXIII deficiency which requires prophylactic treatment with a FXIII containing product.
• Males and females of any age with congenital FXIII deficiency
• Received full hepatitis B vaccination and/or is hepatitis B surface antibody positive

Exclusion Criteria:

• Diagnosis of acquired FXIII deficiency
• Administration of a FXIII-containing product, including blood transfusions or other blood products within 4 weeks prior to the planned Day 0
• Any known congenital or acquired coagulation disorder other than congenital FXIII deficiency
• Known or suspected to have antibodies towards FXIII
• Use of any other investigational medicinal product within 4 weeks prior to the Baseline Visit (Day 0)
• Known Positivity for human immunodeficiency virus (HIV) or a positive result for HIV at the Screening Visit of this study or the FXIII study 2002 (NCT00883090).
• Serum aspartate transaminase (AST) or serum alanine transaminase (ALT) concentration >2.5 times the upper limit of normal at the Screening Visit of this study or at the Day 56 Visit of Factor XIII Study BI71023_2002 (NCT00883090)
• Fibrinogen level less than 85% of the lower limit of normal at the Screening Visit of this study or the Factor XIII Study BI71023_2002 (NCT00883090)
• Active bleeding ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 and/or ≥ moderate between the Screening and Baseline Visits
• Pregnant or breast-feeding
• Intention to become pregnant during the course of the study
• Female subjects of childbearing potential not using, or not willing to use, a medically reliable method of contraception for the entire duration of the study
• Suspected inability (e.g., language problems) or unwillingness to comply with study procedures or history of noncompliance

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: FXIII; All subjects who received a dose of Factor XIII (FXIII) Concentrate (Human).

Biological: FXIII Concentrate (Human); Doses will be guided by the individual subject's most recent FXIII activity levels, with the objective of dosing every 28 days to maintain a trough FXIII activity level of approximately 5 to 20%. Subjects enrolled in this study who did not complete the pharmacokinetic study (Factor XIII Study BI71023_2002 [NCT00883090]) will initially receive FXIII Concentrate (Human) at a dose of 40 U/kg by intravenous (IV) infusion.; Other Names: Fibrogammin-P

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Incidence of Spontaneous Bleeding Events Requiring Treatment (Treatment is Defined as Administration of a FXIII-Containing Product to Treat the Bleeding Event)	The number of subjects requiring treatment with a Factor XIII-containing product to treat a spontaneous bleeding event.	Up to week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of the Incidence of Spontaneous Bleeding Events Requiring Treatment and FXIII Activity Trough Levels	P-value determined from Generalized Estimating Equation (GEE) model parameter estimates with bleeding as the response variable and FXIII activity trough level as the explanatory variable.	12 months
Adverse Events	Number of subjects with any treatment-emergent adverse event (AE), treatment-related AE or serious AE (SAE). Treatment related AEs are defined as AEs whose relationship to study treatment is related, or possibly related, and AEs with missing relationship.	12 months
Peak FXIII Concentration at Steady State		At 12, 24, 36 and 48 weeks: at 30 and 60 minutes after the end of the infusion.
Trough FXIII Concentration at Steady State		At 12, 24, 36 and 48 weeks: immediately before infusion.
Time to Peak Concentration		At 12, 24, 36 and 48 weeks: immediately before infusion, then at 30 and 60 minutes after the end of the infusion.
Incremental Recovery	Incremental recovery (U/mL/U/kg) is defined as maximum (peak) FXIII activity (U/mL) obtained after infusion, per dose of (U/kg) infusion.	At 12, 24, 36 and 48 weeks: immediately before infusion, then at 30 and 60 minutes after the end of the infusion.
Achievement of Trough Factor XIII Levels of 5% or Higher.	Number of subjects with Factor XIII level ≥ 5% before infusion at Week 12, Week 24, Week 36 and Week 48.	At 12, 24, 36 and 48 weeks: immediately before infusion.

Collaborators and Investigators

• Sponsor: CSL Behring

Publications and helpful links

General Publications

• Ashley C, Chang E, Davis J, Mangione A, Frame V, Nugent DJ. Efficacy and safety of prophylactic treatment with plasma-derived factor XIII concentrate (human) in patients with congenital factor XIII deficiency. Haemophilia. 2015 Jan;21(1):102-8. doi: 10.1111/hae.12524. Epub 2014 Nov 7.

Helpful Links

• Factor XIII Study BI71023_2002 (NCT00883090)
• Factor XIII Study BI71023_3002 (NCT00945906)

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: April 21, 2009
• First Submitted That Met QC Criteria: April 21, 2009
• First Posted (Estimate): April 22, 2009

Study Record Updates

• Last Update Posted (Estimate): July 16, 2012
• Last Update Submitted That Met QC Criteria: July 10, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Factor XIII; Hereditary Factor XIII deficiency
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Factor XIII Deficiency; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Fibrinolysin
• Other Study ID Numbers: BI71023_3001; 1482 (CSL Behring); 2009-010722-19 (EudraCT Number)